Assessment of Clemastine Fumarate as a Remyelinating Agent in Multiple Sclerosis

NCT02040298 | Completed Phase 2 Results

• 1 other identifier: ReBUILD
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

The main purpose of this study is to assess clemastine as a remyelinating agent in patients with relapsing forms of multiple sclerosis. The study will also evaluate the tolerability of clemastine, originally approved as first-generation antihistamine, in patients with multiple sclerosis. Study procedures will include assessments for evidence of remyelination in the anterior visual pathway and in the brain using electrophysiologic techniques and magnetic resonance imaging. The study will also assess the robustness and stability of this clinical effect in patients taking clemastine for up to 3 months. Patients in this study can remain on their standard disease modifying treatment during the course of the study. However, patients cannot participate in any other investigational new drug research study concurrently.

Conditions

Multiple Sclerosis, Relapsing-Remitting

Outcome Measures

Primary Outcomes (1)

• Full Field Visual Evoked Potential (VEP)

  The primary objective is to evaluate the efficacy of Clemastine relative to placebo for reducing P100 latencies on full field transient pattern reversal visual evoked potentials.Visual evoked potentials (VEP) are used primarily to measure the functional integrity of the visual pathways from the retina to the visual cortex of the brain. VEP latencies were collected at Baseline, Month 1, Month 3, and Month 5.

  Treatment start to treatment end, up to 3 months.

Secondary Outcomes (3)

• Tolerability of Clemastine in Multiple Sclerosis (MS) Patients

  Treatment start to treatment end, up to 3 months.

• Myelin Water Fraction (MWF) and Magnetization Transfer Ratios (MTR)

  Treatment start to treatment end, up to 3 months.

• Expanded Disability Status Scale (EDSS) Score

  Start of treatment to end of treatment, up to 3 months

Other Outcomes (4)

• Serum Creatinine Level

  Baseline, 1 month, 3 month, 5 month

• Serum Triglyceride Level

  Baseline, 1 month, 3 month, 5 month

• Vitamin B-12 Level

  Baseline, 1 month, 3 month, 5 month

Study Arms (2)

3 months Clemastine, 2 months Placebo

ACTIVE COMPARATOR

4mg clemastine twice daily for first 3 months -- crossover -- equivalent quantity/frequency of placebo for last 2 months

Drug: Clemastine; Drug: Placebo

3 months Placebo , 2 months Clemastine

ACTIVE COMPARATOR

Placebo for first 3 months -- crossover -- 4mg clemastine twice daily for last 2 months.

Drug: Clemastine; Drug: Placebo

Interventions

Clemastine DRUG

4mg tablet twice daily

Also known as: Clemastine Fumarate,, Tavist -1

3 months Clemastine, 2 months Placebo; 3 months Placebo , 2 months Clemastine

Placebo DRUG

Placebo tablet twice daily

3 months Clemastine, 2 months Placebo; 3 months Placebo , 2 months Clemastine

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Relapsing remitting Multiple Sclerosis by 2010 Revised McDonald Criteria
• Age 18-60.
• Latency delay \> 125 milliseconds on baseline full-field transient pattern reversal visual evoked potential (VEP) in at least one eye (electrophysiological evidence of demyelination)
• Retinal nerve fiber layer (RNFL) \> 70 microns on Spectralis Domain Optical Coherence Topography (SD-OCT) in the same eye meeting criteria for latency delay (sufficient axons)
• No optic neuritis in prior 6 months
• Stable immunomodulatory therapy - no switch or planned switch in \> 6 months and no change in doses in 30 days prior to screening
• Use of appropriate contraception during period of trial (females of child bearing potential)
• Understand and sign informed consent.
• Expanded disability status scale (EDSS) 0-6.0 (inclusive)

You may not qualify if:

• Major ophthalmologic disease / Concomitant ophthalmologic disorders (e.g. diabetes, macular degeneration, glaucoma, severe myopia , etc).
• Myopia \> -7 Diopters (Severe myopia)
• History of significant cardiac conduction block
• History of cancer
• Known optic neuritis in involved eye \> 5 years ago OR disease duration \> 15 years
• Suicidal ideation or behaviour in 6 months prior to screening
• Pregnancy, breastfeeding, or planning to become pregnant.
• Involved with other study protocol simultaneously without prior approval. 9. Concomitant use of Dalfampridine (4AP or diamino4AP) or any other formulation of 4AP or diamino4AP.
• Concomitant use of any other putative remyelinating therapy as determined by investigator.
• Treatment with corticosteroids within 30 days prior to screening
• Prior treatment with total lymphoid irradiation, T cell or T cell receptor vaccination
• Prior treatment with alemtuzumab, mitoxantrone, or cyclophosphamide
• Serum creatinine \> 1.5 mg/dL; aspartate aminotransferase (AST), alanine aminotransferase (ALT) or alkaline phosphatase \> 2 times the upper limit of normal
• History of drug or alcohol abuse within the past year
• Untreated vitamin B12 deficiency (as determined by B12 serological assessments and metabolites including methylmalonic acid (MMA) and homocysteine) or untreated hypothyroidism

Sponsors & Collaborators

• University of California, San Francisco: lead

Study Sites (1)

UCSF Multiple Sclerosis Center

San Francisco, California, 94518, United States

Location

Related Publications (3)

• Fischer JS, LaRocca NG, Miller DM, Ritvo PG, Andrews H, Paty D. Recent developments in the assessment of quality of life in multiple sclerosis (MS). Mult Scler. 1999 Aug;5(4):251-9. doi: 10.1177/135245859900500410.

  PMID: 10467384 BACKGROUND

• Green AJ, Gelfand JM, Cree BA, Bevan C, Boscardin WJ, Mei F, Inman J, Arnow S, Devereux M, Abounasr A, Nobuta H, Zhu A, Friessen M, Gerona R, von Budingen HC, Henry RG, Hauser SL, Chan JR. Clemastine fumarate as a remyelinating therapy for multiple sclerosis (ReBUILD): a randomised, controlled, double-blind, crossover trial. Lancet. 2017 Dec 2;390(10111):2481-2489. doi: 10.1016/S0140-6736(17)32346-2. Epub 2017 Oct 10.

  PMID: 29029896 RESULT

• Abdelhak A, Cordano C, Boscardin WJ, Caverzasi E, Kuhle J, Chan B, Gelfand JM, Yiu HH, Oertel FC, Beaudry-Richard A, Condor Montes S, Oksenberg JR, Lario Lago A, Boxer A, Rojas-Martinez JC, Elahi FM, Chan JR, Green AJ. Plasma neurofilament light chain levels suggest neuroaxonal stability following therapeutic remyelination in people with multiple sclerosis. J Neurol Neurosurg Psychiatry. 2022 Jun 16:jnnp-2022-329221. doi: 10.1136/jnnp-2022-329221. Online ahead of print.

  PMID: 35710320 DERIVED

Related Links

• ReBUILD trial description University of California, San Francisco Multiple Sclerosis Center

MeSH Terms

Conditions

Multiple Sclerosis, Relapsing-Remitting

Interventions

Clemastine

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

Intervention Hierarchy (Ancestors)

Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Tracy Tran, BA
• Organization: UCSF

tracy.tran@ucsf.edu

415-353-2707

Study Officials

• Ari J. Green, MD, MCR

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 10, 2014
• First Posted: January 20, 2014
• Study Start: January 1, 2014
• Primary Completion: September 1, 2015
• Study Completion: April 1, 2016
• Last Updated: September 17, 2025
• Results First Posted: July 15, 2021

Record last verified: 2025-09

Locations

US (1)