A Double-Blind, Placebo-Controlled, Dose Exploration Study of CTI-1601 in Adult Subjects With Friedreich's Ataxia

Friedreich Ataxia Clinical Trial

Official title:

A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Dose Exploration Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of Subcutaneous CTI-1601 in Adult Subjects With Friedreich's Ataxia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05579691
• Other study ID #: CLIN-1601-200
• Status: Completed
• Phase: Phase 2
• Start date: September 21, 2022
• Est. completion date: December 4, 2023

Study information

• Verified date: February 2024
• Source: Larimar Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To evaluate the safety and tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of subcutaneous (SC) administration of CTI-1601 over 28 days in subjects with Friedreich's ataxia (FRDA).

Description:

This is a double-blind, placebo-controlled, study evaluating two doses (25 mg and 50 mg) of CTI-1601.

This study will consist of at least 2 cohorts with 12 to 15 subjects participating in each cohort. Subjects will be dosed once daily (QD) for 14 days followed by dosing every other day (QOD) through Day 28.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: December 4, 2023
• Est. primary completion date: December 4, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Subject has a genetically confirmed diagnosis of FRDA manifested by homozygous GAA repeat expansions, with repeat sizing (if available) included on the diagnosis report.

2. Subject is biologically male or female, 18 years of age or older at screening.

3. Subject must have a mFARS score = 20 and be able to traverse a distance of 25 feet with or without some assistive device (e.g., 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 PI, 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. Subject must weigh > 40.0 kg.

Exclusion Criteria:

Subjects are excluded from the study if any of the following exclusion criteria are met:

1. If the subject previously participated in a study of CTI-1601 (CLIN-1601-101 (NCT04176991) or CLIN-1601-102 (NCT04519567)) the subject may not enroll in this study if they experienced one or more of the following: (a) Serious Adverse Event (SAE) related to study drug; (b) Adverse Event (AE) defined as Grade 3 or higher according to the CTCAE version 5.0 (or higher), related to study drug; (c) some other event that supports the exclusion of the subject from participating in this study as determined by the Sponsor (i.e., an AE considered clinically significant by the Sponsor regardless of whether it met SAE criteria and regardless of CTCAE grade).

2. Subject who is confirmed as compound heterozygous (GAA repeat expansion on only one allele) for FRDA.

3. Subject used an investigational drug or device within 90 days prior to screening.

4. Subject requires use of amiodarone.

5. Subject used erythropoietin, etravirine, or gamma interferon 90 days prior to Screening.

6. Subject use of biotin supplementation that exceeds 30.0 mcg/day, either as part of a multivitamin or as a standalone supplement, within 7 days prior to the first dose of study drug.

7. Subject uses more than 3.0 grams of acetaminophen daily.

8. Subject receives medication that requires SC injection in the abdomen or thigh.

9. Subject received a vaccination within 14 days of administration of the first dose of study drug or is scheduled to receive a vaccination within 14 days after administration of the last dose of study drug. As an exception, influenza and tetanus vaccines must be administered more than 72 hours prior to the first dose of study drug or 72 hours after the administration of the last dose of study drug.

10. Subject has a screening ECHO LVEF < 45%.

11. Male subject has a QTcF > 450 milliseconds or female subject has a QTcF > 470 milliseconds on an ECG.

12. Subject currently receiving or having received omaveloxolone within 30 days prior to Screening.

Related Conditions & MeSH terms

• Ataxia
• Cerebellar Ataxia
• 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

Other:
• Placebo
Placebo Comparator

Locations

Country	Name	City	State
United States	Clinilabs Drug Development Corporation	Eatontown	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Larimar Therapeutics, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (9)

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. — View Citation

Deutsch EC, Santani AB, Perlman SL, Farmer JM, Stolle CA, Marusich MF, Lynch DR. A rapid, noninvasive immunoassay for frataxin: utility in assessment of Friedreich ataxia. Mol Genet Metab. 2010 Oct-Nov;101(2-3):238-45. doi: 10.1016/j.ymgme.2010.07.001. Epub 2010 Jul 8. — View Citation

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. — View Citation

Indelicato E, Nachbauer W, Eigentler A, Amprosi M, Matteucci Gothe R, Giunti P, Mariotti C, Arpa J, Durr A, Klopstock T, Schols L, Giordano I, Burk K, Pandolfo M, Didszdun C, Schulz JB, Boesch S; EFACTS (European Friedreich's Ataxia Consortium for Translational Studies). Onset features and time to diagnosis in Friedreich's Ataxia. Orphanet J Rare Dis. 2020 Aug 3;15(1):198. doi: 10.1186/s13023-020-01475-9. — View Citation

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. — View Citation

Lawerman TF, Brandsma R, Burger H, Burgerhof JGM, Sival DA; the Childhood Ataxia and Cerebellar Group of the European Pediatric Neurology Society. Age-related reference values for the pediatric Scale for Assessment and Rating of Ataxia: a multicentre study. Dev Med Child Neurol. 2017 Oct;59(10):1077-1082. doi: 10.1111/dmcn.13507. Epub 2017 Aug 17. — View Citation

Lazaropoulos M, Dong Y, Clark E, Greeley NR, Seyer LA, Brigatti KW, Christie C, Perlman SL, Wilmot GR, Gomez CM, Mathews KD, Yoon G, Zesiewicz T, Hoyle C, Subramony SH, Brocht AF, Farmer JM, Wilson RB, Deutsch EC, Lynch DR. Frataxin levels in peripheral tissue in Friedreich ataxia. Ann Clin Transl Neurol. 2015 Aug;2(8):831-42. doi: 10.1002/acn3.225. Epub 2015 Jul 1. — View Citation

Pandolfo M. Friedreich ataxia. Arch Neurol. 2008 Oct;65(10):1296-303. doi: 10.1001/archneur.65.10.1296. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants with Treatment Emergent Adverse Events	Overall summary of Participants with Treatment Emergent Adverse Events	Through study completion, an average of 93 days
Secondary	Maximum observed plasma concentration (Cmax) of CTI-1601 after multiple doses	Summary assessment of changes in the maximum observed plasma concentration (Cmax) of CTI-1601 after multiple doses	At baseline and up to 29 days
Secondary	Area under the concentration time curve (AUC) of CTI-1601 from time 0 through the last measurable time point	Summary assessment of changes in the AUC of CTI-1601 from time 0 to the last measurable time point and during the dosing interval	At baseline and up to 29 days
Secondary	Time to maximum observed plasma concentration (tmax) of CTI-1601 after multiple doses	Summary assessment of the time to maximum observed plasma concentration (tmax) of CTI-1601 after multiple doses	At baseline and up to 29 days
Secondary	Time to last observed plasma concentration (tlast) of CTI-1601 after multiple doses	Summary assessment of the time to last observed plasma concentration (tlast) of CTI-1601 after multiple doses	At baseline and up to 29 days
Secondary	Changes from baseline in frataxin levels in buccal cells	Summary assessment of changes in frataxin levels in buccal cells	At baseline and up to 58 days
Secondary	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 29 days