Multiple 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 multiple ascending doses of CTI-1601 in participants with Friedreich's ataxia

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

Official Title
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A Phase 1 Multiple 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 manifested by 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 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. Subjects must weigh > 40 kilograms (kg). Exclusion Criteria: 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). Subjects who are confirmed as compound heterozygous (GAA repeat expansion on only one allele) for Friedreich's ataxia. Subject use of investigational drug (other than CTI-1601) or device within 90 days prior to screening. Subject requires use of amiodarone. Subject used erythropoietin, etravirine, or gamma interferon within 3 months 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 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. Subject has a screening echocardiogram left ventricular 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.

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 Participants with Treatment Emergent Adverse Events | Through study completion, an average of 75 days | 
| Number of Participants with 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 23.0) | Through study completion, an average of 75 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics - Maximum observed plasma concentration after multiple doses | Summary assessment of changes in the maximum observed plasma concentration after multiple doses | At baseline and up to 15 days | 
| Pharmacokinetics - Minimum or trough plasma concentration after multiple doses | Summary assessment of minimum or trough observed plasma concentration after multiple doses just prior to the administration of a subsequent dose | At baseline and up to 15 days | 
| Pharmacokinetics - Area under the concentration time curve (AUC) from time 0 through the last measurable time point | Summary assessment of changes in the AUC from time 0 to the last measurable time point and during the dosing interval | At baseline and up to 15 days | 
| Pharmacokinetics - Terminal half-life estimation | Summary assessment of changes in the terminal half-life estimation | At baseline and up to 15 days | 
| Changes from Baseline in Frataxin Levels in Buccal Cell | Summary assessment of changes in frataxin levels in buccal cells | At baseline and up to 43 days | 
| Changes from Baseline in Levels of Protein Markers in Buccal Cell | Summary assessment of changes in levels of protein markers in buccal cells | At baseline and up to 43 days | 
| Changes from Baseline in Gene Expression in Buccal Cells | Summary assessment of changes in gene expression in buccal cells | At baseline and up to 43 days | 
| Changes from Baseline in Frataxin Levels in Platelets | Summary assessment of changes in frataxin levels in platelets | At baseline and up to 13 days | 
| Changes from Baseline in Gene Expression in Whole Blood | Summary assessment of changes in gene expression in whole blood | At baseline and up to 16 days | 
| Changes from Baseline in Frataxin Levels in Skin Punch Cells | Summary assessment of changes in frataxin levels in skin punch cells | At baseline and up to 13 days | 
| Changes from Baseline in Levels of Defined Protein Markers in Blood | Summary assessment of changes in levels of defined protein markers in blood | At baseline and up to 16 days | 
| Changes from Baseline in Levels of Specialized Lipids in Blood | Summary assessment of changes in levels of specialized lipids in blood | At baseline and up to 16 days |