A double-blind, randomized, placebo-controlled trial to test the efficacy, safety and tolerability of Dimethyl Fumarate in Friedreich Ataxia (DMF-FA-201).

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Dipartimento Di Neuroscienze E Scienze Riproduttive Ed Odontostomatologiche Universita Degli Studi Di Napoli Federico II

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

10 Nov 2023 → ongoing

Decision date (initial)

2023-05-03

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

ALMIRALL S.A. · AIFA

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Efficacy, Safety

To test the effect of DMF on FXN transcription and frataxin protein in FRDA patients.

Secondary objectives 1

1. To test the effect of DMF on the nrf2 pathway, on mitochondrial biogenesis, safety and tolerability, and clinical aspects of the disease.

Conditions and MedDRA coding

Friedreich's Ataxia

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Molecular diagnosis of Friedreich Ataxia with a homozygous GAA expansion
2. Age ≥12 years
3. Body weight ≥30 Kg
4. Patients able to read and sign the informed consent

Exclusion criteria 13

1. Treatment with DMF in the previous 12 months
2. Treatment with Idebenone, coenzyme Q10, or any other vitamin supplements in the previous 30 days
3. Patients in treatment with any other not allowed drug
4. Any Cardiac and/or Renal and/or Hepatic disease judged as clinically significant by the investigator (any abnormal and clinically non significant cardiac disease associated with Friedreich Ataxia is not an exclusion criteria)
5. Any clinically significant ECG abnormalities that may interfere with the study
6. Any abnormal and clinically significant laboratory exams at screening visit that may interfere with the trial
7. Any acute disease that could interfere with the study, as judged by the investigator
8. Patient positive to the Human Immunodeficiency Virus (HIV) or Hepatitis B or C test
9. Patients with a positive history of neoplasia, with the only exception of a completely excided basal cell carcinoma
10. Positive history of alcohol or drug abuse in the past 2 years, except for medical use of cannabis
11. Hypersensitivity to DMF or any other component of the study drug
12. Patients not able to comply with the study
13. For female patients (Sexually not active, hysterectomized, sterilized, menopause patients are excluded from the following criteria): - Pregnancy, or - Breastfeeding, or - Inadequate contraception

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The effect of DMF compared to placebo on one of two co-primary endpoints (achievement of one out of two is a positive result): FXN gene expression and frataxin protein level. For both we will consider the change from baseline to 12 weeks (core phase of the DMF-FA-201 study).

Secondary endpoints 10

1. Effect of DMF on the cardiopulmonary exercise outputs (VO2max, anaerobic threshold, peak workload)
2. Effect of DMF on echocardiographic measures
3. Effect of DMF on FXN and frataxin protein from pooled data from the core and extension phase of the study
4. Effect of DMF on FXN and frataxin protein at week 4 of the core phase
5. Effect of DMF on Nrf2 pathway genes: NFE2L2, NQO1, HMOX1, PDLIM1, NCF2
6. Effect of DMF on mitochondrial biogenesis genes (mt-ND6, mtCYB, mt-CO2, mt-ATP6) and on mtDNA/nDNA
7. Number and distribution of serious and non-serious adverse events between DMF and placebo
8. Difference in the Scale for the Rating and assessment of Ataxia (SARA) and modified Friedreich Ataxia Rating Scale (mFARS) between DMF and placebo
9. Difference in the 9-hole pegboard test (9HPT) between DMF and placebo
10. Difference in the EQ-5D and ADL/IADL between DMF and placebo

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Dipartimento Di Neuroscienze E Scienze Riproduttive Ed Odontostomatologiche Universita Degli Studi Di Napoli Federico II

Sponsor organisation

Dipartimento Di Neuroscienze E Scienze Riproduttive Ed Odontostomatologiche Universita Degli Studi Di Napoli Federico II

Address

Via Sergio Pansini 5

City

Naples

Postcode

80131

Country

Italy

Scientific contact point

Organisation

Dipartimento Di Neuroscienze E Scienze Riproduttive Ed Odontostomatologiche Universita Degli Studi Di Napoli Federico II

Contact name

Francesco Saccà

Public contact point

Organisation

Dipartimento Di Neuroscienze E Scienze Riproduttive Ed Odontostomatologiche Universita Degli Studi Di Napoli Federico II

Contact name

Francesco Saccà

Third parties 1

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 11 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications