Clinical trial NCT02583594: A Study to Characterize Subcutaneous or Intravenous Alemtuzumab in Patients With Progressive Multiple Sclerosis
Official title: A Phase 1, Exploratory, Randomized, Open-label, 2-Arm Study to Characterize the Pharmacodynamics, Pharmacokinetics, Safety, and Tolerability of Alemtuzumab 12mg Administered Subcutaneously or Intravenously in Patients With Progressive Multiple Sclerosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Progressive Multiple Sclerosis
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2015-10-22
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Primary Objective:

* To characterize the pharmacodynamic profile of 2 treatment courses of alemtuzumab administered by subcutaneous injection and 2 treatment courses of alemtuzumab administered by intravenous infusion in patients with progressive multiple sclerosis.

Secondary Objectives:

* To characterize the pharmacokinetic profiles of alemtuzumab administered by subcutaneous injection or intravenous infusion to patients with progressive multiple sclerosis.
* To characterize the safety and tolerability of alemtuzumab administered by subcutaneous injection or intravenous infusion to patients with progressive multiple sclerosis.

Detailed description: The duration of study per patient will be approximately 61 months.

Eligibility criteria: Inclusion criteria:

* Male or female adults with a diagnosis of Multiple Sclerosis (MS) based on 2010 revision of McDonald criteria.
* Diagnosis of progressive MS including primary progressive MS and secondary progressive MS.
* Age ≥18 years.
* Signed informed consent form.
* Covered by a health insurance system where applicable, and/or in compliance with the recommendations of the national laws in force relating to biomedical research.
* Not under any administrative or legal supervision.

Exclusion criteria:

* Patients with relapsing remitting MS.
* Any prior treatment with alemtuzumab or other anti-CD52 antibodies.
* Treatment with natalizumab in the 4 months prior to Study Visit 1.
* Progressive multifocal leukoencephalopathy (PML), or any clinical or imaging signs possibly indicative of undiagnosed PML. Particular vigilance is needed for patients with prior natalizumab exposure, even if the last exposure was more than 4 months prior to Study Visit 1.
* Treatment with methotrexate, azathioprine, or cyclosporine in the past 6 months.
* Treatment with mitoxantrone, cyclophosphamide, cladribine, rituximab, or any other immunosuppressant or cytotoxic therapy (other than steroids) in the last 12 months, or determined by the treating physician to have residual immune suppression from these treatments.
* Treatment with glatiramer acetate or interferon beta in the past 4 weeks.
* Treatment with fingolimod within the past 2 months.
* Treatment with dimethyl fumarate in the past 4 weeks.
* Treatment with teriflunomide within the past 12 months unless the patient has completed an accelerated clearance with cholestyramine or activated charcoal.
* Any known contraindications to the symptomatic therapy used in the infusion management guidance for this study.
* Hypersensitivity or contraindication to acyclovir.
* History of a hypersensitivity reaction other than localized injection site reaction to any biological molecule.
* If female, pregnancy (defined as positive β-HCG blood test) or lactating or breast-feeding.
* Current participation in another investigational interventional study.
* Any significant change in chronic treatment medication (ie, new chronic medication) within 14 days before inclusion.
* An investigational medicinal product within 3 months or 5 half-lives, whichever is longer, before study inclusion.
* Total lymphocyte or CD3+ counts are below normal limits at screening. If abnormal cell count(s) return to within normal limits, eligibility may be reassessed.
* Live, attenuated vaccine within 3 months prior to the randomization (Day 1) visit, such as varicella-zoster, oral polio, rubella vaccines.
* Any clinically relevant findings in the physical examination, medical history, or laboratory assessments which would compromise the safety of the patient.
* Women of childbearing potential not protected by highly-effective method(s) of birth control and/or who are unwilling or unable to be tested for pregnancy.
* Latent or active tuberculosis infection, verified by testing as per local practice.
* Infection with human immunodeficiency virus (HIV).
* Known Hepatitis B (HBV) or Hepatitis C (HCV) infection.
* Active infection, eg, deep tissue infection, that the Investigator considers sufficiently serious to preclude study participation.
* Prior history of invasive fungal infections.
* Any patient who, in the judgment of the Investigator, is likely to be noncompliant during the study, or unable to cooperate because of a language problem or poor mental development.
* Any patient in the exclusion period of a previous study according to applicable regulations.
* Any patient who cannot be contacted in case of emergency.
* Any patient who is the Investigator or any subinvestigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the protocol.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Primary outcomes:
measure: Change from baseline in the CD3+ lymphocyte subset after alemtuzumab administration
timeFrame: Baseline, 30 days after each treatment course
Secondary outcomes:
measure: Change from baseline in lymphocyte subsets after alemtuzumab administration
timeFrame: Baseline, 30 days after each treatment course
measure: Change from baseline in total lymphocyte count after alemtuzumab administration
timeFrame: Baseline, 30 days after each treatment course
measure: Change from baseline in helper/suppressor ratio after alemtuzumab administration
timeFrame: Baseline, 30 days after each treatment course
measure: Assessment of pharmacokinetic parameter after alemtuzumab administration: maximum plasma concentration observed (Cmax)
timeFrame: 30 days after each treatment course
measure: Assessment of pharmacokinetic parameter after alemtuzumab administration: time to reach Cmax (Tmax)
timeFrame: 30 days after each treatment course
measure: Assessment of pharmacokinetic parameter after alemtuzumab administration: area under plasma concentration versus time curve from time zero until the last measurable concentration (AUClast)
timeFrame: 30 days after each treatment course
measure: Assessment of pharmacokinetic parameter after alemtuzumab administration: area under plasma concentration (AUC)
timeFrame: 30 days after each treatment course
measure: Assessment of pharmacokinetic parameter after alemtuzumab administration: terminal half-life (t1/2z)
timeFrame: 30 days after each treatment course
measure: Number of patients with adverse events
timeFrame: 4 years
measure: Number of patients with adverse events of special interest
timeFrame: 4 years
measure: Number of patients with injection site reactions
timeFrame: 2 years
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: Investigational Site Number 724001
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: