CLARITY Extension Study
A Phase IIIb, Double-Blind, Placebo-Controlled, Multicenter, Parallel Group, Extension Trial to Evaluate the Safety and Tolerability of Oral Cladribine in Subjects With Relapsing-Remitting Multiple Sclerosis Who Have Completed Trial 25643 (CLARITY)
What it found
Results posted, not judged
Results are posted in the registry, but without a statistical test of the main measure. See the numbers below.
What was tested
Treatment tested
- Cladribine
DNA inhibitor
Placebo
- Placebo
Results by group
Safety Population: Percentage of Participants With at Least 1 Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE) Grade 4 Hematologic and Hepatic Toxicity
Baseline up to Week 120
| Group | Value | Interval | Number analysed |
|---|---|---|---|
| Cladribine Low/Placebo (LLPP) | 0.0 percentage of participants | 98 | |
| Cladribine High Dose/Placebo (HLPP) | 0.0 percentage of participants | 92 | |
| Cladribine Low/Low Dose (LLLL) | 2.7 percentage of participants | 186 | |
| Cladribine High/Low Dose (HLLL) | 3.2 percentage of participants | 186 | |
| Placebo/Cladribine Low Dose (PPLL) | 0.4 percentage of participants | 244 | |
| Cladribine Low/Placebo (LLPP) | 0.0 percentage of participants | 98 | |
| Cladribine High Dose/Placebo (HLPP) | 0.0 percentage of participants | 92 | |
| Cladribine Low/Low Dose (LLLL) | 0.0 percentage of participants | 186 | |
| Cladribine High/Low Dose (HLLL) | 0.0 percentage of participants | 186 | |
| Placebo/Cladribine Low Dose (PPLL) | 0.0 percentage of participants | 244 | |
| Cladribine Low/Placebo (LLPP) | 0.0 percentage of participants | 98 | |
| Cladribine High Dose/Placebo (HLPP) | 0.0 percentage of participants | 92 | |
| Cladribine Low/Low Dose (LLLL) | 0.5 percentage of participants | 186 | |
| Cladribine High/Low Dose (HLLL) | 0.0 percentage of participants | 186 | |
| Placebo/Cladribine Low Dose (PPLL) | 0.0 percentage of participants | 244 | |
| Cladribine Low/Placebo (LLPP) | 0.0 percentage of participants | 98 | |
| Cladribine High Dose/Placebo (HLPP) | 2.2 percentage of participants | 92 | |
| Cladribine Low/Low Dose (LLLL) | 0.5 percentage of participants | 186 | |
| Cladribine High/Low Dose (HLLL) | 0.0 percentage of participants | 186 | |
| Placebo/Cladribine Low Dose (PPLL) | 0.4 percentage of participants | 244 | |
| Cladribine Low/Placebo (LLPP) | 0.0 percentage of participants | 98 | |
| Cladribine High Dose/Placebo (HLPP) | 0.0 percentage of participants | 92 | |
| Cladribine Low/Low Dose (LLLL) | 0.5 percentage of participants | 186 | |
| Cladribine High/Low Dose (HLLL) | 0.0 percentage of participants | 186 | |
| Placebo/Cladribine Low Dose (PPLL) | 0.0 percentage of participants | 244 | |
| Cladribine Low/Placebo (LLPP) | 0.0 percentage of participants | 98 | |
| Cladribine High Dose/Placebo (HLPP) | 0.0 percentage of participants | 92 | |
| Cladribine Low/Low Dose (LLLL) | 0.0 percentage of participants | 186 | |
| Cladribine High/Low Dose (HLLL) | 0.0 percentage of participants | 186 | |
| Placebo/Cladribine Low Dose (PPLL) | 0.0 percentage of participants | 244 | |
| Cladribine Low/Placebo (LLPP) | 0.0 percentage of participants | 98 | |
| Cladribine High Dose/Placebo (HLPP) | 0.0 percentage of participants | 92 | |
| Cladribine Low/Low Dose (LLLL) | 0.0 percentage of participants | 186 | |
| Cladribine High/Low Dose (HLLL) | 0.0 percentage of participants | 186 | |
| Placebo/Cladribine Low Dose (PPLL) | 0.0 percentage of participants | 244 | |
| Cladribine Low/Placebo (LLPP) | 0.0 percentage of participants | 98 | |
| Cladribine High Dose/Placebo (HLPP) | 0.0 percentage of participants | 92 | |
| Cladribine Low/Low Dose (LLLL) | 0.0 percentage of participants | 186 | |
| Cladribine High/Low Dose (HLLL) | 0.0 percentage of participants | 186 | |
| Placebo/Cladribine Low Dose (PPLL) | 0.0 percentage of participants | 244 |
Safety Population: Mean Change From Baseline in Absolute Lymphocyte Count, Platelet, Neutrophils and Leukocytes at Week 120
Baseline, Week 120
| Group | Value | Interval | Number analysed |
|---|---|---|---|
| Cladribine Low/Placebo (LLPP) | 0.3 10^9 cells per liter | 0.4 (Standard Deviation) | 73 |
| Cladribine High Dose/Placebo (HLPP) | 0.3 10^9 cells per liter | 0.4 (Standard Deviation) | 62 |
| Cladribine Low/Low Dose (LLLL) | 0.0 10^9 cells per liter | 0.4 (Standard Deviation) | 137 |
| Cladribine High/Low Dose (HLLL) | 0.0 10^9 cells per liter | 0.5 (Standard Deviation) | 144 |
| Placebo/Cladribine Low Dose (PPLL) | -0.6 10^9 cells per liter | 0.6 (Standard Deviation) | 187 |
| Cladribine Low/Placebo (LLPP) | -7.7 10^9 cells per liter | 26.2 (Standard Deviation) | 73 |
| Cladribine High Dose/Placebo (HLPP) | -11.9 10^9 cells per liter | 35.3 (Standard Deviation) | 62 |
| Cladribine Low/Low Dose (LLLL) | -20.6 10^9 cells per liter | 37.9 (Standard Deviation) | 137 |
| Cladribine High/Low Dose (HLLL) | -9.7 10^9 cells per liter | 51.2 (Standard Deviation) | 144 |
| Placebo/Cladribine Low Dose (PPLL) | -34.0 10^9 cells per liter | 37.2 (Standard Deviation) | 187 |
| Cladribine Low/Placebo (LLPP) | 0.8 10^9 cells per liter | 1.5 (Standard Deviation) | 73 |
| Cladribine High Dose/Placebo (HLPP) | 0.5 10^9 cells per liter | 1.2 (Standard Deviation) | 62 |
| Cladribine Low/Low Dose (LLLL) | -0.2 10^9 cells per liter | 1.5 (Standard Deviation) | 137 |
| Cladribine High/Low Dose (HLLL) | -0.1 10^9 cells per liter | 1.4 (Standard Deviation) | 144 |
| Placebo/Cladribine Low Dose (PPLL) | -0.9 10^9 cells per liter | 1.7 (Standard Deviation) | 187 |
| Cladribine Low/Placebo (LLPP) | 0.4 10^9 cells per liter | 1.3 (Standard Deviation) | 73 |
| Cladribine High Dose/Placebo (HLPP) | 0.1 10^9 cells per liter | 1.2 (Standard Deviation) | 62 |
| Cladribine Low/Low Dose (LLLL) | -0.2 10^9 cells per liter | 1.4 (Standard Deviation) | 137 |
| Cladribine High/Low Dose (HLLL) | -0.2 10^9 cells per liter | 1.3 (Standard Deviation) | 144 |
| Placebo/Cladribine Low Dose (PPLL) | -0.3 10^9 cells per liter | 1.7 (Standard Deviation) | 187 |
Safety Population: Mean Change From Baseline in Hemoglobin at Week 120
Baseline, Week 120
| Group | Value | Interval | Number analysed |
|---|---|---|---|
| Cladribine Low/Placebo (LLPP) | 0.2 grams per deciliter (g/dL) | 0.9 (Standard Deviation) | 73 |
| Cladribine High Dose/Placebo (HLPP) | 0.2 grams per deciliter (g/dL) | 0.7 (Standard Deviation) | 62 |
| Cladribine Low/Low Dose (LLLL) | -0.1 grams per deciliter (g/dL) | 0.9 (Standard Deviation) | 137 |
| Cladribine High/Low Dose (HLLL) | 0.1 grams per deciliter (g/dL) | 0.9 (Standard Deviation) | 144 |
| Placebo/Cladribine Low Dose (PPLL) | -0.1 grams per deciliter (g/dL) | 0.9 (Standard Deviation) | 187 |
Safety Population: Mean Change From Baseline in Aspartate Aminotransferase and Alanine Aminotransferase at Week 120
Baseline, Week 120
| Group | Value | Interval | Number analysed |
|---|---|---|---|
| Cladribine Low/Placebo (LLPP) | 0.7 Units per litre (U/L) | 10.6 (Standard Deviation) | 72 |
| Cladribine High Dose/Placebo (HLPP) | -1.1 Units per litre (U/L) | 6.4 (Standard Deviation) | 62 |
| Cladribine Low/Low Dose (LLLL) | 2.2 Units per litre (U/L) | 7.3 (Standard Deviation) | 137 |
| Cladribine High/Low Dose (HLLL) | 0.7 Units per litre (U/L) | 11.3 (Standard Deviation) | 142 |
| Placebo/Cladribine Low Dose (PPLL) | 0.5 Units per litre (U/L) | 5.1 (Standard Deviation) | 185 |
| Cladribine Low/Placebo (LLPP) | 2.2 Units per litre (U/L) | 26 (Standard Deviation) | 72 |
| Cladribine High Dose/Placebo (HLPP) | -1.0 Units per litre (U/L) | 11.7 (Standard Deviation) | 62 |
| Cladribine Low/Low Dose (LLLL) | 4.3 Units per litre (U/L) | 14.3 (Standard Deviation) | 137 |
| Cladribine High/Low Dose (HLLL) | 0.7 Units per litre (U/L) | 17.5 (Standard Deviation) | 142 |
| Placebo/Cladribine Low Dose (PPLL) | 1.4 Units per litre (U/L) | 12.2 (Standard Deviation) | 185 |
Safety Population: Mean Change From Baseline in Bilirubin at Week 120
Baseline, Week 120
| Group | Value | Interval | Number analysed |
|---|---|---|---|
| Cladribine Low/Placebo (LLPP) | 0.1 micromoles per liter (mcmol/L) | 3.7 (Standard Deviation) | 73 |
| Cladribine High Dose/Placebo (HLPP) | 0.0 micromoles per liter (mcmol/L) | 3.5 (Standard Deviation) | 62 |
| Cladribine Low/Low Dose (LLLL) | -0.8 micromoles per liter (mcmol/L) | 3.7 (Standard Deviation) | 137 |
| Cladribine High/Low Dose (HLLL) | -0.8 micromoles per liter (mcmol/L) | 3.3 (Standard Deviation) | 144 |
| Placebo/Cladribine Low Dose (PPLL) | -0.4 micromoles per liter (mcmol/L) | 3.7 (Standard Deviation) | 186 |
Safety Population: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs
Baseline up to Week 120
| Group | Value | Interval | Number analysed |
|---|---|---|---|
| Cladribine Low/Placebo (LLPP) | 74 Participants | 98 | |
| Cladribine High Dose/Placebo (HLPP) | 71 Participants | 92 | |
| Cladribine Low/Low Dose (LLLL) | 149 Participants | 186 | |
| Cladribine High/Low Dose (HLLL) | 149 Participants | 186 | |
| Placebo/Cladribine Low Dose (PPLL) | 194 Participants | 244 | |
| Cladribine Low/Placebo (LLPP) | 16 Participants | 98 | |
| Cladribine High Dose/Placebo (HLPP) | 8 Participants | 92 | |
| Cladribine Low/Low Dose (LLLL) | 25 Participants | 186 | |
| Cladribine High/Low Dose (HLLL) | 23 Participants | 186 | |
| Placebo/Cladribine Low Dose (PPLL) | 22 Participants | 244 |
SAFUP Analysis Set: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs
Baseline up to Week 120
| Group | Value | Interval | Number analysed |
|---|---|---|---|
| Placebo/No Treatment | 16 Participants | 22 | |
| Cladribine 3.5 mg/kg/No Treatment | 13 Participants | 17 | |
| Cladribine 5.25 mg/kg/No Treatment | 18 Participants | 22 | |
| Placebo/No Treatment | 2 Participants | 22 | |
| Cladribine 3.5 mg/kg/No Treatment | 1 Participants | 17 | |
| Cladribine 5.25 mg/kg/No Treatment | 3 Participants | 22 |
Safety Population: Number of Participants Who Developed Infections (Herpes Viral Infection, Viral Infectious Disorder and Opportunistic Infection), Infection-related Adverse Events and Malignancies
Baseline up to Week 120
| Group | Value | Interval | Number analysed |
|---|---|---|---|
| Cladribine Low/Placebo (LLPP) | 6 Participants | 98 | |
| Cladribine High Dose/Placebo (HLPP) | 4 Participants | 92 | |
| Cladribine Low/Low Dose (LLLL) | 6 Participants | 186 | |
| Cladribine High/Low Dose (HLLL) | 13 Participants | 186 | |
| Placebo/Cladribine Low Dose (PPLL) | 11 Participants | 244 | |
| Cladribine Low/Placebo (LLPP) | 8 Participants | 98 | |
| Cladribine High Dose/Placebo (HLPP) | 4 Participants | 92 | |
| Cladribine Low/Low Dose (LLLL) | 9 Participants | 186 | |
| Cladribine High/Low Dose (HLLL) | 17 Participants | 186 | |
| Placebo/Cladribine Low Dose (PPLL) | 15 Participants | 244 | |
| Cladribine Low/Placebo (LLPP) | 20 Participants | 98 | |
| Cladribine High Dose/Placebo (HLPP) | 16 Participants | 92 | |
| Cladribine Low/Low Dose (LLLL) | 28 Participants | 186 | |
| Cladribine High/Low Dose (HLLL) | 41 Participants | 186 | |
| Placebo/Cladribine Low Dose (PPLL) | 39 Participants | 244 | |
| Cladribine Low/Placebo (LLPP) | 49 Participants | 98 | |
| Cladribine High Dose/Placebo (HLPP) | 45 Participants | 92 | |
| Cladribine Low/Low Dose (LLLL) | 92 Participants | 186 | |
| Cladribine High/Low Dose (HLLL) | 88 Participants | 186 | |
| Placebo/Cladribine Low Dose (PPLL) | 112 Participants | 244 | |
| Cladribine Low/Placebo (LLPP) | 2 Participants | 98 | |
| Cladribine High Dose/Placebo (HLPP) | 1 Participants | 92 | |
| Cladribine Low/Low Dose (LLLL) | 7 Participants | 186 | |
| Cladribine High/Low Dose (HLLL) | 2 Participants | 186 | |
| Placebo/Cladribine Low Dose (PPLL) | 2 Participants | 244 |
SAFUP Analysis Set: Number of Participants Who Developed Infections (Herpes Viral Infection, Viral Infectious Disorder and Opportunistic Infection), Infection-related Adverse Events and Malignancies
Baseline up to Week 120
| Group | Value | Interval | Number analysed |
|---|---|---|---|
| Placebo/No Treatment | 0 Participants | 22 | |
| Cladribine 3.5 mg/kg/No Treatment | 1 Participants | 17 | |
| Cladribine 5.25 mg/kg/No Treatment | 1 Participants | 22 | |
| Placebo/No Treatment | 0 Participants | 22 | |
| Cladribine 3.5 mg/kg/No Treatment | 1 Participants | 17 | |
| Cladribine 5.25 mg/kg/No Treatment | 2 Participants | 22 | |
| Placebo/No Treatment | 6 Participants | 22 | |
| Cladribine 3.5 mg/kg/No Treatment | 5 Participants | 17 | |
| Cladribine 5.25 mg/kg/No Treatment | 3 Participants | 22 | |
| Placebo/No Treatment | 11 Participants | 22 | |
| Cladribine 3.5 mg/kg/No Treatment | 6 Participants | 17 | |
| Cladribine 5.25 mg/kg/No Treatment | 12 Participants | 22 | |
| Placebo/No Treatment | 2 Participants | 22 | |
| Cladribine 3.5 mg/kg/No Treatment | 0 Participants | 17 | |
| Cladribine 5.25 mg/kg/No Treatment | 1 Participants | 22 |
Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity
Baseline up to Week 120
| Group | Value | Interval | Number analysed |
|---|---|---|---|
| Cladribine Low/Placebo (LLPP) | Not reached | 5 | |
| Cladribine High Dose/Placebo (HLPP) | Not reached | 6 | |
| Cladribine Low/Low Dose (LLLL) | 14 Days | 8–34 | 76 |
| Cladribine High/Low Dose (HLLL) | 8 Days | 8–12 | 99 |
| Placebo/Cladribine Low Dose (PPLL) | 362 Days | 85–378 | 61 |
| Cladribine Low/Placebo (LLPP) | Not reached | 5 | |
| Cladribine High Dose/Placebo (HLPP) | Not reached | 6 | |
| Cladribine Low/Low Dose (LLLL) | 58 Days | 34–162 | 76 |
| Cladribine High/Low Dose (HLLL) | 15 Days | 12–50 | 99 |
| Placebo/Cladribine Low Dose (PPLL) | 412 Days | 379–583 | 61 |
| Cladribine Low/Placebo (LLPP) | Not reached | 5 | |
| Cladribine High Dose/Placebo (HLPP) | Not reached | 6 | |
| Cladribine Low/Low Dose (LLLL) | 108 Days | 57–379 | 76 |
| Cladribine High/Low Dose (HLLL) | 34 Days | 15–57 | 99 |
| Placebo/Cladribine Low Dose (PPLL) | 583 Days | 61 | |
| Cladribine Low/Placebo (LLPP) | Not reached | 5 | |
| Cladribine High Dose/Placebo (HLPP) | Not reached | 6 | |
| Cladribine Low/Low Dose (LLLL) | Not reached | 76 | |
| Cladribine High/Low Dose (HLLL) | 449 Days | 99 | |
| Placebo/Cladribine Low Dose (PPLL) | Not reached | 61 | |
| Cladribine Low/Placebo (LLPP) | Not reached | 5 | |
| Cladribine High Dose/Placebo (HLPP) | Not reached | 6 | |
| Cladribine Low/Low Dose (LLLL) | Not reached | 76 | |
| Cladribine High/Low Dose (HLLL) | Not reached | 99 | |
| Placebo/Cladribine Low Dose (PPLL) | Not reached | 61 | |
| Cladribine High Dose/Placebo (HLPP) | Not reached | 6 | |
| Cladribine Low/Low Dose (LLLL) | Not reached | 76 | |
| Cladribine High/Low Dose (HLLL) | Not reached | 99 | |
| Placebo/Cladribine Low Dose (PPLL) | Not reached | 61 | |
| Cladribine High Dose/Placebo (HLPP) | Not reached | 6 | |
| Cladribine Low/Low Dose (LLLL) | Not reached | 76 | |
| Cladribine High/Low Dose (HLLL) | Not reached | 99 | |
| Placebo/Cladribine Low Dose (PPLL) | Not reached | 61 | |
| Cladribine High Dose/Placebo (HLPP) | Not reached | 6 | |
| Cladribine Low/Low Dose (LLLL) | Not reached | 76 | |
| Cladribine High/Low Dose (HLLL) | Not reached | 99 | |
| Placebo/Cladribine Low Dose (PPLL) | Not reached | 61 | |
| Cladribine High Dose/Placebo (HLPP) | Not reached | 6 | |
| Cladribine Low/Low Dose (LLLL) | Not reached | 76 | |
| Cladribine High/Low Dose (HLLL) | Not reached | 99 | |
| Placebo/Cladribine Low Dose (PPLL) | Not reached | 61 | |
| Cladribine High Dose/Placebo (HLPP) | Not reached | 6 | |
| Cladribine Low/Low Dose (LLLL) | Not reached | 76 | |
| Cladribine High/Low Dose (HLLL) | Not reached | 99 | |
| Placebo/Cladribine Low Dose (PPLL) | Not reached | 61 | |
| Cladribine High Dose/Placebo (HLPP) | Not reached | 6 | |
| Cladribine Low/Low Dose (LLLL) | Not reached | 76 | |
| Cladribine High/Low Dose (HLLL) | Not reached | 99 | |
| Placebo/Cladribine Low Dose (PPLL) | Not reached | 61 | |
| Cladribine High Dose/Placebo (HLPP) | Not reached | 6 | |
| Cladribine Low/Low Dose (LLLL) | Not reached | 76 | |
| Cladribine High/Low Dose (HLLL) | Not reached | 99 | |
| Placebo/Cladribine Low Dose (PPLL) | Not reached | 61 | |
| Cladribine High Dose/Placebo (HLPP) | Not reached | 6 | |
| Cladribine Low/Low Dose (LLLL) | Not reached | 76 | |
| Cladribine High/Low Dose (HLLL) | Not reached | 99 | |
| Placebo/Cladribine Low Dose (PPLL) | Not reached | 61 | |
| Cladribine High Dose/Placebo (HLPP) | Not reached | 6 | |
| Cladribine Low/Low Dose (LLLL) | Not reached | 76 | |
| Cladribine High/Low Dose (HLLL) | Not reached | 99 | |
| Placebo/Cladribine Low Dose (PPLL) | Not reached | 61 | |
| Cladribine High Dose/Placebo (HLPP) | Not reached | 6 | |
| Cladribine Low/Low Dose (LLLL) | Not reached | 76 | |
| Cladribine High/Low Dose (HLLL) | Not reached | 99 | |
| Placebo/Cladribine Low Dose (PPLL) | Not reached | 61 | |
| Cladribine Low/Placebo (LLPP) | Not reached | 5 | |
| Cladribine High Dose/Placebo (HLPP) | Not reached | 6 | |
| Cladribine Low/Low Dose (LLLL) | Not reached | 76 | |
| Cladribine High/Low Dose (HLLL) | Not reached | 99 | |
| Placebo/Cladribine Low Dose (PPLL) | Not reached | 61 | |
| Cladribine Low/Placebo (LLPP) | Not reached | 5 | |
| Cladribine High Dose/Placebo (HLPP) | Not reached | 6 | |
| Cladribine Low/Low Dose (LLLL) | Not reached | 76 | |
| Cladribine High/Low Dose (HLLL) | Not reached | 99 | |
| Placebo/Cladribine Low Dose (PPLL) | Not reached | 61 | |
| Cladribine Low/Placebo (LLPP) | Not reached | 5 | |
| Cladribine High Dose/Placebo (HLPP) | Not reached | 6 | |
| Cladribine Low/Low Dose (LLLL) | Not reached | 76 | |
| Cladribine High/Low Dose (HLLL) | Not reached | 99 | |
| Placebo/Cladribine Low Dose (PPLL) | Not reached | 61 | |
| Cladribine Low/Placebo (LLPP) | Not reached | 5 | |
| Cladribine High Dose/Placebo (HLPP) | Not reached | 6 | |
| Cladribine Low/Low Dose (LLLL) | Not reached | 76 | |
| Cladribine High/Low Dose (HLLL) | Not reached | 99 | |
| Placebo/Cladribine Low Dose (PPLL) | Not reached | 61 | |
| Cladribine Low/Placebo (LLPP) | Not reached | 5 | |
| Cladribine High Dose/Placebo (HLPP) | Not reached | 6 | |
| Cladribine Low/Low Dose (LLLL) | Not reached | 76 | |
| Cladribine High/Low Dose (HLLL) | Not reached | 99 | |
| Placebo/Cladribine Low Dose (PPLL) | Not reached | 61 | |
| Cladribine Low/Low Dose (LLLL) | Not reached | 76 | |
| Cladribine High/Low Dose (HLLL) | Not reached | 99 | |
| Cladribine Low/Low Dose (LLLL) | Not reached | 76 | |
| Cladribine High/Low Dose (HLLL) | Not reached | 99 | |
| Cladribine Low/Low Dose (LLLL) | Not reached | 76 | |
| Cladribine High/Low Dose (HLLL) | Not reached | 99 | |
| Cladribine Low/Low Dose (LLLL) | Not reached | 76 | |
| Cladribine High/Low Dose (HLLL) | Not reached | 99 | |
| Cladribine Low/Low Dose (LLLL) | Not reached | 76 | |
| Cladribine High/Low Dose (HLLL) | Not reached | 99 | |
| Cladribine Low/Placebo (LLPP) | Not reached | 5 | |
| Cladribine High/Low Dose (HLLL) | Not reached | 99 | |
| Placebo/Cladribine Low Dose (PPLL) | Not reached | 61 | |
| Cladribine Low/Placebo (LLPP) | Not reached | 5 | |
| Cladribine High/Low Dose (HLLL) | Not reached | 99 | |
| Placebo/Cladribine Low Dose (PPLL) | Not reached | 61 | |
| Cladribine Low/Placebo (LLPP) | Not reached | 5 | |
| Cladribine High/Low Dose (HLLL) | Not reached | 99 | |
| Placebo/Cladribine Low Dose (PPLL) | Not reached | 61 | |
| Cladribine Low/Placebo (LLPP) | Not reached | 5 | |
| Cladribine High/Low Dose (HLLL) | Not reached | 99 | |
| Placebo/Cladribine Low Dose (PPLL) | Not reached | 61 | |
| Cladribine Low/Placebo (LLPP) | Not reached | 5 | |
| Cladribine High/Low Dose (HLLL) | Not reached | 99 | |
| Placebo/Cladribine Low Dose (PPLL) | Not reached | 61 | |
| Cladribine Low/Placebo (LLPP) | Not reached | 5 | |
| Cladribine Low/Low Dose (LLLL) | Not reached | 76 | |
| Cladribine High/Low Dose (HLLL) | Not reached | 99 | |
| Placebo/Cladribine Low Dose (PPLL) | Not reached | 61 | |
| Cladribine Low/Placebo (LLPP) | Not reached | 5 | |
| Cladribine Low/Low Dose (LLLL) | Not reached | 76 | |
| Cladribine High/Low Dose (HLLL) | Not reached | 99 | |
| Placebo/Cladribine Low Dose (PPLL) | Not reached | 61 | |
| Cladribine Low/Placebo (LLPP) | Not reached | 5 | |
| Cladribine Low/Low Dose (LLLL) | Not reached | 76 | |
| Cladribine High/Low Dose (HLLL) | Not reached | 99 | |
| Placebo/Cladribine Low Dose (PPLL) | Not reached | 61 | |
| Cladribine Low/Placebo (LLPP) | Not reached | 5 | |
| Cladribine Low/Low Dose (LLLL) | Not reached | 76 | |
| Cladribine High/Low Dose (HLLL) | Not reached | 99 | |
| Placebo/Cladribine Low Dose (PPLL) | Not reached | 61 | |
| Cladribine Low/Placebo (LLPP) | Not reached | 5 | |
| Cladribine Low/Low Dose (LLLL) | Not reached | 76 | |
| Cladribine High/Low Dose (HLLL) | Not reached | 99 | |
| Placebo/Cladribine Low Dose (PPLL) | Not reached | 61 |
Safety Population: Median Time to Recovery From Grade 3 or 4 Hematological and Hepatic Toxicity
Baseline up to Week 120
| Group | Value | Interval | Number analysed |
|---|---|---|---|
| Cladribine Low/Placebo (LLPP) | 22.0 Days | 14–85 | 5 |
| Cladribine High Dose/Placebo (HLPP) | 31.5 Days | 26–51 | 4 |
| Cladribine Low/Low Dose (LLLL) | 212.0 Days | 8–1184 | 69 |
| Cladribine High/Low Dose (HLLL) | 168.0 Days | 7–799 | 89 |
| Placebo/Cladribine Low Dose (PPLL) | 111.3 Days | 5–701 | 50 |
| Cladribine High Dose/Placebo (HLPP) | 99.0 Days | 99–99 | 4 |
| Cladribine Low/Low Dose (LLLL) | 64.0 Days | 64–64 | 69 |
| Cladribine High/Low Dose (HLLL) | 57.0 Days | 57–57 | 89 |
| Placebo/Cladribine Low Dose (PPLL) | 173.5 Days | 22–325 | 50 |
| Cladribine High Dose/Placebo (HLPP) | 29.0 Days | 29–29 | 4 |
| Cladribine Low/Low Dose (LLLL) | 30.0 Days | 19–295 | 69 |
| Cladribine High/Low Dose (HLLL) | 42.5 Days | 19–715 | 89 |
| Placebo/Cladribine Low Dose (PPLL) | 79.0 Days | 28–125 | 50 |
| Cladribine Low/Placebo (LLPP) | 43.0 Days | 13–91 | 5 |
| Cladribine High Dose/Placebo (HLPP) | 57.0 Days | 29–85 | 4 |
| Cladribine Low/Low Dose (LLLL) | 23.8 Days | 8–85 | 69 |
| Cladribine High/Low Dose (HLLL) | 34.0 Days | 19–127 | 89 |
| Placebo/Cladribine Low Dose (PPLL) | 37.5 Days | 15–162 | 50 |
| Cladribine High/Low Dose (HLLL) | 197.0 Days | 197–197 | 89 |
| Cladribine Low/Placebo (LLPP) | 72.5 Days | 51–94 | 5 |
| Cladribine High/Low Dose (HLLL) | 73.0 Days | 19–127 | 89 |
| Placebo/Cladribine Low Dose (PPLL) | 15.0 Days | 1–55 | 50 |
| Cladribine Low/Placebo (LLPP) | 72.5 Days | 51–94 | 5 |
| Cladribine Low/Low Dose (LLLL) | 84.0 Days | 84–84 | 69 |
| Cladribine High/Low Dose (HLLL) | 18.0 Days | 18–18 | 89 |
| Placebo/Cladribine Low Dose (PPLL) | 55.0 Days | 55–55 | 50 |
Safety Population: Mean Time to Recovery From Grade 3 or 4 Hematological and Liver Toxicity
Baseline up to Week 120
| Group | Value | Interval | Number analysed |
|---|---|---|---|
| Cladribine Low/Placebo (LLPP) | 41.0 Days | 33.5 (Standard Deviation) | 5 |
| Cladribine High Dose/Placebo (HLPP) | 34.9 Days | 11.7 (Standard Deviation) | 4 |
| Cladribine Low/Low Dose (LLLL) | 256.7 Days | 239.7 (Standard Deviation) | 69 |
| Cladribine High/Low Dose (HLLL) | 241.8 Days | 216.1 (Standard Deviation) | 89 |
| Placebo/Cladribine Low Dose (PPLL) | 160.2 Days | 160.4 (Standard Deviation) | 50 |
| Cladribine High Dose/Placebo (HLPP) | 99.0 Days | 4 | |
| Cladribine Low/Low Dose (LLLL) | 64.0 Days | 69 | |
| Cladribine High/Low Dose (HLLL) | 57.0 Days | 89 | |
| Placebo/Cladribine Low Dose (PPLL) | 173.5 Days | 214.3 (Standard Deviation) | 50 |
| Cladribine High Dose/Placebo (HLPP) | 29.0 Days | 4 | |
| Cladribine Low/Low Dose (LLLL) | 79.3 Days | 91.9 (Standard Deviation) | 69 |
| Cladribine High/Low Dose (HLLL) | 132.0 Days | 213.9 (Standard Deviation) | 89 |
| Placebo/Cladribine Low Dose (PPLL) | 71.5 Days | 39.7 (Standard Deviation) | 50 |
| Cladribine Low/Placebo (LLPP) | 49.0 Days | 39.3 (Standard Deviation) | 5 |
| Cladribine High Dose/Placebo (HLPP) | 57.0 Days | 39.6 (Standard Deviation) | 4 |
| Cladribine Low/Low Dose (LLLL) | 35.3 Days | 29.9 (Standard Deviation) | 69 |
| Cladribine High/Low Dose (HLLL) | 46.8 Days | 35.1 (Standard Deviation) | 89 |
| Placebo/Cladribine Low Dose (PPLL) | 61.0 Days | 55.3 (Standard Deviation) | 50 |
| Cladribine High/Low Dose (HLLL) | 197.0 Days | 89 | |
| Cladribine Low/Placebo (LLPP) | 72.5 Days | 30.4 (Standard Deviation) | 5 |
| Cladribine High/Low Dose (HLLL) | 73.0 Days | 76.4 (Standard Deviation) | 89 |
| Placebo/Cladribine Low Dose (PPLL) | 23.7 Days | 28 (Standard Deviation) | 50 |
| Cladribine Low/Placebo (LLPP) | 72.5 Days | 30.4 (Standard Deviation) | 5 |
| Cladribine Low/Low Dose (LLLL) | 84.0 Days | 69 | |
| Cladribine High/Low Dose (HLLL) | 18.0 Days | 89 | |
| Placebo/Cladribine Low Dose (PPLL) | 55.0 Days | 50 |
Safety Population: Median Time to Nadir of Absolute Lymphocyte Count
Baseline up to Week 120
| Group | Value | Interval | Number analysed |
|---|---|---|---|
| Cladribine Low/Placebo (LLPP) | 162.0 Days | 86–372 | 54 |
| Cladribine High Dose/Placebo (HLPP) | 93.0 Days | 37–252 | 57 |
| Cladribine Low/Low Dose (LLLL) | 365.0 Days | 246–379 | 177 |
| Cladribine High/Low Dose (HLLL) | 162.0 Days | 106–359 | 175 |
| Placebo/Cladribine Low Dose (PPLL) | 380.0 Days | 379–400 | 227 |
Safety Population: Mean Time to Nadir of Absolute Lymphocyte Count
Baseline up to Week 120
| Group | Value | Interval | Number analysed |
|---|---|---|---|
| Cladribine Low/Placebo (LLPP) | 292.0 Days | 296.7 (Standard Deviation) | 54 |
| Cladribine High Dose/Placebo (HLPP) | 193.6 Days | 219.1 (Standard Deviation) | 57 |
| Cladribine Low/Low Dose (LLLL) | 276.7 Days | 191.7 (Standard Deviation) | 177 |
| Cladribine High/Low Dose (HLLL) | 241.1 Days | 200.3 (Standard Deviation) | 175 |
| Placebo/Cladribine Low Dose (PPLL) | 362.9 Days | 177.5 (Standard Deviation) | 227 |
Safety Population: Mean Time to Recovery From Nadir of Absolute Lymphocyte Count to Normal Value
Baseline up to Week 120
| Group | Value | Interval | Number analysed |
|---|---|---|---|
| Cladribine Low/Placebo (LLPP) | 79.0 Days | 72.4 (Standard Deviation) | 47 |
| Cladribine High Dose/Placebo (HLPP) | 72.7 Days | 61.3 (Standard Deviation) | 52 |
| Cladribine Low/Low Dose (LLLL) | 237.5 Days | 214.7 (Standard Deviation) | 130 |
| Cladribine High/Low Dose (HLLL) | 245.3 Days | 222.3 (Standard Deviation) | 128 |
| Placebo/Cladribine Low Dose (PPLL) | 187.8 Days | 180.9 (Standard Deviation) | 185 |
Safety Population: Mean Change in Corrected QT (QTc) Interval From Baseline
Baseline, Week 5, 48, 52 and 96
| Group | Value | Interval | Number analysed |
|---|---|---|---|
| Cladribine Low/Placebo (LLPP) | 7.0 milliseconds | 21.6 (Standard Deviation) | 25 |
| Cladribine High Dose/Placebo (HLPP) | 7.4 milliseconds | 21.2 (Standard Deviation) | 18 |
| Cladribine Low/Low Dose (LLLL) | 4.5 milliseconds | 20.6 (Standard Deviation) | 31 |
| Cladribine High/Low Dose (HLLL) | 4.3 milliseconds | 16.2 (Standard Deviation) | 35 |
| Placebo/Cladribine Low Dose (PPLL) | 0.7 milliseconds | 18.8 (Standard Deviation) | 41 |
| Cladribine Low/Placebo (LLPP) | 16.9 milliseconds | 18.6 (Standard Deviation) | 25 |
| Cladribine High Dose/Placebo (HLPP) | 7.4 milliseconds | 23.6 (Standard Deviation) | 18 |
| Cladribine Low/Low Dose (LLLL) | 9.3 milliseconds | 19.8 (Standard Deviation) | 31 |
| Cladribine High/Low Dose (HLLL) | 11.3 milliseconds | 19.5 (Standard Deviation) | 35 |
| Placebo/Cladribine Low Dose (PPLL) | 7.2 milliseconds | 19.6 (Standard Deviation) | 41 |
| Cladribine Low/Placebo (LLPP) | 14.9 milliseconds | 17.5 (Standard Deviation) | 25 |
| Cladribine High Dose/Placebo (HLPP) | 22.3 milliseconds | 25.4 (Standard Deviation) | 18 |
| Cladribine Low/Low Dose (LLLL) | 8.4 milliseconds | 22.8 (Standard Deviation) | 31 |
| Cladribine High/Low Dose (HLLL) | 5.2 milliseconds | 18.8 (Standard Deviation) | 35 |
| Placebo/Cladribine Low Dose (PPLL) | -1.2 milliseconds | 16.6 (Standard Deviation) | 41 |
| Cladribine Low/Placebo (LLPP) | 5.8 milliseconds | 25.5 (Standard Deviation) | 25 |
| Cladribine High Dose/Placebo (HLPP) | -4.5 milliseconds | 32.5 (Standard Deviation) | 18 |
| Cladribine Low/Low Dose (LLLL) | -12.5 milliseconds | 22.2 (Standard Deviation) | 31 |
| Cladribine High/Low Dose (HLLL) | 1.6 milliseconds | 22.7 (Standard Deviation) | 35 |
| Placebo/Cladribine Low Dose (PPLL) | -6.2 milliseconds | 19.2 (Standard Deviation) | 41 |
Values as posted on ClinicalTrials.gov. Outcomes measured differently across trials are not directly comparable.
Safety
| Group | Participants at risk | Serious adverse events | Deaths |
|---|---|---|---|
| Cladribine Low/Placebo (LLPP) | 98 | 16 (16.3%) | 2 |
| Cladribine High Dose/Placebo (HLPP) | 92 | 8 (8.7%) | 0 |
| Cladribine Low/Low Dose (LLLL) | 186 | 25 (13.4%) | 1 |
| Cladribine High/Low Dose (HLLL) | 186 | 23 (12.4%) | 0 |
| Placebo/Cladribine Low Dose (PPLL) | 244 | 22 (9.0%) | 0 |
| Placebo/No Treatment | 22 | 2 (9.1%) | 0 |
| Cladribine 3.5 mg/kg/No Treatment | 17 | 1 (5.9%) | 0 |
| Cladribine 5.25 mg/kg/No Treatment | 22 | 3 (13.6%) | 0 |
As posted on ClinicalTrials.gov. Serious adverse events include any serious health event during the trial, whether or not the treatment caused it.
What it measured
Main measures
Safety Population: Percentage of Participants With at Least 1 Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE) Grade 4 Hematologic and Hepatic Toxicity
Baseline up to Week 120
Immune responseSafetySafety Population: Mean Change From Baseline in Absolute Lymphocyte Count, Platelet, Neutrophils and Leukocytes at Week 120
Baseline, Week 120
Immune responseSafetySafety Population: Mean Change From Baseline in Hemoglobin at Week 120
Baseline, Week 120
SafetySafety Population: Mean Change From Baseline in Aspartate Aminotransferase and Alanine Aminotransferase at Week 120
Baseline, Week 120
SafetySafety Population: Mean Change From Baseline in Bilirubin at Week 120
Baseline, Week 120
SafetySafety Population: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs
Baseline up to Week 120
SafetySAFUP Analysis Set: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs
Baseline up to Week 120
SafetySafety Population: Number of Participants Who Developed Infections (Herpes Viral Infection, Viral Infectious Disorder and Opportunistic Infection), Infection-related Adverse Events and Malignancies
Baseline up to Week 120
SafetySAFUP Analysis Set: Number of Participants Who Developed Infections (Herpes Viral Infection, Viral Infectious Disorder and Opportunistic Infection), Infection-related Adverse Events and Malignancies
Baseline up to Week 120
SafetySafety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity
Baseline up to Week 120
Immune responseSafetySafety Population: Median Time to Recovery From Grade 3 or 4 Hematological and Hepatic Toxicity
Baseline up to Week 120
Immune responseSafetySafety Population: Mean Time to Recovery From Grade 3 or 4 Hematological and Liver Toxicity
Baseline up to Week 120
Immune responseSafetySafety Population: Median Time to Nadir of Absolute Lymphocyte Count
Baseline up to Week 120
Immune responseSafetySafety Population: Mean Time to Nadir of Absolute Lymphocyte Count
Baseline up to Week 120
Immune responseSafetySafety Population: Mean Time to Recovery From Nadir of Absolute Lymphocyte Count to Normal Value
Baseline up to Week 120
Immune responseSafetySafety Population: Mean Change in Corrected QT (QTc) Interval From Baseline
Baseline, Week 5, 48, 52 and 96
SafetySafety endpoints:
Safety
Other measures (1)
Not Applicable
Who could take part
Relapsing MS · 18 to 65
Show the full criteria
Inclusion criteria
* Randomized in Trial 25643 and satisfied one of the following: * Completed randomized treatment course and scheduled visits for the full 96 weeks; or * Did not complete the randomized treatment course in Trial 25643 but elected to receive rescue treatment with Rebif®, another beta-interferon, or glatiramer acetate and completed scheduled clinic visits for the full 96 weeks; or * Did not complete the randomized treatment course in Trial 25643, declined rescue with Rebif®, another beta-interferon, or glatiramer acetate and still completed scheduled clinic visits for the full 96 weeks; or * Did not complete the randomized treatment course in Trial 25643, were not eligible for rescue option with Rebif®, and still completed scheduled clinic visits for the full 96 weeks * Male or female, between 18 and 65 years of age (inclusive, at time of informed consent for Trial 25643) * No medical history or evidence of latent tuberculosis infection (LTBI) or tuberculosis (TB), as evidenced by TB skin test or chest X-ray * All of the following laboratory hematologic parameters evaluated as normal (as define below, inclusively) within 28 days of first dosing of blinded study medication at study Day 1: * Hemoglobin = 11.6 to 16.2 gram per deciliter (g/dL) * Leukocytes (total white blood cell) = 4.1 to 12.3*10\^3 per microliter * Absolute lymphocyte count (ALC) = 1.02 to 3.36*10\^3 per microliter * Absolute neutrophil count (ANC) = 2.03 to 8.36*10\^3 per microliter * Platelet count = 140 to 450*10\^3 per microliter * Other protocol-defined inclusion/exclusion criteria may apply
Exclusion criteria
* Participants who were not enrolled in Trial 25643 * Participant has moderate to severe renal impairment * Use of mitoxantrone, total lymphoid irradiation, myelosuppressive therapy, campath-1h, cyclophosphamide, azathioprine, methotrexate or natalizumab at any time during and since Trial 25643 * Use of cytokine or anti-cytokine therapy, intravenous immunoglobulin (IVIG) or plasmapheresis at any time during and since Trial 25643 * Treatment with oral or systemic corticosteroids or adrenocorticotropic hormone within 28 days before Study Day 1
As registered. Criteria can change, so ask the trial team or your neurologist.
About this trial
In the sponsor's words
The purpose of this extension trial was to further evaluate the safety and tolerability of oral cladribine in subjects who have previously completed treatment within Trial 25643 (CLARITY). This trial also explored clinical benefit of prolonged 192-week versus 96-week treatment.
Papers
Results
Long-Term Disease Stability Assessed by the Expanded Disability Status Scale in Patients Treated with Cladribine Tablets 3.5 mg/kg for Relapsing Multiple Sclerosis: An Exploratory Post Hoc Analysis of the CLARITY and CLARITY Extension Studies.Adv Ther · 2021
Results
Stefano N, Sormani MP, Giovannoni G, Rammohan K, Leist TP, Coyle PK, Dangond F, Alexandri N, Galazka A. Relapses in people with multiple sclerosis treated with cladribine tablets followed for up to 5 years: a plain language summary. Neurodegener Dis Manag. 2022 Dec;12(6):303-310. doi: 10.2217/nmt-2022-0019. Epub 2022 Aug 26.Results
Giovannoni G, Comi G, Rammohan K, Rieckmann P, Dangond F, Jack D, Vermersch P. Disease stability over five years in people with multiple sclerosis treated with cladribine tablets: a plain language summary. Neurodegener Dis Manag. 2022 Dec;12(6):295-301. doi: 10.2217/nmt-2022-0018. Epub 2022 Aug 26.Results
Giovannoni G, Coyle PK, Vermersch P, Walker B, Aldridge J, Nolting A, Galazka A, Lemieux C, Leist TP. Integrated Lymphopenia Analysis in Younger and Older Patients With Multiple Sclerosis Treated With Cladribine Tablets. Front Immunol. 2021 Dec 24;12:763433. doi: 10.3389/fimmu.2021.763433. eCollection 2021.Results
De Stefano N, Sormani MP, Giovannoni G, Rammohan K, Leist T, Coyle PK, Dangond F, Keller B, Alexandri N, Galazka A. Analysis of frequency and severity of relapses in multiple sclerosis patients treated with cladribine tablets or placebo: The CLARITY and CLARITY Extension studies. Mult Scler. 2022 Jan;28(1):111-120. doi: 10.1177/13524585211010294. Epub 2021 May 10.Results
Giovannoni G, Galazka A, Schick R, Leist T, Comi G, Montalban X, Damian D, Dangond F, Cook S. Pregnancy Outcomes During the Clinical Development Program of Cladribine in Multiple Sclerosis: An Integrated Analysis of Safety. Drug Saf. 2020 Jul;43(7):635-643. doi: 10.1007/s40264-020-00948-x.Results
Comi G, Cook S, Rammohan K, Soelberg Sorensen P, Vermersch P, Adeniji AK, Dangond F, Giovannoni G. Long-term effects of cladribine tablets on MRI activity outcomes in patients with relapsing-remitting multiple sclerosis: the CLARITY Extension study. Ther Adv Neurol Disord. 2018 Jan 23;11:1756285617753365. doi: 10.1177/1756285617753365. eCollection 2018.
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History
Started
Feb 2008
Main results due
Dec 2011
Finished
Dec 2011
Results posted
Dec 2013
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