Friedreich Ataxia
Conditions
Interventions
Product Name: Nicotinamide
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: NICOTINAMIDE
CAS Number: 98-92-0
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number:
Sponsors
RWTH Aachen University represented by the Rector himself, represented by the Dean of the Medical Faculty
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. 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 =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. 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. 2. Any uncontrolled medical or neurological/neurodegenerative condition (other than Friedreich ataxia). 3. Clinically significant psychiatric illness (e.g., uncontrolled major depression, schizophrenia, bipolar affective disorder) within 6 months prior to screening. 4. Patients with significant clinical dysphagia. 5. Hypersensitivity to nicotinamide. 6. Patients known to be positive for human immunodeficiency virus (HIV). 7. Patients with a significant history of substance abuse (e.g. alcohol or drug abuse) within the previous six months before enrolment. 8. Patients with a history of severe allergies to medications. 9. 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). 10. 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. 11. History or evidence of an autoimmune disorder considered clinically significant by the Investigator or requiring chronic use of systemic corticosteroids or other immunosuppressants. 12. History of clinically significant cardiac disease (ejection fraction 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). 13. The subject received an investigational drug within 30 days prior to inclusion into this study. 14. Patients taking sodium valproate or any other known histone deacetylase inhibitor. 15. Use of vitamin B1 (thiamine), withdrawal should be at least 3 months prior Screening. 16. Use of vitamin B3 (nicotinamide), withdrawal should be at least 3 months prior Screening. 17. If patients are taking idebenone or coenzyme Q10 (CoQ), this should be stable over the last three months and not changed during the study. 18. The subject is unwilling or unable to provide written informed consent and to follow the procedures outlined in the protocol. 19. 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. 20. Patients participating in another interventional clinical trial, excluding natural history/observational studies, at start of the study or within the last 30 days before study start. 21. The subject is mentally or legally incapacitated. 22. Pregnant females as determined by positive [serum or urine] hCG test at Screening or prior to dosing.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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´s ataxia.;Secondary Objective: To determine the change of secondary endpoints such as quality of life, functional motor and cognitive measures, clinician’s and patient’s global impression-change scales as well as frataxin protein level under treatment of daily doses of nicotinamide as compared with placebo in patients with Friedreich´s ataxia. To evaluate cognition, cardiac and spinal cord/brain measures. ;Primary end point(s): Change in the Scale for the Assessment and Rating of Ataxia (SARA);Timepoint(s) of evaluation of this end point: At screening, baseline, +4 month, +8 month, +12 month, +18 month and +24 month | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) Progression of quality of life measures such as the `Activity of Daily Living´ (ADL) scores, `modified Friedreich ataxia rating scale´ (mFARS) and the EuroQol five dimensions questionnaire (EQ-5D) 2) Progression of `Spinocerebellar Ataxia Functional Index´ (SCAFI) (Schmitz-Hubsch et al., 2008) 3) Progression of `Composite Cerebellar Functional Severity´ (CCFS), which has been validated in children and adults with Friedreich ataxia (Filipovic Pierucci et al., 2015) 4) Progression of `Inventory of Non-Ataxia Signs´ (INAS) (Jacobi et al., 2013) 5) Up-regulation of frataxin protein level 6) Clinician’s Global Impression-Change Scale (CGI-C) 7) Patient’s Global Impression-Change Scale (PGI-C) 8) Safety 9) Progression of the `Montreal Cognitive Assessment´ (MoCA) 10) Active modification of the FXN locus, as measured by chromatin immunoprecipitation and chromosome confirmation capture sequencing 11) Percentual change in left ventricular mass index as measured by echocardiogram 12) Structural and functional changes of the brain and spinal cord, measured by magnetic resonance imaging (MRI) ;Timepoint(s) of evaluation of this end point: 1), 2), 3), 4), 6), 7), 9) at baseline, +4 month, +8 month, +12 month, +18 month and +24 month 5) at baseline, +12 month and +24 month 8) at baseline, +1 month, +4 month, +8 month, +12 month, +18 month and +24 month 10) at baseline, +12 month and +24 month 11) at baseline, +12 month and +24 month 12) at baseline and +24 month | — |
Countries
Austria, Germany
Contacts
Public ContactCTC-A
University Hospital RWTH Aachen
Outcome results
None listed