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Keratinocyte Growth Factor to Prevent Autoimmunity After Alemtuzumab Treatment of Multiple Sclerosis

Information source: Cambridge University Hospitals NHS Foundation Trust
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Multiple Sclerosis

Intervention: Palifermin (Drug); Alemtuzumab (Drug)

Phase: Phase 1/Phase 2

Status: Recruiting

Sponsored by: Cambridge University Hospitals NHS Foundation Trust

Official(s) and/or principal investigator(s):
Alasdair Coles, Phd FRCP, Principal Investigator, Affiliation: University of Cambridge

Overall contact:
Alasdair Coles, PhD FRCP, Phone: 441223216751, Email: ajc1020@medschl.cam.ac.uk

Summary

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®).

Clinical Details

Official title: Keratinocyte Growth Factor - Promoting Thymic Reconstitution and Preventing Autoimmunity After Alemtuzumab (Campath-1H) Treatment of Multiple Sclerosis

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Primary outcome: incidence of clinical autoimmunity

Secondary outcome:

Absolute numbers of naive T cells

Safety events

Detailed description: This is a single-centre, double-blinded, randomised controlled trial of palifermin (Kepivance) vs. placebo in the prevention of autoimmunity following alemtuzumab treatment of multiple sclerosis. The dose of palifermin (kepivance)used in this trial will be informed by a dose-escalation study.

Eligibility

Minimum age: 18 Months. Maximum age: 50 Years. Gender(s): Both.

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.

Locations and Contacts

Alasdair Coles, PhD FRCP, Phone: 441223216751, Email: ajc1020@medschl.cam.ac.uk

Addenbrooke's Hospital, Cambridge, Cambridgeshire CB2 2QQ, United Kingdom; Recruiting
Karen May, Phone: 441223216751, Email: km480@medschl.cam.ac.uk
Alasdair Coles, PhD FRCP, Principal Investigator
Additional Information

Information for patients on protocol

Related publications:

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 β-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.

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.

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.

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.

Bruinsma M, van Soest PL, Leenen PJ, Lambrecht BN, Cupedo T, Löwenberg 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.

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.

Min D, Panoskaltsis-Mortari A, Kuro-O M, Holländer 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. Epub 2006 Nov 30.

Starting date: June 2012
Last updated: October 23, 2012

Page last updated: August 23, 2015

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