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

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

To evaluate the safety and tolerability of multiple 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

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 Type: Interventional
• Enrollment (Actual): 27
• 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 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.

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 Participants with Treatment Emergent Adverse Events	Through study completion, an average of 75 days
Number of Participants with 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 23.0)	Through study completion, an average of 75 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics - Maximum observed plasma concentration after multiple doses	Summary assessment of changes in the maximum observed plasma concentration after multiple doses	At baseline and up to 15 days
Pharmacokinetics - Minimum or "trough" plasma concentration after multiple doses	Summary assessment of minimum or "trough" observed plasma concentration after multiple doses just prior to the administration of a subsequent dose	At baseline and up to 15 days
Pharmacokinetics - Area under the concentration time curve (AUC) from time 0 through the last measurable time point	Summary assessment of changes in the AUC from time 0 to the last measurable time point and during the dosing interval	At baseline and up to 15 days
Pharmacokinetics - Terminal half-life estimation	Summary assessment of changes in the terminal half-life estimation	At baseline and up to 15 days
Changes from Baseline in Frataxin Levels in Buccal Cell	Summary assessment of changes in frataxin levels in buccal cells	At baseline and up to 43 days
Changes from Baseline in Levels of Protein Markers in Buccal Cell	Summary assessment of changes in levels of protein markers in buccal cells	At baseline and up to 43 days
Changes from Baseline in Gene Expression in Buccal Cells	Summary assessment of changes in gene expression in buccal cells	At baseline and up to 43 days
Changes from Baseline in Frataxin Levels in Platelets	Summary assessment of changes in frataxin levels in platelets	At baseline and up to 13 days
Changes from Baseline in Gene Expression in Whole Blood	Summary assessment of changes in gene expression in whole blood	At baseline and up to 16 days
Changes from Baseline in Frataxin Levels in Skin Punch Cells	Summary assessment of changes in frataxin levels in skin punch cells	At baseline and up to 13 days
Changes from Baseline in Levels of Defined Protein Markers in Blood	Summary assessment of changes in levels of defined protein markers in blood	At baseline and up to 16 days
Changes from Baseline in Levels of Specialized Lipids in Blood	Summary assessment of changes in levels of specialized lipids in blood	At baseline and up to 16 days

Collaborators and Investigators

• Sponsor: Larimar Therapeutics, Inc.
• Collaborators: Veristat, Inc.; Metrum Research Group, LLC
• Investigators: Principal Investigator: Magdy Shenouda, M.D., Clinilabs, Inc.

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): July 31, 2020
• Primary Completion (Actual): March 16, 2021
• Study Completion (Actual): March 16, 2021

Study Registration Dates

• First Submitted: August 17, 2020
• First Submitted That Met QC Criteria: August 17, 2020
• First Posted (Actual): August 19, 2020

Study Record Updates

• Last Update Posted (Actual): June 30, 2021
• Last Update Submitted That Met QC Criteria: June 29, 2021
• Last Verified: June 1, 2021

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-1601-102

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No