Dimethyl Fumarate in Adrenomyeloneuropathy

NCT06513533 | Recruiting Phase 2

• 2 other identifiers: XAMNDMFAP20222021-003826-65
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 3

Brief Summary

The goal of this clinical trial is to determine if dimethyl fumarate is effective in treating motor problems in adults with Adrenomyeloneuropathy. The trial will also assess the safety of dimethyl fumarate and explore the molecular mechanisms underlying the disease. The primary questions it aims to answer are:

• Does dimethyl fumarate improve motor problems in participants?
• What medical issues do participants experience while taking dimethyl fumarate? Researchers will compare the effects of dimethyl fumarate to a placebo (a substance that looks like the drug but contains no active ingredients) to evaluate its effectiveness in treating Adrenomyeloneuropathy. Participants will:
• Take either dimethyl fumarate or a placebo daily for 36 months.
• Visit the clinic at the start of the trial, then at 3 months, 6 months, and every 6 months thereafter for checkups and tests.

Conditions

Adrenomyeloneuropathy Without Cerebral Involvement

Outcome Measures

Primary Outcomes (3)

• Postural sway test

  Balance is assessed with static posturography by measuring the extent of postural sway in four conditions, each for two 20-second trials: (1) eyes open feet shoulder width apart (EOFA), (2) eyes closed feet shoulder width apart (ECFA), (3) eyes open feet together (EOFT), and (4) eyes closed feet together (ECFT)

  Interim analysis 1 (at 12 months of treatment)

• Postural sway test

  Balance is assessed with static posturography by measuring the extent of postural sway in four conditions, each for two 20-second trials: (1) eyes open feet shoulder width apart (EOFA), (2) eyes closed feet shoulder width apart (ECFA), (3) eyes open feet together (EOFT), and (4) eyes closed feet together (ECFT)

  Final analysis 1 (at 24 months of treatment)

• Postural sway test

  Balance is assessed with static posturography by measuring the extent of postural sway in four conditions, each for two 20-second trials: (1) eyes open feet shoulder width apart (EOFA), (2) eyes closed feet shoulder width apart (ECFA), (3) eyes open feet together (EOFT), and (4) eyes closed feet together (ECFT)

  Final analysis 2 (at 36 months of treatment)

Secondary Outcomes (27)

• 2 Minute Walk Test (2MWT)

  Interim analysis 1 (at 6 months of treatment)

• 2 Minute Walk Test (2MWT)

  Interim analysis 2 (at 12 months of treatment)

• 2 Minute Walk Test (2MWT)

  Final analysis 1 (at 24 months of treatment)

• 2 Minute Walk Test (2MWT)

  Final analysis 2 (at 36 months of treatment)

• 6 Minute Walk Test (6MWT)

  Interim analysis 1 (at 6 months of treatment)

Study Arms (2)

DMF arm

EXPERIMENTAL

Oral administration of dimethyl fumarate, 480 mg/day, for 36 months

Drug: Dimethyl fumarate

Placebo arm

PLACEBO COMPARATOR

Oral administration of placebo for 24 months, followed by oral dimethyl fumarate, 480 mg/day for 12 months

Other: Placebo

Interventions

Placebo OTHER

1 tablet twice daily (one in the morning and one in the evening) for the first 7 days as a starter dose followed by 2 tablets (240 mg) twice daily

Placebo arm

Dimethyl fumarate DRUG

1 tablet twice daily (one in the morning and one in the evening) for the first 7 days as a starter dose followed by 2 tablets (240 mg) twice daily

Also known as: Skilarence, Tecfidera

DMF arm

Eligibility Criteria

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

You may qualify if:

• elevated plasma VLCFA
• ABCD1 gene mutation identified
• Clinical signs of AMN with at least pyramidal signs in the lower limbs and difficulties to walk (EDSS score ≥ 2.0 and ≤ 6.5). EDSS score will also be re-evaluated at M12, M24 and M36.
• Normal brain MRI or brain MRI showing:
• abnormalities that can be observed in AMN patients without cerebral demyelination with a maximum Loes score of 4
• and/or stable (≥ 6 months) cerebral demyelination without gadolinium enhancement with a Loes score ≤ 12
• Appropriate steroid replacement if adrenal insufficiency is present
• Potential childbearing women should use an adequate method of contraception to avoid pregnancy throughout the study to minimize the risk of pregnancy. If oral contraceptives are used, the use of an alternative barrier method is recommended.
• Likely to be able to participate in all scheduled evaluations and complete all required study procedures
• Signed and dated written informed consent to participate in the study in accordance with local regulations

You may not qualify if:

• Any progressive neurological disease other than AMN
• Leukopenia below 3.0x109/L, lymphopenia below 0.5x109/L or other pathological results in the complete blood count
• Suspected or confirmed progressive multifocal leukoencephalopathy (PML)
• Severe gastrointestinal disease
• Uncontrolled hepatic, renal or cardiovascular disease, or any evolutive malignancy
• Pregnancy and breast-feeding in woman and potential childbearing woman unable or unwilling to use an acceptable contraceptive method during the study
• Contra-indications for MRI procedure such as subjects with paramagnetic materials in the body as aneurysm clips, pacemakers, intraocular metal or cochlear implants
• Not easily contactable by the investigator in case of emergency or not able to call the investigator

Sponsors & Collaborators

• Pujol, Aurora, M.D.: lead
• Instituto de Salud Carlos III: collaborator
• Spanish Clinical Research Network - SCReN: collaborator
• Institut d'Investigació Biomèdica de Bellvitge: collaborator

Study Sites (3)

Bellvitge University Hospital

L'Hospitalet de Llobregat, Barcelona, 08907, Spain

RECRUITING

Donostia University Hospital

Donostia / San Sebastian, 20014, Spain

NOT YET RECRUITING

University Hospital 12 de Octubre

Madrid, 28041, Spain

RECRUITING

MeSH Terms

Interventions

Dimethyl Fumarate

Intervention Hierarchy (Ancestors)

Fumarates; Dicarboxylic Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals

Study Officials

• Carlos Casasnovas, MD, PhD

  Bellvitge University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Aurora Pujol, MD, PhD

CONTACT

+34936073800; apujol@idibell.cat

Stéphane Fourcade, PhD

CONTACT

+34936073800; sfourcade@idibell.cat

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Group 1: oral administration of dimethyl fumarate for 36 months Group 2: oral administration of placebo for 24 months, followed by oral dimethyl fumarate for 12 months.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDIV
• Responsible Party: SPONSOR

Model Details: Double-arm, randomized, placebo-controlled, multicentric trial

Study Record Dates

• First Submitted: July 17, 2024
• First Posted: July 22, 2024
• Study Start: April 23, 2024
• Primary Completion (Estimated): March 31, 2028
• Study Completion (Estimated): June 30, 2028
• Last Updated: July 25, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

ES (3)