Friedreich Ataxia
Conditions
Brief summary
To evaluate the safety and tolerability of single ascending doses of CTI-1601 in participants with Friedreich's ataxia
Detailed description
Single Ascending Dose (SAD), Double-Blind, Placebo Controlled Study. To evaluate the safety and tolerability of single ascending doses of CTI-1601 in subjects with Friedreich's ataxia. Secondary Objectives: 1. To evaluate the pharmacokinetics (PK) of CTI-1601 following increasing single doses of subcutaneously (SC) administered CTI-1601. 2. To evaluate the pharmacodynamics (PD) of CTI-1601 following increasing single doses of SC administered CTI-1601. CTI-1601 or Placebo - Dose/Mode of Administration: Single Dose/Subcutaneous
Interventions
BIOLOGICALCTI-1601
CTI-1601 is a recombinant fusion protein and is intended to deliver human frataxin, the protein deficient in Friedreich's ataxia
BIOLOGICALPlacebo
Placebo Comparator
Sponsors
Veristat, Inc.
Metrum Research Group, LLC
Larimar Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Subject has genetically confirmed Friedreich's ataxia diagnosis, homozygous GAA repeat expansions, with repeat sizing (if available) included on diagnostic report. 2. Subject is male or female, 18 years of age or older at screening. 3. Subject must have a mFARS\_neuro score ≥ 20 and be able to traverse a distance of 25 feet with or without some assistive device (cane, walker, crutches, self-propelled wheelchair) and (a) be able to sit upright with thighs together and arms crossed without requiring support on more than two sides; (b) be able to transfer from bed to chair independently or with minimal assistance if, in the opinion of the investigator, the degree of physical disability does not result in undue risk to the subject while participating in the study; and (c) perform basic daily care, such as feeding themselves and personal hygiene, with minimal assistance. 4. Subjects must weigh \> 40 kilograms (kg).
Exclusion criteria
1. Subjects who are confirmed as compound heterozygous (GAA repeat expansion on only one allele) for Friedreich's ataxia. 2. Subject requires use of amiodarone. 3. Subject used erythropoietin, etravirine, or gamma interferon within 3 months prior to screening. 4. Subject use of investigational drug (other than CTI-1601) or device within 90 days prior to screening. 5. Subject use of daily biotin supplementation that exceeds 30 mcg/day, either as part of a multivitamin or as a standalone supplement, within 7 days prior to study drug administration and/or throughout the entire study. 6. Subject has clinically significant arrhythmia on electrocardiogram (ECG), or evidence of predisposition to significant ventricular arrhythmia on ECG, or evidence of active and unstable coronary artery disease. 7. Male subject who has an ECG QTcF \> 450 milliseconds or female subject who has an ECG QTcF \> 470 milliseconds. 8. Subject has a screening echocardiogram ejection fraction \<45 percent. 9. Subject has a history of aspiration, aspiration pneumonia, or recurrent episodes of pneumonia (greater than or equal to 2 episodes of pneumonia) within the last 12 months. 10. Subjects with known or suspected chronic use of cannabinoid products.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants with Treatment-Emergent Adverse Events | Through study completion, an average of 70 days | Overall summary of the Participants with Treatment Emergent Adverse Events |
| Number of Treatment Emergent Adverse Events by System Organ Classification and Preferred Term | Through study completion, an average of 70 days | Overall summary of Participants with Treatment Emergent Adverse Events by System Organ Classification (MedDRA version 22.0) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics - Time to reach maximum plasma concentration after a single dose | Up to 48 hours | Summary assessment of changes in time to reach maximum plasma concentration after a single dose |
| Pharmacokinetics - Area under the concentration-time curve from time 0 to infinity | 48 hours | Summary assessment of changes in the area under the concentration-time curve from time 0 to infinity |
| Pharmacokinetics - Area under the concentration-time curve from time 0 to the last measurable time point | 48 hours | Summary assessment of changes in the Area under the concentration-time curve from time 0 to the last measurable time point |
| Pharmacokinetics - Apparent total plasma clearance | 48 hours | Summary assessment of changes in the apparent total plasma clearance |
| Pharmacokinetics - Area under the concentration-time curve after a single dose | Up to 48 hours | Summary assessment of changes in the area under the concentration-time curve after a single dose |
| Pharmacokinetics - Apparent volume of distribution | 48 hours | Summary assessment of changes in the apparent volume of distribution |
| Changes from Baseline in Frataxin Levels in Buccal Cells | At baseline and up to 10 days | Summary assessment of changes in frataxin levels in buccal cells |
| Changes from Baseline in Frataxin Levels in Whole Blood | At baseline and up to 10 days | Summary assessment of changes in frataxin levels in whole blood |
| Changes in Gene Expression Profiling | At baseline and up to 10 days | Summary assessment of changes in gene expression levels |
| Pharmacokinetics - Terminal half-life estimation | 48 hours | Summary assessment of changes in the terminal half-life estimation |
| Pharmacokinetics - Maximum observed plasma concentration after a single dose | Up to 48 hours | Summary assessment of changes in the maximum observed plasma concentration after a single dose |
Countries
United States
Outcome results
None listed