CAM-THY: Keratinocyte Growth Factor to Prevent Autoimmunity After Alemtuzumab Treatment of Multiple Sclerosis

Sponsor

Cambridge University Hospitals NHS Foundation Trust (Other)

Overall Status

Terminated

CT.gov ID

NCT01712945

Collaborator

(none)

Enrollment

Location

Arms

Actual Duration (Months)

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief 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®).

Condition or Disease	Intervention/Treatment	Phase
Multiple Sclerosis	Drug: Palifermin Drug: Alemtuzumab	Phase 1/Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

40 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

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

Actual Study Start Date :

Jun 1, 2012

Actual Primary Completion Date :

Aug 1, 2017

Actual Study Completion Date :

Oct 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Palifermin (and Alemtuzumab) Palifermin (Kepivance®), at the maximum identified tolerated dose will be administered by intravenous bolus on days -5, -4. -3 prior to, and on days 8, 9 and 10 after each cycle of alemtuzumab, then again on 3 consecutive days at month 1 and month 3 after each cycle of alemtuzumab. Patients will be observed for adverse reactions for at least 1 to 2 hours following each bolus dose. Initial treatment alemtuzumab will be administered as a fixed total dose of 60 mg IV over 5 consecutive days (12mg/day). For re-treatment at Month 12, alemtuzumab will be administered as a fixed total dose of 36mg IV over 3 consecutive days (12mg/day).	Drug: Palifermin Palifermin (Kepivance®) administered by intravenous bolus on days -5, -4. -3 prior to, and on days 8, 9 and 10 after each cycle of alemtuzumab, then again on 3 consecutive days at month 1 and month 3 after each cycle of alemtuzumab. Patients will be observed for adverse reactions for at least 1 to 2 hours following each bolus dose. Other Names: Kepivance keratinocyte growth factor Drug: Alemtuzumab Initial treatment alemtuzumab will be administered as a fixed total dose of 60 mg IV over 5 consecutive days (12mg/day). For re-treatment at Month 12, alemtuzumab will be administered as a fixed total dose of 36mg IV over 3 consecutive days (12mg/day). Other Names: Campath-1H
Placebo Comparator: Placebo (and Alemtuzumab) Initial treatment alemtuzumab will be administered as a fixed total dose of 60 mg IV over 5 consecutive days (12mg/day). For re-treatment at Month 12, alemtuzumab will be administered as a fixed total dose of 36mg IV over 3 consecutive days (12mg/day).	Drug: Alemtuzumab Initial treatment alemtuzumab will be administered as a fixed total dose of 60 mg IV over 5 consecutive days (12mg/day). For re-treatment at Month 12, alemtuzumab will be administered as a fixed total dose of 36mg IV over 3 consecutive days (12mg/day). Other Names: Campath-1H

Arm

Intervention/Treatment

Experimental: Palifermin (and Alemtuzumab)

Palifermin (Kepivance®), at the maximum identified tolerated dose will be administered by intravenous bolus on days -5, -4. -3 prior to, and on days 8, 9 and 10 after each cycle of alemtuzumab, then again on 3 consecutive days at month 1 and month 3 after each cycle of alemtuzumab. Patients will be observed for adverse reactions for at least 1 to 2 hours following each bolus dose. Initial treatment alemtuzumab will be administered as a fixed total dose of 60 mg IV over 5 consecutive days (12mg/day). For re-treatment at Month 12, alemtuzumab will be administered as a fixed total dose of 36mg IV over 3 consecutive days (12mg/day).

Drug: Palifermin

Palifermin (Kepivance®) administered by intravenous bolus on days -5, -4. -3 prior to, and on days 8, 9 and 10 after each cycle of alemtuzumab, then again on 3 consecutive days at month 1 and month 3 after each cycle of alemtuzumab. Patients will be observed for adverse reactions for at least 1 to 2 hours following each bolus dose.

Other Names:

Kepivance

keratinocyte growth factor

Drug: Alemtuzumab

Initial treatment alemtuzumab will be administered as a fixed total dose of 60 mg IV over 5 consecutive days (12mg/day). For re-treatment at Month 12, alemtuzumab will be administered as a fixed total dose of 36mg IV over 3 consecutive days (12mg/day).

Other Names:

Campath-1H

Placebo Comparator: Placebo (and Alemtuzumab)

Drug: Alemtuzumab

Other Names:

Campath-1H

Outcome Measures

Primary Outcome 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

Secondary Outcome Measures

Absolute numbers of naive T cells [within 30 months of starting treatment with alemtuzumab]
Absolute numbers of naive T cells
Safety events [within 30 months of starting treatment with alemtuzumab]
Safety outcomes - incidence and nature of adverse events

Other Outcome Measures

Time at which autoimmunity develops [Within 30 months after alemtuzumab]
Reconstitution of lymphocyte subsets [within 30 months of starting treatment with alemtuzumab]
Percentage of naive, central memory, effector memory and effector memory RA cells within the CD4 and CD8 T cell populations
T cell receptor (TCR) clonality [within 30 months of starting treatment with alemtuzumab]
T cell receptor (TCR) clonality
Thymic function [within 30 months of starting treatment with alemtuzumab]
Thymic function - determined by measuring TRECs
Thymic volume [within 30 months of starting treatment with alemtuzumab]
Thymic volume and density - as assessed by non-contrast enhanced, low dose CT scans of the chest performed at baseline and month 6.
Thymic density [within 30 months of starting treatment with alemtuzumab]
Thymic volume and density - as assessed by non-contrast enhanced, low dose CT scans of the chest performed at baseline and month 6.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Months to 50 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.