A trial to determine bexarotene's safety and tolerability and it's ability to promote brain repair in patients with multiple sclerosis.

• Register: EUCTR
• Last refreshed on: 2 June 2020
• Main ID: EUCTR2014-003145-99-GB
• Date of registration: 19/01/2015
• Prospective Registration: Yes
• Primary sponsor: Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge
• Public title: A trial to determine bexarotene's safety and tolerability and it's ability to promote brain repair in patients with multiple sclerosis.
• Scientific title: A randomised placebo-controlled study of the safety and tolerability of a retinoid-X receptor agonist's ability to promote remyelination in people with relapsing-remitting multiple sclerosis already on interferon-beta therapy: a phase 2a trial - CCMR One
• Date of first enrolment: 19/03/2015
• Target sample size: 50
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-003145-99
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

United Kingdom

Contacts

• Name: Clinical Trials Regulatory Manager
• Affiliation: Cambridge Clinical Trials Unit

• Name: Clinical Trials Regulatory Manager
• Affiliation: Cambridge Clinical Trials Unit

Key inclusion & exclusion criteria

Inclusion criteria:
- Informed consent
- Male or female aged between 30 and 50 years inclusive
- Relapsing remitting multiple sclerosis as per the McDonald 2010 criteria, including an MRI satisfying the radiological criteria
- At least five T2 lesions, attributable to MS, on baseline MRI brain scan
- Kurtzke EDSS 3.0-6.0
- At least one relapse in the two years prior to screening
- At the time of screening (and for at least the last 6 months) being treated with interferon-beta (any preparation)
- Able and willing to comply with all study requirements

Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 50
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

Exclusion criteria:
Patients who are:
- Pregnant, lactating or planning pregnancy during course of trial
- Female and male participants unwilling or unable to use two reliable non-hormonal methods of contraception during the course of the trial and for one month thereafter
- Taking gemfibrozil
- Taking disease-modifying therapy for multiple sclerosis, other than interferon-beta within the previous six months
- Significant renal or hepatic impairment (Grade III or worse)
- Known hypersensitivity to bexarotene or to any of the excipients of the product
- Unwillingness to take a product containing gelatin
- Known reaction to gadolinium (within the contrast agent used for MRI scans)
- History of pancreatitis
- Fasting triglycerides over 2.3 mmol/L or baseline dyslipidaemia requiring treatment
- Known hypervitaminosis A
- Uncontrolled thyroid disease
- Excessive alcohol consumption (>24units/week for men, >14 units/week for women)
- Uncontrolled diabetes mellitus
- Biliary tract disease
- Hereditary fructose intolerance
- Use of CYP3A4-substrates (ketoconazole, itraconazole, protease inhibitors, clarithromycin and erythromycin) or CYP3A4-inducers (rifampicin, phenytoin, dexamethasone or phenobarbital), unless patients are willing to stop these (and it is safe to do so)
- Any other significant disease, disability or investigation result which, in the opinion of the Investigator, may either put the participant at risk because of participation in the study, or may influence the result of the study, or the participant’s ability to participate in the study.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Relapsing-remitting multiple sclerosis already on interferon-beta therapy
MedDRA version: 17.1 Level: PT Classification code 10028245 Term: Multiple sclerosis System Organ Class: 10029205 - Nervous system disorders

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Intervention(s)

Trade Name: Targretin
Product Name: Bexarotene
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Bexarotene
CAS Number: 153559-49-0
Concentration unit: mg/m2 milligram(s)/square meter
Concentration type: range
Concentration number: 100-300
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): The primary endpoint is adverse events and withdrawals atributable to taking bexarotene.

Secondary Objective: The secondary objective is to assess the efficacy of bexarotene in promoting myelin repair (remyelination) in relapsing remitting multiple sclerosis.

Exploratory objectives seek to assess bexarotene's effect on:
-lesions of different ages and severities;
-optic nerve function (giving a functional measure of whether a damaged (demyelinated) optic nerve may have remyelinated after bexarotene);
-patients' level of disability;
-immune markers in patient's bloods during and after treatment.

Timepoint(s) of evaluation of this end point: At the end of the 6 months of treatment.

Main Objective: The primary objective is to establish the safety and tolerability of bexarotene in the treatment of relapsing remitting multiple sclerosis.

Secondary Outcome(s)

Secondary end point(s): The secondary endpoint is mean lesional Magnetisation Transfer Ratio (MTR) between month 0 and month 6 for lesions selected for each patient whose MTR lies below the within-patient median.

Timepoint(s) of evaluation of this end point: After 6 months of treatment

Secondary ID(s)

CCMROne

Ethics review

Status: Approved
Approval date: 19/03/2015
Contact: