Keratinocyte Growth Factor to Prevent Autoimmunity After Alemtuzumab T
Keratinocyte Growth Factor - Promoting Thymic Reconstitution and Preventing Autoimmunity After Alemtuzumab (Campath-1H) Treatment of Multiple Sclerosis
What it found
The trial ended early for another reason (see below).
Reason given: interim anlaysis failed: palifermin does not promote thymopoeisis after alemtuzumab
What was tested
Treatment tested
- Palifermin
Fibroblast growth factor receptor 2 agonist
Given to everyone in the trial
- Alemtuzumab
CAMPATH-1 antigen inhibitor
What it measured
Main measures
incidence of clinical autoimmunity
within 30 months of starting treatment with alemtuzumab
The primary endpoint is incidence of clinical autoimmunity within 30 months of starting treatment with alemtuzumab.
Other measures (3)
Absolute numbers of naive T cells
within 30 months of starting treatment with alemtuzumab
Safety events
within 30 months of starting treatment with alemtuzumab
Safety• Percentage of naive T cells • Safety outcomes - incidence and nature of adverse events • Percentage of central memory T cells, effector memory T cells and T effector memory RA cells - as determined by flow cytometry • Frequency of recent thymic emigrants (defined by co-expression of CD45RA and CD31 in CD4+ T cells, and by CD45RA and CD103 in CD8+ T cells) - as determined by flow cytometry •
Thinking and memoryImmune responseSafety
Who could take part
MS (type not specified) · 1.5 to 50 · EDSS 0.0 to 5.0
Show the full criteria
Inclusion criteria
* Male or non-pregnant, non-lactating female patients * > 18 years of age, and \<50 years of age inclusive * Diagnosis of MS using McDonald's 2010 criteria, including MRI abnormalities consistent with McDonald's 2010 criteria. * Onset of first MS symptoms within 10 years on the date the ICF is signed * EDSS score 0.0 to 5.0 (inclusive) at screening * At least 2 clinical episodes of MS in the 2 years prior to study entry, with at least 1 attack within 12 months, which may have occurred whilst on disease-modifying therapy, namely any beta interferon or glatiramer acetate. * Serum IL-7≤7pg/mL
Exclusion criteria
* Any progressive form of multiple sclerosis * Previous thymectomy * Previous treatment with alemtuzumab, natalizumab, mitoxantrone, cyclophosphomide, cladribine, rituximab or any other immunosuppressant or cytotoxic therapy (other than steroids and disease-modifying therapies listed above) * History of malignancy * Personal history of clinically significant autoimmune disease, other than multiple sclerosis (including but not limited to: thyroid disease, immune cytopenias, inflammatory bowel disease, diabetes, lupus, severe asthma) * Intolerance of pulsed corticosteroids, especially a history of steroid psychosis * Major systemic disease or other illness that would, in the opinion of the investigator, compromise patient safety or interfere with the interpretation of study results. * Seropositivity for human immunodeficiency virus (HIV) * Past or present hepatitis B infection (positive hepatitis B serology) * Pregnant women or male and female patients who do not agree to use effective contraception during the study. * Medical, psychiatric, cognitive or other conditions that, in the investigator's opinion, compromise the patient's ability to understand the patient information, to give informed consent, to comply with the trial protocol, or to complete the study.
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 study is to test a novel strategy to prevent the clinical problem of secondary autoimmunity following alemtuzumab treatment of multiple sclerosis. The hypothesis is that autoimmunity after alemtuzumab can be prevented by giving a drug that promotes thymic T cell regeneration (Palifermin, Kepivance®).
Papers
Results
Keratinocyte growth factor impairs human thymic recovery from lymphopenia.JCI Insight · 2019
Background
Coles AJ, Fox E, Vladic A, Gazda SK, Brinar V, Selmaj KW, Bass AD, Wynn DR, Margolin DH, Lake SL, Moran S, Palmer J, Smith MS, Compston DA. Alemtuzumab versus interferon beta-1a in early relapsing-remitting multiple sclerosis: post-hoc and subset analyses of clinical efficacy outcomes. Lancet Neurol. 2011 Apr;10(4):338-48. doi: 10.1016/S1474-4422(11)70020-5.Background
Jones JL, Phuah CL, Cox AL, Thompson SA, Ban M, Shawcross J, Walton A, Sawcer SJ, Compston A, Coles AJ. IL-21 drives secondary autoimmunity in patients with multiple sclerosis, following therapeutic lymphocyte depletion with alemtuzumab (Campath-1H). J Clin Invest. 2009 Jul;119(7):2052-61. doi: 10.1172/JCI37878. Epub 2009 Jun 22.Background
Cox AL, Thompson SA, Jones JL, Robertson VH, Hale G, Waldmann H, Compston DA, Coles AJ. Lymphocyte homeostasis following therapeutic lymphocyte depletion in multiple sclerosis. Eur J Immunol. 2005 Nov;35(11):3332-42. doi: 10.1002/eji.200535075.Background
CAMMS223 Trial Investigators; Coles AJ, Compston DA, Selmaj KW, Lake SL, Moran S, Margolin DH, Norris K, Tandon PK. Alemtuzumab vs. interferon beta-1a in early multiple sclerosis. N Engl J Med. 2008 Oct 23;359(17):1786-801. doi: 10.1056/NEJMoa0802670.Background
Bruinsma M, van Soest PL, Leenen PJ, Lambrecht BN, Cupedo T, Lowenberg B, Cornelissen JJ, Braakman E. Keratinocyte growth factor induces expansion of murine peripheral CD4+Foxp3+ regulatory T cells and increases their thymic output. J Immunol. 2007 Dec 1;179(11):7424-30. doi: 10.4049/jimmunol.179.11.7424.Background
Miller RD, Caulfield MJ, Calkins CE. Expression and regulation of a recurrent anti-erythrocyte autoantibody idiotype in spleen cells from neonatal and adult BALB/c mice. J Immunol. 1992 Apr 15;148(8):2452-5.Background
Min D, Panoskaltsis-Mortari A, Kuro-O M, Hollander GA, Blazar BR, Weinberg KI. Sustained thymopoiesis and improvement in functional immunity induced by exogenous KGF administration in murine models of aging. Blood. 2007 Mar 15;109(6):2529-37. doi: 10.1182/blood-2006-08-043794. Epub 2006 Nov 30.
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History
Started
Jun 2012
Main results due
Aug 2017
Finished
Oct 2017