Pilot study of safety and efficacy of nicotinamide (vitamin B3) in OPA1 Dominant Optic Atrophy - NICOPA1-TOL

2023-506214-52-00 Therapeutic confirmatory (Phase III) Ended

Start 27 Dec 2023 · End 14 Apr 2026 · Status Ended · 1 EU/EEA countries · 1 sites

Overview

Sponsor-declared trial summary

Phase Therapeutic confirmatory (Phase III)
Status Ended
Participants planned 25
Countries 1
Sites 1

Dominant Optic Atrophy

The main objective is to evaluate the tolerability of 3 grams per day of nicotinamide in DOA/DOA+ patients to ensure that this treatment does not induce ophthalmological or neurological toxic side effects.

Key facts

Sponsor
Centre Hospitalier Universitaire D Angers
Participant type
Patients
Age range
18-64 years, 65+ years
Gender
Male and Female
Therapeutic area
Diseases [C] - Nervous System Diseases [C10]
Trial duration
27 Dec 2023 → 14 Apr 2026
Decision date (initial)
2023-09-13
Transition trial
No
Low-intervention
No
Rare-disease indication
No
Vulnerable population
No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

The main objective is to evaluate the tolerability of 3 grams per day of nicotinamide in DOA/DOA+ patients to ensure that this treatment does not induce ophthalmological or neurological toxic side effects.

Secondary objectives 4

  1. To evaluate the efficacy of treatment on visual function by electroretinogram, measuring visual acuity, visual field and thickness of visual fibers in the optic disc using OCT (optical coherence tomography).
  2. Biological efficacy will be assessed by measuring nicotinamide levels in patients' blood (plasma and whole blood) at baseline and follow-up.
  3. To evaluate the effectiveness of treatment on patients' quality of life using the NEI VFQ 25 self-questionnaire.
  4. To evaluate the neurological efficacy of treatment in DOA+ forms.

Conditions and MedDRA coding

Dominant Optic Atrophy

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

  1. Major patients
  2. Patients with DOA or DOA+ due to a heterozygous pathogenic variant in the OPA1 gene
  3. Nicotinamide-naïve patients (> 3 months)
  4. Patients able to take oral medication, and comply with specific study procedures
  5. Patients affiliated with or benefiting from a social security scheme
  6. Signature of voluntary, free and informed consent to participate in the study

Exclusion criteria 10

  1. Asymptomatic patients (= healthy carriers of an OPA1 mutation who have not developed optic neuropathy)
  2. Patients with other associated severe ophthalmological pathologies (advanced glaucoma, retinal pathology).
  3. Patients treated with Idebenone
  4. Patients with transaminase levels (ASAT and/or ALAT) twice the high normal value
  5. Pregnant, breast-feeding or parturient women
  6. Patients with a contraindication to nicotinamide
  7. Person deprived of liberty by administrative or judicial decision
  8. Patients under legal protection
  9. Persons under compulsory psychiatric care
  10. Persons unable to give consent

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. The primary endpoint will be assessed by the number of patients with reported ophthalmological and/or neurological adverse events.

Secondary endpoints 4

  1. Number of patients with improved visual function at follow-up visits compared with baseline at inclusion.
  2. Increase in plasma and whole blood nicotinamide levels in all patients, comparing baseline at inclusion with two follow-up periods.
  3. Differences on the NEI-VFQ-25 scale between M0 and M6
  4. Clinical neurological improvement at follow-up visits compared with baseline at inclusion.

Investigational products

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

Test 1

NICOBION 500 mg, comprimé pelliculé

PRD352725 · Product

Active substance
Nicotinamide
Pharmaceutical form
FILM-COATED TABLET
Route of administration
ORAL
Max daily dose
3 g gram(s)
Max total dose
3 g gram(s)
Max treatment duration
6 Month(s)
Authorisation status
Authorised
ATC code
A11HA01 — NICOTINAMIDE
Marketing authorisation
223 822-0
MA holder
TEOFARMA S.R.L.
MA country
France
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire D Angers

Sponsor organisation
Centre Hospitalier Universitaire D Angers
Address
4 Rue Larrey
City
Angers Cedex 9
Postcode
49933
Country
France

Scientific contact point

Organisation
Centre Hospitalier Universitaire D Angers
Contact name
coordinating investigator

Public contact point

Organisation
Centre Hospitalier Universitaire D Angers
Contact name
coordinating investigator

Locations

1 EU/EEA country · 1 investigational sites

By country

CountryMS statusPlanned subjectsSites
France Ended 25 1
Rest of world 0

Investigational sites

France

1 site · Ended
Centre Hospitalier Universitaire D Angers
Biochemistry and molecular biology, 4 Rue Larrey, 49100, Angers

Country notifications

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

Country Trial startTrial end Recruitment startRecruitment end Early termination
France 2023-12-27 2026-04-14 2024-01-23 2025-10-14

Results and documents

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

Documents 10 files

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

TypeTitleVersion
Protocol (for publication) D1_Protocol_2023-506214-52-00 3
Protocol (for publication) D4_ Patient facing documents_Questionnaire DN4 1
Protocol (for publication) D4_ Patient facing documents_Questionnaire NEI-VFQ-25 1
Protocol (for publication) D4_Patient facing documents_Carnet patient 2
Protocol (for publication) D4_Patient facing documents_Carnet patient_Tracked changes 2
Recruitment arrangements (for publication) K-Recruitment and Informed consent procedure 1
Subject information and informed consent form (for publication) L1_SIS and ICF_ patient CHU Angers 3
Subject information and informed consent form (for publication) L1_SIS and ICF_ patient hors CHU Angers 3
Summary of Product Characteristics (SmPC) (for publication) SmPC_Nicobion 1
Synopsis of the protocol (for publication) D1_Protocol synopsis_2023-506214-52-00 3

Application history

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

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2023-06-09 France Acceptable
2023-09-12
2023-09-13
2 SUBSTANTIAL MODIFICATION SM-1 2024-10-18 France Acceptable
2024-12-16
2024-12-19