A Double-Blind, Placebo-Controlled, Dose Exploration Study of CTI-1601 in Adult Subjects With Friedreich's Ataxia

To evaluate the safety and tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of subcutaneous (SC) administration of CTI-1601 over 28 days in subjects with Friedreich's ataxia (FRDA).

This is a double-blind, placebo-controlled, study evaluating two doses (25 mg and 50 mg) of CTI-1601.

This study will consist of at least 2 cohorts with 12 to 15 subjects participating in each cohort. Subjects will be dosed once daily (QD) for 14 days followed by dosing every other day (QOD) through Day 28.

Eligibility Criteria:
Inclusion Criteria:

1. Subject has a genetically confirmed diagnosis of FRDA manifested by homozygous GAA repeat expansions, with repeat sizing (if available) included on the diagnosis report.
2. Subject is biologically male or female, 18 years of age or older at screening.
3. Subject must have a mFARS score ≥ 20 and be able to traverse a distance of 25 feet with or without some assistive device (e.g., 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 PI, 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. Subject must weigh \> 40.0 kg.

Exclusion Criteria:

Subjects are excluded from the study if any of the following exclusion criteria are met:

1. If the subject previously participated in a study of CTI-1601 (CLIN-1601-101 (NCT04176991) or CLIN-1601-102 (NCT04519567)) the subject may not enroll in this study if they experienced one or more of the following: (a) Serious Adverse Event (SAE) related to study drug; (b) Adverse Event (AE) defined as Grade 3 or higher according to the CTCAE version 5.0 (or higher), related to study drug; (c) some other event that supports the exclusion of the subject from participating in this study as determined by the Sponsor (i.e., an AE considered clinically significant by the Sponsor regardless of whether it met SAE criteria and regardless of CTCAE grade).
2. Subject who is confirmed as compound heterozygous (GAA repeat expansion on only one allele) for FRDA.
3. Subject used an investigational drug or device within 90 days prior to screening.
4. Subject requires use of amiodarone.
5. Subject used erythropoietin, etravirine, or gamma interferon 90 days prior to Screening.
6. Subject use of biotin supplementation that exceeds 30.0 mcg/day, either as part of a multivitamin or as a standalone supplement, within 7 days prior to the first dose of study drug.
7. Subject uses more than 3.0 grams of acetaminophen daily.
8. Subject receives medication that requires SC injection in the abdomen or thigh.
9. Subject received a vaccination within 14 days of administration of the first dose of study drug or is scheduled to receive a vaccination within 14 days after administration of the last dose of study drug. As an exception, influenza and tetanus vaccines must be administered more than 72 hours prior to the first dose of study drug or 72 hours after the administration of the last dose of study drug.
10. Subject has a screening ECHO LVEF \< 45%.
11. Male subject has a QTcF \> 450 milliseconds or female subject has a QTcF \> 470 milliseconds on an ECG.
12. Subject currently receiving or having received omaveloxolone within 30 days prior to Screening.