An Open-Label Study of CTI-1601 in Subjects With Friedreich's Ataxia

NCT06447025 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: CLIN-1601-201
• Study Type: interventional
• Target: 85
• Locations: 1 country
• Sites: 8

Brief Summary

An open label study designed to evaluate the safety, PK, PD, and clinical effects of long-term daily administration of CTI-1601 enrolling adolescent and adult patients with FRDA who have participated in a prior clinical study of CTI-1601 as well as children (age 2 years and older), adolescents and adults with FRDA who have not participated in a prior clinical study of CTI-1601.

Conditions

Friedreich Ataxia

Outcome Measures

Primary Outcomes (20)

• Number of subjects with treatment-emergent adverse events (TEAEs) by System Organ Class (SOC), Preferred Term (PT) and Maximum Severity

  Number of subjects

  Up to 24 months

• Change from baseline in electrocardiogram (ECG) parameters including, but not limited to, HR, RR interval, PR interval, QRS duration, QT interval, and QTcF interval

  Number change in ECG parameters

  Up to 24 months

• Change from baseline in left ventricular ejection fraction (LVEF)

  LVEF indicates the percentage of change in LV volume from diastole to systole that measures how well the left ventricle of the heart pumps blood.

  Up to 24 months

• Change from baseline in left ventricular end-diastolic volume (LVEDV)

  LVEDV is the amount of blood, measured in milliliters (mL), in the heart's left ventricle just before the heart contracts.

  Up to 24 months

• Number of subjects with any suicidal ideation or behavior (Categories 1-10) of the Columbia Suicide Severity Rating Scale (C-SSRS)

  The Columbia Suicide Severity Rating Scale (C-SSRS) is a tool used to assess the occurrence, severity, and frequency of suicidal thoughts and behaviors. A higher score on the C-SSRS generally indicate a worse outcome, as they signify a higher level of suicidal ideation or behavior.

  Up to 24 months

• Change from baseline at each collection timepoint in tissue frataxin concentrations normalized to total protein observed in buccal cells collected from cheek swabs and skin cells collected from skin punch biopsies

  Up to 24 months

• Change from baseline in motor function as assessed by 9-hole peg test (9-HPT)

  Up to 24 months

• Change from baseline in motor function as assessed by the timed 25-foot walk test (T25-FW)

  Up to 24 months

• Change from baseline in neurologic function as assessed by the modified Friedreich's Ataxia Rating Scale (mFARS) total score

  The Modified Friedreich's Ataxia Rating Scale (mFARS) is a modified neurologic scale involving direct subject participation and targets specific areas impacted by Friedreich's ataxia (bulbar, upper limb, lower limb, and upright stability), with scores ranging from 0-67 points, with higher scores indicating a greater level of disability.

  Up to 24 months

• Change from baseline in neurologic function as assessed by the upright stability subscale examination of the mFARS

  The Upright Stability Subscale is an assessment of an individual's ability to maintain balance and stability while standing upright. It has a minimum value of 0 and a maximum value of 36. A higher score indicates a better outcome, reflecting greater stability and balance abilities while standing upright.

  Through study completion, up to 24 months

• Change in activities of daily living (ADLs) as assessed by the Friedreich's Ataxia Rating Scale Activities of Daily Living (FARS_ADL)

  The FARS\_ADL, scored 0 to 36, is a subscale of FARS assessing a subject's ability to complete activities of daily living. A higher score indicates a greater level of disability. The FARS\_ADL questionnaire will be performed at the timepoints indicated in protocol.

  Up to 24 months

• Change from baseline in total fatigue score and all the subscale scores as assessed by the Fatigue Impact Scale (MFIS)

  The Modified Fatigue Impact Scale (MFIS) is a revised form of the Fatigue Impact Scale based on items derived from interviews with MS patients concerning how fatigue impacts their lives. This instrument provides an assessment of the effects of fatigue in terms of physical, cognitive, and psychosocial functioning. Participants rate on a 5-point scale, with 0 = 'Never' to 4 = 'Almost always' their agreement with 21 statements. Total score (0-84) and subscales for physical (0-36), cognitive (0-40) and psychosocial functioning (0-8). The 5-item version is scored (0-20). Higher numbers indicate greater fatigue. The MFIS will be performed at the timepoints indicated in protocol.

  Up to 24 months

• Change from baseline in the assessment of disease as assessed by the Functional Staging for Ataxia

  Up to 24 months

• Overall impression of change as assessed by the patient using the Patient Global Impression of Change (PGI-C) Scale

  The Patient Global Impression of Change (PGI-C) reflects a patient's assessment about the efficacy of treatment. PGIC is a 7 point scale depicting a patient's rating of overall improvement. Patients rate their change as "very much improved," "much improved," "minimally improved," "no change," "minimally worse," "much worse," or "very much worse." The PGI-C will be performed at the timepoints indicated in protocol.

  Up to 24 months

• Overall impression of change assessed by a clinician using the Clinical Global Impression of Change (CGI-C)

  The Clinical Global Impression of Change (CGI-C) is an assessment to measure change in clinical status (symptoms and functional ability) of the subject's condition from baseline with study drug. CGI-C scores range from 1 (very much improved) through to 7 (very much worse). The CGI-C will be performed at the timepoints indicated in protocol.

  Up to 24 months

• Area under the concentration-time curve for the dosing interval (AUC0-tau)

  Days 1, 30, 60, 90: pre-dose, 5, 15, 30 minutes after the dose, and 1, 2, 4, 6, 8 hours after the dose; Day 180: pre-dose and 5, 15 minutes after the dose; Days 270, 360, Q3M thereafter: pre-dose; through study completion, up to 24 months

• Area under the concentration-time curve from time 0 to the time of last quantifiable concentration (AUC0-t)

  Days 1, 30, 60, 90: pre-dose, 5, 15, 30 minutes after the dose, and 1, 2, 4, 6, 8 hours after the dose; Day 180: pre-dose and 5, 15 minutes after the dose; Days 270, 360, Q3M thereafter: pre-dose; through study completion, up to 24 months

• Mean maximum observed concentration (Cmax)

  Days 1, 30, 60, 90: pre-dose, 5, 15, 30 minutes after the dose, and 1, 2, 4, 6, 8 hours after the dose; Day 180: pre-dose and 5, 15 minutes after the dose; Days 270, 360, Q3M thereafter: pre-dose; through study completion, up to 24 months

• Mean time of maximum observed concentration (Tmax)

  Days 1, 30, 60, 90: pre-dose, 5, 15, 30 minutes after the dose, and 1, 2, 4, 6, 8 hours after the dose; Day 180: pre-dose and 5, 15 minutes after the dose; Days 270, 360, Q3M thereafter: pre-dose; through study completion, up to 24 months

• Concentration reached immediately before the next dose is administered (Ctrough)

  Days 1, 30, 60, 90: pre-dose, 5, 15, 30 minutes after the dose, and 1, 2, 4, 6, 8 hours after the dose; Day 180: pre-dose and 5, 15 minutes after the dose; Days 270, 360, Q3M thereafter: pre-dose; through study completion, up to 24 months

Study Arms (1)

CTI-1601

EXPERIMENTAL

Once daily subcutaneous injection of 50 mg CTI-1601 in subjects ≥ 18 years of age or a weight-based dose of 0.8 mg/kg up to a maximum of 50 mg in subjects ≥ 2 to 17 years of age.

Drug: CTI-1601

Interventions

CTI-1601 DRUG

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

Also known as: Nomlabofusp

CTI-1601

Eligibility Criteria

• Age: 2 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Subject has a HbA1c less than or equal to 7.0%.
• Subject must demonstrate sufficient dexterity and visual acuity to prepare and self-administer SC injections of CTI-1601 QD or is able to identify a caregiver who will be trained and committed to prepare and administer the daily injections.
• If subject is taking permitted concomitant medication(s), subject must have been on a stable dose and frequency of medication(s) over the past 28 days prior to the initiation of Screening; however, subjects taking niacin and resveratrol must have been on a stable dose and frequency for 90 days prior to the initiation of Screening
• \- Subjects who are currently receiving omaveloxolone or intend to receive omaveloxolone are permitted in the study but must either receive CTI-1601 for 3 months prior to their first dose of omaveloxolone or receive omaveloxolone for 3 months prior to their first dose of CTI-1601.

You may not qualify if:

• Subjects who are confirmed as compound heterozygous (GAA repeat expansion on only one allele) for FRDA.
• Subject has any condition, disease, or situation, including a cardiac condition or disease, that in the opinion of the PI, could confound the results of the study or put the subject at undue risk, making participation inadvisable.
• Subject used any 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 90 days prior to Screening.
• Subject use of biotin supplementation that exceeds 30 mcg/day, either as part of a multivitamin or as a standalone supplement, within 7 days prior to the first dose of study drug. Biotin supplementation ≤30 mcg/day is permitted if taken at a stable dose and frequency for at least 28 days prior to Screening and there is a commitment from the subject to maintain the biotin dose throughout the study (due to interference with assays).
• Subject uses more than 3 grams of acetaminophen daily.
• Subject receives medication that requires SC injection in the abdomen or thigh.
• Subject is unable to discontinue medications that have not been at a stable dose and frequency for at least 28 days prior to Screening.
• Subject has a Screening echocardiogram (ECHO) LVEF \< 45%.
• Male subject has a QTcF \> 450 milliseconds or female subject has a QTcF \> 470 milliseconds on an ECG.

Sponsors & Collaborators

• Larimar Therapeutics, Inc.: lead

Study Sites (8)

University of California Los Angeles

Los Angeles, California, 90095, United States

RECRUITING

Fixel Institute for Neurological Disease, University of Florida Health

Gainesville, Florida, 32608, United States

ACTIVE NOT RECRUITING

Morsani Center for Advanced Health Care, University of South Florida Health

Tampa, Florida, 33612, United States

RECRUITING

University of Iowa

Iowa City, Iowa, 52242, United States

RECRUITING

Uncommon Cures

Chevy Chase, Maryland, 20815, United States

RECRUITING

Clinilabs Drug Development, Corp.

Eatontown, New Jersey, 07724, United States

RECRUITING

Ohio State University United States

Columbus, Ohio, 43210, United States

ACTIVE NOT RECRUITING

Children's Hospital of the University of Pennsylvania (CHOP)

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Related Publications (10)

• 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

• 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.

  PMID: 20675166 BACKGROUND

• Fahey MC, Corben L, Collins V, Churchyard AJ, Delatycki MB. How is disease progress in Friedreich's ataxia best measured? A study of four rating scales. J Neurol Neurosurg Psychiatry. 2007 Apr;78(4):411-3. doi: 10.1136/jnnp.2006.096008. Epub 2006 Oct 20.

  PMID: 17056635 BACKGROUND

• Fisk JD, Ritvo PG, Ross L, Haase DA, Marrie TJ, Schlech WF. Measuring the functional impact of fatigue: initial validation of the fatigue impact scale. Clin Infect Dis. 1994 Jan;18 Suppl 1:S79-83. doi: 10.1093/clinids/18.supplement_1.s79.

  PMID: 8148458 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

• 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

• Guidelines MSCfCP. Fatigue and multiple sclerosis: evidence-based management strategies for fatigue in multiple sclerosis. 1998.

  BACKGROUND

• 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.

  PMID: 26339677 BACKGROUND

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

  PMID: 18852343 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

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

• Larimar Therapeutics, Inc.

  Larimar Therapeutics, Inc.

  STUDY CHAIR

Central Study Contacts

Larimar Therapeutics, Inc.

CONTACT

844-511-9056; info@larimartx.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 15, 2024
• First Posted: June 6, 2024
• Study Start: January 25, 2024
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027
• Last Updated: May 13, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (8)