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

Phase 2
Completed
Conditions
Friedreich Ataxia
Interventions
Other: Placebo
Biological: CTI-1601
Registration Number
NCT05579691
Lead Sponsor
Larimar Therapeutics, Inc.
Brief Summary

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).

Detailed Description

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
28
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.
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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.
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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlaceboPlacebo Comparator
CTI-160lCTI-1601CTI-1601 is a recombinant fusion protein and is intended to deliver human frataxin, the protein deficient in Friedreich's ataxia
Primary Outcome Measures
NameTimeMethod
Number of Participants with Treatment Emergent Adverse EventsThrough study completion, an average of 93 days

Overall summary of Participants with Treatment Emergent Adverse Events

Secondary Outcome Measures
NameTimeMethod
Changes from baseline in frataxin levels in buccal cellsAt baseline and up to 58 days

Summary assessment of changes in frataxin levels in buccal cells

Maximum observed plasma concentration (Cmax) of CTI-1601 after multiple dosesAt baseline and up to 29 days

Summary assessment of changes in the maximum observed plasma concentration (Cmax) of CTI-1601 after multiple doses

Time to maximum observed plasma concentration (tmax) of CTI-1601 after multiple dosesAt baseline and up to 29 days

Summary assessment of the time to maximum observed plasma concentration (tmax) of CTI-1601 after multiple doses

Changes from baseline in frataxin levels in skin punch cellsAt baseline and up to 29 days

Summary assessment of changes in frataxin levels in skin punch cells

Time to last observed plasma concentration (tlast) of CTI-1601 after multiple dosesAt baseline and up to 29 days

Summary assessment of the time to last observed plasma concentration (tlast) of CTI-1601 after multiple doses

Area under the concentration time curve (AUC) of CTI-1601 from time 0 through the last measurable time pointAt baseline and up to 29 days

Summary assessment of changes in the AUC of CTI-1601 from time 0 to the last measurable time point and during the dosing interval

Trial Locations

Locations (1)

Clinilabs Drug Development Corporation

🇺🇸

Eatontown, New Jersey, United States

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