Clinical trial NCT04519567: Multiple Ascending Dose Study of CTI-1601 Versus Placebo in Subjects With Friedreich's Ataxia
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Friedreich Ataxia
Lead sponsor: Larimar Therapeutics, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Veristat, Inc.
name: Metrum Research Group, LLC
First posted: 2020-08-19
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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).

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.

Primary outcomes:
measure: Number of Participants with Treatment Emergent Adverse Events
timeFrame: Through study completion, an average of 75 days
measure: Number of Participants with Treatment Emergent Adverse Events by System Organ Classification and Preferred Term
timeFrame: Through study completion, an average of 75 days
Secondary outcomes:
measure: Pharmacokinetics - Maximum observed plasma concentration after multiple doses
timeFrame: At baseline and up to 15 days
measure: Pharmacokinetics - Minimum or "trough" plasma concentration after multiple doses
timeFrame: At baseline and up to 15 days
measure: Pharmacokinetics - Area under the concentration time curve (AUC) from time 0 through the last measurable time point
timeFrame: At baseline and up to 15 days
measure: Pharmacokinetics - Terminal half-life estimation
timeFrame: At baseline and up to 15 days
measure: Changes from Baseline in Frataxin Levels in Buccal Cell
timeFrame: At baseline and up to 43 days
measure: Changes from Baseline in Levels of Protein Markers in Buccal Cell
timeFrame: At baseline and up to 43 days
measure: Changes from Baseline in Gene Expression in Buccal Cells
timeFrame: At baseline and up to 43 days
measure: Changes from Baseline in Frataxin Levels in Platelets
timeFrame: At baseline and up to 13 days
measure: Changes from Baseline in Gene Expression in Whole Blood
timeFrame: At baseline and up to 16 days
measure: Changes from Baseline in Frataxin Levels in Skin Punch Cells
timeFrame: At baseline and up to 13 days
measure: Changes from Baseline in Levels of Defined Protein Markers in Blood
timeFrame: At baseline and up to 16 days
measure: Changes from Baseline in Levels of Specialized Lipids in Blood
timeFrame: At baseline and up to 16 days
Other outcomes:
Locations:
city: Eatontown
country: United States
facility: Clinilabs Drug Development Corporation
state: New Jersey
Study officials:
affiliation: Clinilabs, Inc.
name: Magdy Shenouda, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Plasterer HL, Deutsch EC, Belmonte M, Egan E, Lynch DR, Rusche JR. Development of frataxin gene expression measures for the evaluation of experimental treatments in Friedreich's ataxia. PLoS One. 2013 May 17;8(5):e63958. doi: 10.1371/journal.pone.0063958. Print 2013.