Single Ascending Dose Study of CTI-1601 Versus Placebo in Subjects With Friedreich's Ataxia

Study Overview
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Brief Summary
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To evaluate the safety and tolerability of single ascending doses of CTI-1601 in participants with Friedreich's ataxia

Detailed Description
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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: To evaluate the pharmacokinetics (PK) of CTI-1601 following increasing single doses of subcutaneously (SC) administered CTI-1601. 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

Official Title
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A Phase 1 Single Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Subcutaneous CTI-1601 Versus Placebo in Subjects With Friedreich's Ataxia

Conditions
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Friedreich Ataxia

Intervention / Treatment
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* Biological: CTI-1601
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject has genetically confirmed Friedreich's ataxia diagnosis, homozygous GAA repeat expansions, with repeat sizing (if available) included on diagnostic report. Subject is male or female, 18 years of age or older at screening. 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. Subjects must weigh > 40 kilograms (kg). Exclusion Criteria: Subjects who are confirmed as compound heterozygous (GAA repeat expansion on only one allele) for Friedreich's ataxia. Subject requires use of amiodarone. Subject used erythropoietin, etravirine, or gamma interferon within 3 months prior to screening. Subject use of investigational drug (other than CTI-1601) or device within 90 days prior to screening. 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. 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. Male subject who has an ECG QTcF > 450 milliseconds or female subject who has an ECG QTcF > 470 milliseconds. Subject has a screening echocardiogram ejection fraction <45 percent. 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. Subjects with known or suspected chronic use of cannabinoid products.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CTI-1601<br> | Biological: CTI-1601<br>* CTI-1601 is a recombinant fusion protein and is intended to deliver human frataxin, the protein deficient in Friedreich's ataxia<br>|
| Placebo Comparator: Placebo<br> | Biological: Placebo<br>* Placebo Comparator<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Treatment-Emergent Adverse Events | Overall summary of the Participants with Treatment Emergent Adverse Events | Through study completion, an average of 70 days | 
| Number of Treatment Emergent Adverse Events by System Organ Classification and Preferred Term | Overall summary of Participants with Treatment Emergent Adverse Events by System Organ Classification (MedDRA version 22.0) | Through study completion, an average of 70 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics - Area under the concentration-time curve after a single dose | Summary assessment of changes in the area under the concentration-time curve after a single dose | Up to 48 hours | 
| Pharmacokinetics - Maximum observed plasma concentration after a single dose | Summary assessment of changes in the maximum observed plasma concentration after a single dose | Up to 48 hours | 
| Pharmacokinetics - Time to reach maximum plasma concentration after a single dose | Summary assessment of changes in time to reach maximum plasma concentration after a single dose | Up to 48 hours | 
| Pharmacokinetics - Area under the concentration-time curve from time 0 to infinity | Summary assessment of changes in the area under the concentration-time curve from time 0 to infinity | 48 hours | 
| Pharmacokinetics - Area under the concentration-time curve from time 0 to the last measurable time point | Summary assessment of changes in the Area under the concentration-time curve from time 0 to the last measurable time point | 48 hours | 
| Pharmacokinetics - Apparent total plasma clearance | Summary assessment of changes in the apparent total plasma clearance | 48 hours | 
| Pharmacokinetics - Terminal half-life estimation | Summary assessment of changes in the terminal half-life estimation | 48 hours | 
| Pharmacokinetics - Apparent volume of distribution | Summary assessment of changes in the apparent volume of distribution | 48 hours | 
| Changes from Baseline in Frataxin Levels in Buccal Cells | Summary assessment of changes in frataxin levels in buccal cells | At baseline and up to 10 days | 
| Changes from Baseline in Frataxin Levels in Whole Blood | Summary assessment of changes in frataxin levels in whole blood | At baseline and up to 10 days | 
| Changes in Gene Expression Profiling | Summary assessment of changes in gene expression levels | At baseline and up to 10 days |