Clinical trial NCT06447025: An Open Label Extension Study of CTI-1601 in Subjects With Friedreich's Ataxia
Official title: 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
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: PHASE2
Conditions: Friedreich Ataxia
Lead sponsor: Larimar Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2024-06-06
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is an open-label extension (OLE) 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 OLE study are:

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

Detailed description: This is an open label extension (OLE) study in patients with FRDA who participated in a prior clinical study of CTI-1601 to evaluate the safety, PK, PD, and clinical effects of long-term daily administration of CTI-1601.

Eligibility criteria: Inclusion Criteria:

* Subjects with FRDA who previously completed participation in a study of CTI-1601 will be 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.

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.

Primary outcomes:
measure: Number of subjects with treatment-emergent adverse events (TEAEs) by System Organ Class (SOC), Preferred Term (PT) and Maximum Severity
timeFrame: Up to 24 months
measure: Number of subjects with abnormal laboratory test results
timeFrame: Up to 24 months
measure: Change from baseline in electrocardiogram (ECG) parameters including, but not limited to, HR, RR interval, PR interval, QRS duration, QT interval, and QTcF interval
timeFrame: Up to 24 months
measure: Change from baseline in left ventricular ejection fraction (LVEF)
timeFrame: Up to 24 months
measure: Change from baseline in left ventricular end-diastolic volume (LVEDV)
timeFrame: Up to 24 months
measure: Change from baseline in blood pressure (mmHg)
timeFrame: Up to 24 months
measure: Change from baseline in pulse (bpm)
timeFrame: Up to 24 months
measure: Change from baseline in temperature (°C)
timeFrame: Up to 24 months
measure: Change from baseline in respiration rate (breaths per minute)
timeFrame: Up to 24 months
measure: Number of subjects with any suicidal ideation or behavior (Categories 1-10) of the Columbia Suicide Severity Rating Scale (C-SSRS)
timeFrame: Up to 24 months
measure: 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
timeFrame: Up to 24 months
measure: Change from baseline in motor function as assessed by 9-hole peg test (9-HPT)
timeFrame: Up to 24 months
measure: Change from baseline in motor function as assessed by the timed 25-foot walk test (T25-FW)
timeFrame: Up to 24 months
measure: Change from baseline in neurologic function as assessed by the modified Friedreich's Ataxia Rating Scale (mFARS) total score
timeFrame: Up to 24 months
measure: Change from baseline in neurologic function as assessed by the upright stability subscale examination of the mFARS
timeFrame: Through study completion, up to 24 months
measure: Change in activities of daily living (ADLs) as assessed by the Friedreich's Ataxia Rating Scale Activities of Daily Living (FARS_ADL)
timeFrame: Up to 24 months
measure: Change from baseline in total fatigue score and all the subscale scores as assessed by the Fatigue Impact Scale (MFIS)
timeFrame: Up to 24 months
measure: Change from baseline in the assessment of disease as assessed by the Functional Staging for Ataxia
timeFrame: Up to 24 months
measure: Overall impression of change as assessed by the patient using the Patient Global Impression of Change (PGI-C) Scale
timeFrame: Up to 24 months
measure: Overall impression of change assessed by a clinician using the Clinical Global Impression of Change (CGI-C)
timeFrame: Up to 24 months
measure: Area under the concentration-time curve for the dosing interval (AUC0-tau)
timeFrame: 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
measure: Area under the concentration-time curve from time 0 to the time of last quantifiable concentration (AUC0-t)
timeFrame: 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
measure: Mean maximum observed concentration (Cmax)
timeFrame: 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
measure: Mean time of maximum observed concentration (Tmax)
timeFrame: 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
measure: Concentration reached immediately before the next dose is administered (Ctrough)
timeFrame: 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
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California Los Angeles
state: California
city: Gainesville
country: United States
facility: Fixel Institute for Neurological Disease, University of Florida Health
state: Florida
city: Tampa
country: United States
facility: Morsani Center for Advanced Health Care, University of South Florida Health
state: Florida
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Eatontown
country: United States
facility: Clinilabs Drug Development, Corp.
state: New Jersey
city: Columbus
country: United States
facility: Ohio State University United States
state: Ohio
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: Larimar Therapeutics, Inc.
name: Larimar Therapeutics, Inc.
role: STUDY_CHAIR
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