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

An Open-Label Extension Study to Assess the Long-Term Safety, Efficacy, Pharmacodynamics, Pharmacokinetics, and Tolerability of Subcutaneous CTI-1601 in Subjects With Friedreich's Ataxia

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.

Study Overview

• Status: Recruiting
• Conditions: Friedreich Ataxia
• Intervention / Treatment: Drug: CTI-1601

Detailed Description

An open-label study designed to evaluate the long-term safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and clinical effects of subcutaneous (SC) administration of CTI-1601, also known as nomlabofusp, in subjects with Friedreich's ataxia (FRDA).

The objectives of this study are:

• To evaluate the safety and PK of long-term subcutaneous (SC) administration of CTI-1601 in subjects with FRDA

• To evaluate the PD and clinical effects of long-term subcutaneous (SC) administration of CTI-1601 in subjects with FRDA on:

  • Tissue FXN concentrations
  • Clinical evaluations of FRDA
  • Gene expression and select lipids

• Study Type: Interventional
• Enrollment (Estimated): 85
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Larimar Therapeutics, Inc.; Phone Number: 844-511-9056; Email: info@larimartx.com

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • Recruiting
      • University of California Los Angeles
  • Florida
    • Gainesville, Florida, United States, 32608
      • Active, not recruiting
      • Fixel Institute for Neurological Disease, University of Florida Health
    • Tampa, Florida, United States, 33612
      • Recruiting
      • Morsani Center for Advanced Health Care, University of South Florida Health
      • Contact: Kayla Zayas; Phone Number: 813-974-5909; Email: Kaylazayas@usf.edu
      • Contact: Lucretia Campbell; Phone Number: 813-974-5909; Email: lcampbel@usf.edu
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Recruiting
      • University of Iowa
  • Maryland
    • Chevy Chase, Maryland, United States, 20815
      • Recruiting
      • Uncommon Cures
      • Contact: Rachael Batabyal, MD; Phone Number: 240-858-4938; Email: Rbatabyal@uncommoncures.com
      • Contact: Tam Roshan Lal, MB, ChB; Phone Number: 240-858-4912; Email: troshanlal@uncommoncures.com
  • New Jersey
    • Eatontown, New Jersey, United States, 07724
      • Recruiting
      • Clinilabs Drug Development, Corp.
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Active, not recruiting
      • Ohio State University United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • Children's Hospital of the University of Pennsylvania (CHOP)
      • Contact: David Lynch, MD, PhD; Phone Number: 215-590-2242; Email: lynchd@pennmedicine.upenn.edu
      • Contact: McKenzie Wells, MS; Phone Number: 267-426-9608; Email: wellsm@chop.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Subjects with FRDA who have or have not previously completed participation in a study of CTI-1601 are eligible to participate in this study unless the subject experienced one or more of the following in a previous CTI-1601 study: a) serious adverse event (SAE) related to study drug; b) significant AE, defined as Grade 3 or higher according to the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 (or higher), related to study drug; c) some other event, related to participation in a previous study with CTI-1601, 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); d) Withdraw from participation in a previous study of CTI-1601 for any reason.
• 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.

Exclusion Criteria:

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

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CTI-1601; 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; CTI-1601 is a recombinant fusion protein and is intended to deliver human frataxin, the protein deficient in patients with Friedreich's ataxia; Other Names: Nomlabofusp

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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

Collaborators and Investigators

• Sponsor: Larimar Therapeutics, Inc.
• Investigators: Study Chair: Larimar Therapeutics, Inc., Larimar Therapeutics, 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.
• 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.
• 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.
• 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.
• Pandolfo M. Friedreich ataxia. Arch Neurol. 2008 Oct;65(10):1296-303. doi: 10.1001/archneur.65.10.1296.
• 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.
• Guidelines MSCfCP. Fatigue and multiple sclerosis: evidence-based management strategies for fatigue in multiple sclerosis. 1998.

Study record dates

Study Major Dates

• Study Start (Actual): January 25, 2024
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: February 15, 2024
• First Submitted That Met QC Criteria: June 5, 2024
• First Posted (Actual): June 6, 2024

Study Record Updates

• Last Update Posted (Actual): May 13, 2026
• Last Update Submitted That Met QC Criteria: May 8, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Metabolic Diseases; Neurodegenerative Diseases; Heredodegenerative Disorders, Nervous System; Spinal Cord Diseases; Mitochondrial Diseases; Cerebellar Diseases; Spinocerebellar Degenerations; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Friedreich Ataxia
• Other Study ID Numbers: CLIN-1601-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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