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

NCT04519567 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: CLIN-1601-102
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Friedreich Ataxia

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (12)

• Pharmacokinetics - Maximum observed plasma concentration after multiple doses

  At baseline and up to 15 days

• Pharmacokinetics - Minimum or "trough" plasma concentration after multiple doses

  At baseline and up to 15 days

• Pharmacokinetics - Area under the concentration time curve (AUC) from time 0 through the last measurable time point

  At baseline and up to 15 days

• Pharmacokinetics - Terminal half-life estimation

  At baseline and up to 15 days

• Changes from Baseline in Frataxin Levels in Buccal Cell

  At baseline and up to 43 days

Study Arms (2)

CTI-1601

EXPERIMENTAL

Biological: CTI-1601

Placebo

PLACEBO COMPARATOR

Biological: Placebo

Interventions

CTI-1601 BIOLOGICAL

CTI-1601 is a recombinant fusion protein and is intended to deliver human frataxin, the protein deficient in Friedreich's ataxia

CTI-1601

Placebo BIOLOGICAL

Placebo Comparator

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject has genetically confirmed Friedreich's ataxia diagnosis manifested by homozygous GAA repeat expansions, with repeat sizing (if available) included on diagnostic report.
• Subject is male or female, 18 years of age or older at screening
• 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.
• Subjects must weigh \> 40 kilograms (kg).

You may not qualify if:

• 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).
• Subjects who are confirmed as compound heterozygous (GAA repeat expansion on only one allele) for Friedreich's ataxia.
• Subject use of investigational drug (other than CTI-1601) or device within 90 days prior to screening.
• Subject requires use of amiodarone.
• Subject used erythropoietin, etravirine, or gamma interferon within 3 months prior to screening.
• 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.
• 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.
• 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.
• Subject has a screening echocardiogram left ventricular ejection fraction \< 45 percent.
• 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.

Sponsors & Collaborators

• Larimar Therapeutics, Inc.: lead
• Veristat, Inc.: collaborator
• Metrum Research Group, LLC: collaborator

Study Sites (1)

Clinilabs Drug Development Corporation

Eatontown, New Jersey, 07724, United States

Location

Related Publications (5)

• 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.

  PMID: 21315377 BACKGROUND

• 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.

  PMID: 22752493 BACKGROUND

• 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.

  PMID: 3178453 BACKGROUND

• 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.

  PMID: 8797541 BACKGROUND

• 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.

  PMID: 23691127 BACKGROUND

Related Links

• Friedreich's Ataxia Research Alliance

MeSH Terms

Conditions

Friedreich Ataxia

Condition Hierarchy (Ancestors)

Spinocerebellar Degenerations; Cerebellar Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Spinal Cord Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Mitochondrial Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Magdy Shenouda, M.D.

  Clinilabs, Inc.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 17, 2020
• First Posted: August 19, 2020
• Study Start: July 31, 2020
• Primary Completion: March 16, 2021
• Study Completion: March 16, 2021
• Last Updated: June 30, 2021

Record last verified: 2021-06

Locations

US (1)