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NCT Number: NCT06447025

An Open-Label Study of 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.

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Key information

Conditions

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

Age range

2 year–60 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

University of California Los Angeles, Los Angeles, California, United States

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About this study

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

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

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

Other names: Nomlabofusp

Primary outcomes

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

    Time frame: Up to 24 months

    Number of subjects

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

    Time frame: Up to 24 months

    Number change in ECG parameters

  3. Change from baseline in left ventricular ejection fraction (LVEF)

    Time frame: Up to 24 months

    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.

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

    Time frame: Up to 24 months

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

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

    Time frame: Up to 24 months

    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.

  6. 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

    Time frame: Up to 24 months

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

    Time frame: Up to 24 months

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

    Time frame: Up to 24 months

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

    Time frame: Up to 24 months

    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.

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

    Time frame: Through study completion, up to 24 months

    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.

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

    Time frame: Up to 24 months

    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.

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

    Time frame: Up to 24 months

    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.

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

    Time frame: Up to 24 months

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

    Time frame: Up to 24 months

    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.

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

    Time frame: Up to 24 months

    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.

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

    Time frame: 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

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

    Time frame: 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

  18. Mean maximum observed concentration (Cmax)

    Time frame: 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

  19. Mean time of maximum observed concentration (Tmax)

    Time frame: 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

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

    Time frame: 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 contacts

Contact information is provided by the study sponsor or research team.

Larimar Therapeutics, Inc.

CONTACT

[email protected]

844-511-9056

Sponsors and collaborators

Lead sponsor

Larimar Therapeutics, Inc.

Industry

Registry information

Official study title

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

Important dates

Study start
2024
Primary completion
2027
Study completion
2027
First posted
Jun 6, 2024
Registry last updated
May 13, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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