A Study to Characterize Subcutaneous or Intravenous Alemtuzumab in Patients With Progressive Multiple Sclerosis

NCT02583594 | Completed Phase 1

• 3 other identifiers: TDU142602015-002550-12U1111-1171-7939
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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.

Conditions

Progressive Multiple Sclerosis

Outcome Measures

Primary Outcomes (1)

• Change from baseline in the CD3+ lymphocyte subset after alemtuzumab administration

  Baseline, 30 days after each treatment course

Secondary Outcomes (11)

• Change from baseline in lymphocyte subsets after alemtuzumab administration

  Baseline, 30 days after each treatment course

• Change from baseline in total lymphocyte count after alemtuzumab administration

  Baseline, 30 days after each treatment course

• Change from baseline in helper/suppressor ratio after alemtuzumab administration

  Baseline, 30 days after each treatment course

• Assessment of pharmacokinetic parameter after alemtuzumab administration: maximum plasma concentration observed (Cmax)

  30 days after each treatment course

• Assessment of pharmacokinetic parameter after alemtuzumab administration: time to reach Cmax (Tmax)

  30 days after each treatment course

Study Arms (2)

alemtuzumab (subcutaneous injection)

EXPERIMENTAL

Dose 1 (initial course) of alemtuzumab will be administered subcutaneously on 5 consecutive days, followed by Dose 2 (second course) on 3 consecutive days administered 12 months after initial course. Pre-medications (methylprednisolone, antihistamine \[loratadine, cetirizine, dexchlorpheniramine\], paracetamol, acyclovir) will be administered prior alemtuzumab administration.

Drug: Acyclovir; Drug: Methylprednisolone; Drug: alemtuzumab GZ402673; Drug: Paracetamol; Drug: Loratadine; Drug: Ceterizine; Drug: Dexchlorpheniramine

alemtuzumab (intravenous infusion)

EXPERIMENTAL

Dose 1 (initial course) of alemtuzumab will be administered intravenously on 5 consecutive days, followed by Dose 2 (second course) on 3 consecutive days administered 12 months after initial course. Pre-medications (methylprednisolone, antihistamine \[loratadine, cetirizine, dexchlorpheniramine\], paracetamol, acyclovir) will be administered prior alemtuzumab administration.

Drug: Acyclovir; Drug: Methylprednisolone; Drug: alemtuzumab GZ402673; Drug: Paracetamol; Drug: Loratadine; Drug: Ceterizine; Drug: Dexchlorpheniramine

Interventions

Acyclovir DRUG

Pharmaceutical form:tablet Route of administration: oral

alemtuzumab (intravenous infusion); alemtuzumab (subcutaneous injection)

Methylprednisolone DRUG

Pharmaceutical form:tablet Route of administration: oral

alemtuzumab (intravenous infusion); alemtuzumab (subcutaneous injection)

alemtuzumab GZ402673 DRUG

Pharmaceutical form:solution for infusion Route of administration: intravenous

alemtuzumab (intravenous infusion)

Paracetamol DRUG

Pharmaceutical form:tablet Route of administration: oral

alemtuzumab (intravenous infusion); alemtuzumab (subcutaneous injection)

Loratadine DRUG

Pharmaceutical form:tablet Route of administration: oral

alemtuzumab (intravenous infusion); alemtuzumab (subcutaneous injection)

Ceterizine DRUG

Pharmaceutical form:tablet Route of administration: oral

alemtuzumab (intravenous infusion); alemtuzumab (subcutaneous injection)

Dexchlorpheniramine DRUG

Pharmaceutical form:tablet Route of administration: oral

alemtuzumab (intravenous infusion); alemtuzumab (subcutaneous injection)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Genzyme, a Sanofi Company: lead

Study Sites (1)

Investigational Site Number 724001

Barcelona, 08035, Spain

Location

Related Publications (1)

• Montalban X, Rodriguez-Acevedo B, Nos C, Resina M, Forner M, Wu Y, Chirieac M. SCALA: a randomized phase I trial comparing subcutaneous and intravenous alemtuzumab in patients with progressive multiple sclerosis. Ther Adv Neurol Disord. 2024 Nov 6;17:17562864241291655. doi: 10.1177/17562864241291655. eCollection 2024.

  PMID: 39513023 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis, Chronic Progressive

Interventions

Acyclovir; Methylprednisolone; Acetaminophen; Loratadine; ceterizine hydrochloride; dexchlorpheniramine

Condition Hierarchy (Ancestors)

Multiple Sclerosis; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Cyproheptadine; Dibenzocycloheptenes; Benzocycloheptenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 16, 2015
• First Posted: October 22, 2015
• Study Start: December 6, 2015
• Primary Completion: March 1, 2016
• Study Completion: March 1, 2021
• Last Updated: March 10, 2021

Record last verified: 2021-03

Locations

ES (1)