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

• ClinicalTrials.gov Identifier: NCT04519567
• Recruitment Status: Completed
• First Posted: August 19, 2020
• Last Update Posted: June 30, 2021
• Sponsor: Larimar Therapeutics, Inc.
• Collaborators: Veristat, Inc.; Metrum Research Group, LLC
• Information provided by (Responsible Party): Larimar Therapeutics, Inc.

Tracking Information

• First Submitted Date: August 17, 2020
• First Posted Date: August 19, 2020
• Last Update Posted Date: June 30, 2021
• Actual Study Start Date: July 31, 2020
• Actual Primary Completion Date: March 16, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 17, 2020)

• Number of Participants with Treatment Emergent Adverse Events [ Time Frame: 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 [ Time Frame: 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)

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 17, 2020)

• Pharmacokinetics - Maximum observed plasma concentration after multiple doses [ Time Frame: At baseline and up to 15 days ]
  Summary assessment of changes in the maximum observed plasma concentration after multiple doses
• Pharmacokinetics - Minimum or "trough" plasma concentration after multiple doses [ Time Frame: 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 [ Time Frame: 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
• Pharmacokinetics - Terminal half-life estimation [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: At baseline and up to 43 days ]
  Summary assessment of changes in levels of protein markers in buccal cells
• Changes from Baseline in Gene Expression in Buccal Cells [ Time Frame: At baseline and up to 43 days ]
  Summary assessment of changes in gene expression in buccal cells
• Changes from Baseline in Frataxin Levels in Platelets [ Time Frame: 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 [ Time Frame: At baseline and up to 16 days ]
  Summary assessment of changes in gene expression in whole blood
• Changes from Baseline in Frataxin Levels in Skin Punch Cells [ Time Frame: At baseline and up to 13 days ]
  Summary assessment of changes in frataxin levels in skin punch cells
• Changes from Baseline in Levels of Defined Protein Markers in Blood [ Time Frame: 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 [ Time Frame: At baseline and up to 16 days ]
  Summary assessment of changes in levels of specialized lipids in blood

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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 Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Friedreich Ataxia

Intervention

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

Study Arms

• Experimental: CTI-1601
  Intervention: Biological: CTI-1601
• Placebo Comparator: Placebo
  Intervention: Biological: Placebo

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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 13, 2021): 27
• Original Estimated Enrollment (submitted: August 17, 2020): 30
• Actual Study Completion Date: March 16, 2021
• Actual Primary Completion Date: March 16, 2021 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04519567
• Other Study ID Numbers: CLIN-1601-102
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Larimar Therapeutics, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Larimar Therapeutics, Inc.
• Original Study Sponsor: Same as current

Collaborators

• Veristat, Inc.
• Metrum Research Group, LLC

Investigators

• Principal Investigator: Magdy Shenouda, M.D.; Clinilabs, Inc.

• PRS Account: Larimar Therapeutics, Inc.
• Verification Date: June 2021