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

Phase 1

Completed

• Conditions: Friedreich Ataxia
• Interventions: Biological: Placebo; Biological: CTI-1601

• Registration Number: NCT04519567
• Lead Sponsor: Larimar Therapeutics, Inc.

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.

Study Timeline

• Study Start: 2020-07-31
• Study First Submitted: 2020-08-17
• Study First Submitted QC: 2020-08-17
• Study First Posted: 2020-08-19
• Primary Completion: 2021-03-16
• Study Completion: 2021-03-16
• Status Verified: 2021-06
• Last Update Submitted: 2021-06-29
• Last Update Posted: 2021-06-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 27

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).

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	-
CTI-1601	CTI-1601	-

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Changes from Baseline in Frataxin Levels in Platelets	At baseline and up to 13 days	Summary assessment of changes in frataxin levels in platelets
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
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
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
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
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
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
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 Frataxin Levels in Skin Punch Cells	At baseline and up to 13 days	Summary assessment of changes in frataxin levels in skin punch cells

Trial Locations

Locations (1)

Clinilabs Drug Development Corporation; 🇺🇸 Eatontown, New Jersey, United States