- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03761511
Study of the Efficacy and Safety of Nicotinamide in Patients With Friedreich Ataxia (NICOFA)
A Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicentre Study of the Efficacy and Safety of Nicotinamide in Patients With Friedreich Ataxia
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Phase
- Phase 2
Contacts and Locations
Study Locations
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Innsbruck, Austria, 6020
- Medical University Innsbruck
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Contact:
- Sylvia Boesch, PD Dr.
- Email: sylvia.boesch@i-med.ac.at
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Paris, France, 75646
- Service de génétique médicale - Hôpital La Pitié Salpetrière
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Contact:
- Alexandra Durr, Prof. Dr.
- Phone Number: : +33 (0) 1 57 27 40 00
- Email: alexandra.durr@upmc.fr
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Aachen, Germany, 52074
- University Hospital RWTH Aachen
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Contact:
- Jörg B. Schulz, Univ.-Prof.
- Email: jschulz@ukaachen.de
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Milano, Italy, 20133
- Fondazione IRCCS Istituto Neurologico Carlo Besta
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Contact:
- Caterina Mariotti, Prof. Dr.
- Email: Caterina.Mariotti@istituto-besta.it
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Madrid, Spain, 28046
- Hospital Universitario La Paz
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Contact:
- Francisco Javier Rodríguez de Rivera Garrido, Prof. Dr.
- Email: frriveragarrido@salud.madrid.org
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London, United Kingdom, WC1N 3BG
- University College London
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Contact:
- Paola Giunti, Prof. Dr.
- Email: p.giunti@ucl.ac.uk
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London, United Kingdom, W12 0HS
- Imperial College London
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Patients must have a molecular genetic diagnosis of Friedreich ataxia with a GAA- repeat expansion on both alleles of the FXN gene and a SARA Score >7 and <28 and age <50 years.
- Patients must be ≥18 years old and have a weight of at least 50kg.
- Written informed consent prior to study participation
- A female subject is eligible to participate if she is of: Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea or of childbearing potential and agrees to
Exclusion Criteria:
- Patients with any medical condition or illness that, in the opinion of the investigator would interfere with study compliance and/or impair the patient´s ability to participate or complete the study.
- Any uncontrolled medical or neurological/neurodegenerative condition (other than Friedreich ataxia).
- Clinically significant psychiatric illness (e.g., uncontrolled major depression, schizophrenia, bipolar affective disorder) within 6 months prior to screening.
- Patients with significant clinical dysphagia.
- Hypersensitivity to nicotinamide.
- Patients known to be positive for human immunodeficiency virus (HIV).
- Patients with a significant history of substance abuse (e.g. alcohol or drug abuse) within the previous six months before enrolment.
- Patients with a history of severe allergies to medications.
- Indication of impaired liver function as shown by an abnormal liver function profile at screening (e.g., repeated values of aspartate aminotransferase [AST], alanine aminotransferase [ALT] and bilirubin ≥3 × the upper limit of normal).
History of malignancy or carcinoma. The following exceptions may be made after discussion with the Sponsor:
- Subjects with cancers in remission more than 5 years prior to screening.
- Subjects with a history of excised or treated basal cell or squamous carcinoma.
- Subjects with prostate cancer in situ.
- History or evidence of an autoimmune disorder considered clinically significant by the Investigator or requiring chronic use of systemic corticosteroids or other immunosuppressants.
- The subject has a history of any other illness, which, in the opinion of the Investigator, might pose an unacceptable risk by administering study medication.
- History of clinically significant cardiac disease (ejection fraction < 40% [normal range 50-70%], cardiac insufficiency defined as New York Heart Association [NYHA] Class >2; clinically significant congenital or acquired valvular disease; symptomatic coronary disease such as prior myocardial infarction or angina, B-type natriuretic peptide (BNP) level increase more than 2 x of the normal age- and gender dependent range; history of unstable arrhythmias, history of atrial fibrillation).
- The subject received an investigational drug within 30 days prior to inclusion into this study.
- Patients taking sodium valproate, tranylcypromine or any other known histone deacetylase inhibitor.
- Use of vitamin B1 (thiamine), withdrawal should be at least 3 months prior screening or 5 half-lives, whichever is longer.
- Use of vitamin B3 (nicotinamide), withdrawal should be at least 3 months prior screening.
- If patients are taking idebenone or coenzyme Q10 (CoQ), this should be stable over the last three months and not changed during the study.
- The subject is unwilling or unable to provide written informed consent and to follow the procedures outlined in the protocol.
- For subjects who will undergo an MRI: Any contraindications to MRI such as, but not limited to cardiac pacemaker, implanted cardiac defibrillator, aneurysm clips, carotid artery vascular clamp, neurostimulator, implanted drug infusion devices, metal fragments or foreign objects in the eyes, skin or body, bone growth/fusion stimulator, cochlear, otologic implant, severe claustrophobia or any condition that would counterindicate an MRI scan.
- Patients participating at start or have been within 30 days before start of study in another pharmacological and non-pharmacological clinical trial, excluding natural history / observational studies.
- The subject is mentally or legally incapacitated.
- Pregnant females as determined by positive [serum or urine] hCG test at Screening or prior to dosing. Participants of child-bearing age should use adequate contraception as defined in the study protocol.
- Lactating females.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Active Comparator: Treatment arm
Nicotinamide 4 g (capsules) or highest tolerated dose with a minimum of 2 g/d per os once daily
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Nicotinamide 4 g (capsules) or highest tolerated dose with a minimum of 2 g/d per os once daily
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Placebo Comparator: Placebo arm
Matching Placebo (capsules) once daily
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Matching Placebo (capsules) once daily
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Scale for the Assessment and Rating of Ataxia (SARA)
Time Frame: 1 year
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The primary objective of the study is to evaluate the efficacy of daily doses of nicotinamide in slowing disease progression as measured by changes in the Scale for the Assessment and Rating of Ataxia (SARA) as compared with placebo in patients with Friedreich ataxia. The SARA is a tool for assessing ataxia. It has eight categories with accumulative score ranging from 0 (no ataxia) to 40 (most severe ataxia). When completing the outcome measure each category is assessed and scored accordingly. Scores for the eight items range as follows: Gait (0-8 points), Stance (0-6 points), Sitting (0-4 points) Speech disturbance (0-6 points) Finger chase (0-4 points) Nose-finger test (0-4 points) Fast alternating hand movement (0-4 points) Heel-shin slide (0-4 points) Once each of the 8 categories have been assessed, the total is calculated to determine the severity of ataxia. |
1 year
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Progression of quality of life measures via questionnaire EuroQol five dimensions questionnaire (EQ-5D)
Time Frame: 1 year
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This is a generic instrument, developed and validated by the EuroQoL Group (1990), in which the patient self-rates in particular his/her health status on a visual analogue scale (VAS); the best score is 100.
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1 year
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Modified Friedreich Ataxia Rating Scale (mFARS)
Time Frame: 1 year
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Modified FARS scores are defined as the sum of scores for bulbar function, upper limb coordination, lower limb coordination, and upright stability.
The mFARS consists of three subscales, comprising a general score for ataxia, a score for activities of daily living and a neurological examination.
The scores can be added to make a total score ranging from 0 to 159.
A higher score indicates a greater level of disability.
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1 year
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Progression of cerebellar severity measured by 'Composite Cerebellar Functional Severity´ (CCFS) score
Time Frame: 1 year
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CCFS includes two tests performed with the dominant hand,named the click test and the 9 holes pegboard test (9HPT).
An electronic device was created to perform CCFS and to calculate the Z score by subtracting the expected time
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1 year
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Clinician's Global Impression-Change Scale (CGI-C) including comparison of change to the last visit
Time Frame: 1 year
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The Clinical Global Impression - Improvement scale (CGI-I) is a 7 point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention.
and rated as: 1. Very much improved; 2. Much improved; 3. Minimally improved; 4. No change; 5. Minimally worse; 6.
Much worse; 7. Very much worse
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1 year
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Safety issues measured by appearance of AEs/SAEs
Time Frame: 1 year
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AEs may be volunteered spontaneously by the patient, or discovered as a result of general non-directed questioning by the study personnel or by physical examination.
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1 year
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Collaborators and Investigators
Sponsor
Collaborators
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Metabolic Diseases
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Neurologic Manifestations
- Genetic Diseases, Inborn
- Neurodegenerative Diseases
- Dyskinesias
- Spinal Cord Diseases
- Heredodegenerative Disorders, Nervous System
- Mitochondrial Diseases
- Cerebellar Diseases
- Spinocerebellar Degenerations
- Ataxia
- Cerebellar Ataxia
- Friedreich Ataxia
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Vasodilator Agents
- Antimetabolites
- Micronutrients
- Hypolipidemic Agents
- Lipid Regulating Agents
- Vitamins
- Vitamin B Complex
- Nicotinic Acids
- Niacinamide
- Niacin
Other Study ID Numbers
- 15-138
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Study Data/Documents
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Study Protocol
Information identifier: NICOFA
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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