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

A Phase 1 Single Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Subcutaneous CTI-1601 Versus Placebo in Subjects With Friedreich's Ataxia

To evaluate the safety and tolerability of single ascending doses of CTI-1601 in participants with Friedreich's ataxia

Study Overview

• Status: Completed
• Conditions: Friedreich Ataxia
• Intervention / Treatment: Biological: CTI-1601; Biological: Placebo

Detailed Description

Single Ascending Dose (SAD), Double-Blind, Placebo Controlled Study.

To evaluate the safety and tolerability of single ascending doses of CTI-1601 in subjects with Friedreich's ataxia.

Secondary Objectives:

1. To evaluate the pharmacokinetics (PK) of CTI-1601 following increasing single doses of subcutaneously (SC) administered CTI-1601.
2. To evaluate the pharmacodynamics (PD) of CTI-1601 following increasing single doses of SC administered CTI-1601.

CTI-1601 or Placebo - Dose/Mode of Administration: Single Dose/Subcutaneous

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Eatontown, New Jersey, United States, 07724
      • Clinilabs Drug Development Corporation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subject has genetically confirmed Friedreich's ataxia diagnosis, 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 minimal assistance if, in the opinion of the 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 are confirmed as compound heterozygous (GAA repeat expansion on only one allele) for Friedreich's ataxia.
2. Subject requires use of amiodarone.
3. Subject used erythropoietin, etravirine, or gamma interferon within 3 months prior to screening.
4. Subject use of investigational drug (other than CTI-1601) or device within 90 days prior to screening.
5. 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.
6. 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.
7. Male subject who has an ECG QTcF > 450 milliseconds or female subject who has an ECG QTcF > 470 milliseconds.
8. Subject has a screening echocardiogram ejection fraction <45 percent.
9. 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.
10. Subjects with known or suspected chronic use of cannabinoid products.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Biological: Placebo; Placebo Comparator
Experimental: CTI-1601	Biological: CTI-1601; CTI-1601 is a recombinant fusion protein and is intended to deliver human frataxin, the protein deficient in Friedreich's ataxia

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Treatment-Emergent Adverse Events	Overall summary of the Participants with Treatment Emergent Adverse Events	Through study completion, an average of 70 days
Number of 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 22.0)	Through study completion, an average of 70 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics - Area under the concentration-time curve after a single dose	Summary assessment of changes in the area under the concentration-time curve after a single dose	Up to 48 hours
Pharmacokinetics - Maximum observed plasma concentration after a single dose	Summary assessment of changes in the maximum observed plasma concentration after a single dose	Up to 48 hours
Pharmacokinetics - Time to reach maximum plasma concentration after a single dose	Summary assessment of changes in time to reach maximum plasma concentration after a single dose	Up to 48 hours
Pharmacokinetics - Area under the concentration-time curve from time 0 to infinity	Summary assessment of changes in the area under the concentration-time curve from time 0 to infinity	48 hours
Pharmacokinetics - Area under the concentration-time curve from time 0 to the last measurable time point	Summary assessment of changes in the Area under the concentration-time curve from time 0 to the last measurable time point	48 hours
Pharmacokinetics - Apparent total plasma clearance	Summary assessment of changes in the apparent total plasma clearance	48 hours
Pharmacokinetics - Terminal half-life estimation	Summary assessment of changes in the terminal half-life estimation	48 hours
Pharmacokinetics - Apparent volume of distribution	Summary assessment of changes in the apparent volume of distribution	48 hours
Changes from Baseline in Frataxin Levels in Buccal Cells	Summary assessment of changes in frataxin levels in buccal cells	At baseline and up to 10 days
Changes from Baseline in Frataxin Levels in Whole Blood	Summary assessment of changes in frataxin levels in whole blood	At baseline and up to 10 days
Changes in Gene Expression Profiling	Summary assessment of changes in gene expression levels	At baseline and up to 10 days

Collaborators and Investigators

• Sponsor: Larimar Therapeutics, Inc.
• Collaborators: Veristat, Inc.; Metrum Research Group, LLC

Publications and helpful links

General Publications

• Koeppen AH. Friedreich's ataxia: pathology, pathogenesis, and molecular genetics. J Neurol Sci. 2011 Apr 15;303(1-2):1-12. doi: 10.1016/j.jns.2011.01.010.
• Delatycki MB, Corben LA. Clinical features of Friedreich ataxia. J Child Neurol. 2012 Sep;27(9):1133-7. doi: 10.1177/0883073812448230. Epub 2012 Jun 29.
• Goodkin DE, Hertsgaard D, Seminary J. Upper extremity function in multiple sclerosis: improving assessment sensitivity with box-and-block and nine-hole peg tests. Arch Phys Med Rehabil. 1988 Oct;69(10):850-4.
• Rudick R, Antel J, Confavreux C, Cutter G, Ellison G, Fischer J, Lublin F, Miller A, Petkau J, Rao S, Reingold S, Syndulko K, Thompson A, Wallenberg J, Weinshenker B, Willoughby E. Clinical outcomes assessment in multiple sclerosis. Ann Neurol. 1996 Sep;40(3):469-79. doi: 10.1002/ana.410400321.
• 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.

Helpful Links

• Friedreich's Ataxia Research Alliance

Study record dates

Study Major Dates

• Study Start (Actual): December 11, 2019
• Primary Completion (Actual): October 31, 2020
• Study Completion (Actual): October 31, 2020

Study Registration Dates

• First Submitted: November 14, 2019
• First Submitted That Met QC Criteria: November 22, 2019
• First Posted (Actual): November 26, 2019

Study Record Updates

• Last Update Posted (Actual): November 12, 2020
• Last Update Submitted That Met QC Criteria: November 9, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Genetic Diseases, Inborn; Neurodegenerative Diseases; Dyskinesias; Spinal Cord Diseases; Heredodegenerative Disorders, Nervous System; Mitochondrial Diseases; Cerebellar Diseases; Spinocerebellar Degenerations; Ataxia; Cerebellar Ataxia; Friedreich Ataxia
• Other Study ID Numbers: CLIN-1601-101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No