Friedreich Ataxia
Conditions
Brief summary
To evaluate the safety and tolerability of multiple ascending doses of CTI-1601 in participants with Friedreich's ataxia
Detailed description
Multiple Ascending Dose (MAD), Double-Blind, Placebo Controlled Study. To evaluate the safety and tolerability of multiple ascending doses of CTI-1601 in subjects with Friedreich's ataxia. Secondary Objectives: 1. To evaluate the pharmacokinetics (PK) of CTI-1601 following, multiple, increasing, doses of subcutaneously (SC) administered CTI-1601. 2. To evaluate the pharmacodynamics (PD) of CTI-1601 following, multiple, increasing, doses of SC administered CTI-1601.
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 manifested by 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 assistance if, in the opinion of the principal 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 had a serious adverse event (SAE), an adverse event (AE) that is Grade 3 or higher according to the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 (or higher), or an AE considered clinically significant during participation in CLIN-1601-101 (NCT04176991). 2. Subjects who are confirmed as compound heterozygous (GAA repeat expansion on only one allele) for Friedreich's ataxia. 3. Subject use of investigational drug (other than CTI-1601) or device within 90 days prior to screening. 4. Subject requires use of amiodarone. 5. Subject used erythropoietin, etravirine, or gamma interferon within 3 months prior to screening. 6. 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. 7. 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. 8. Male subject who has a QT interval corrected for heart rate using Fridericia's formula (QTcF) \> 450 milliseconds or female subject who has a QTcF \> 470 milliseconds on an ECG. 9. Subject has a screening echocardiogram left ventricular ejection fraction \< 45 percent. 10. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants with Treatment Emergent Adverse Events | Through study completion, an average of 75 days | Overall summary of Participants with Treatment Emergent Adverse Events |
| Number of Participants with Treatment Emergent Adverse Events by System Organ Classification and Preferred Term | Through study completion, an average of 75 days | Overall summary of Participants with Treatment Emergent Adverse Events by System Organ Classification (MedDRA version 23.0) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics - Area under the concentration time curve (AUC) from time 0 through the last measurable time point | At baseline and up to 15 days | Summary assessment of changes in the AUC from time 0 to the last measurable time point and during the dosing interval |
| Pharmacokinetics - Terminal half-life estimation | At baseline and up to 15 days | Summary assessment of changes in the terminal half-life estimation |
| Changes from Baseline in Frataxin Levels in Buccal Cell | At baseline and up to 43 days | Summary assessment of changes in frataxin levels in buccal cells |
| Changes from Baseline in Levels of Protein Markers in Buccal Cell | At baseline and up to 43 days | Summary assessment of changes in levels of protein markers in buccal cells |
| Changes from Baseline in Gene Expression in Buccal Cells | At baseline and up to 43 days | Summary assessment of changes in gene expression in buccal cells |
| Pharmacokinetics - Maximum observed plasma concentration after multiple doses | At baseline and up to 15 days | Summary assessment of changes in the maximum observed plasma concentration after multiple doses |
| Changes from Baseline in Gene Expression in Whole Blood | At baseline and up to 16 days | Summary assessment of changes in gene expression in whole blood |
| Changes from Baseline in Frataxin Levels in Skin Punch Cells | At baseline and up to 13 days | Summary assessment of changes in frataxin levels in skin punch cells |
| Changes from Baseline in Levels of Defined Protein Markers in Blood | At baseline and up to 16 days | Summary assessment of changes in levels of defined protein markers in blood |
| Changes from Baseline in Levels of Specialized Lipids in Blood | At baseline and up to 16 days | Summary assessment of changes in levels of specialized lipids in blood |
| Changes from Baseline in Frataxin Levels in Platelets | At baseline and up to 13 days | Summary assessment of changes in frataxin levels in platelets |
| Pharmacokinetics - Minimum or trough plasma concentration after multiple doses | At baseline and up to 15 days | Summary assessment of minimum or trough observed plasma concentration after multiple doses just prior to the administration of a subsequent dose |
Countries
United States
Outcome results
None listed