Friedreich Ataxia
Conditions
Brief summary
The goal of this clinical trial is to evaluate the safety and tolerability of nomlabofusp (CTI-1601) in adolescents and children with Friedreich's ataxia (FRDA).
Detailed description
This is a randomized, double-blind, placebo-controlled study evaluating a weight-based dose of nomlabofusp versus placebo in adolescents and children with FRDA. The study will consist of at least two cohorts with at least 12 to 15 participants in each cohort. Participants will be dosed once daily (QD) for 7 days.
Interventions
DRUGNomlabofusp
Nomlabofusp is a recombinant fusion protein provided in a sterile, preservative-free buffered solution for subcutaneous injection intended to deliver human frataxin, the protein deficient in Friedreich's ataxia.
DRUGPlacebo
The placebo is a sterile, preservative-free, clear liquid for subcutaneous injection.
Sponsors
Larimar Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
2 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
1. Subject has genetically confirmed diagnosis of FRDA manifested by homozygous GAA repeat expansions, with repeat sizing (if available) included on the diagnosis report. 2. Male or female subjects ≥ 2 to \< 18 years of age at screening. 3. Subjects must weigh ≥ 10.0 kg. 4. Subject must be able to traverse a distance of 25 feet with or without some assistive device (e.g., cane, walker, crutches, self-propelled wheelchair) and meet the following requirements: 1. Be able to sit upright with thighs together and arms crossed without requiring support on more than 2 sides; 2. Be able to transfer from bed to chair independently or with assistance if, in the opinion of the investigator, the degree of physical disability does not result in undue risk to the subject while participating in the study; and 3. Perform basic age-appropriate daily care, such as feeding themselves and personal hygiene, with minimal assistance.
Exclusion criteria
1. Subjects who are confirmed as compound heterozygous (GAA repeat expansion on only 1 allele) for FRDA. 2. Subject has any condition, disease, or situation, including a cardiac condition or disease, that in the opinion of the investigator could confound the results of the study or put the subject at undue risk, making participation inadvisable. 3. Subjects currently receiving or having received omaveloxolone within 30 days prior to Screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of AEs, TEAEs, related TEAEs, Grade 3/4 TEAEs, and SAEs | Up to 72 days (including screening) | Number |
| Number of subjects with ISRs | Up to 37 days | Number |
| Change from baseline in electrocardiogram (ECG) parameter - heart rate (HR) | Baseline, Day 7 | Number |
| Change from baseline in electrocardiogram (ECG) parameter - PR interval | Baseline, Day 7 | Number |
| Change from baseline in electrocardiogram (ECG) parameter - QRS complex | Baseline, Day 7 | Number |
| Change from baseline in electrocardiogram (ECG) parameter - QT interval | Baseline, Day 7 | Number |
| Change from baseline in electrocardiogram (ECG) parameter - QTcF (Corrected QT Interval) | Baseline, Day 7 | Number |
| Change from baseline in echocardiogram (ECHO) parameter - ejection fraction (EF) | Baseline, Day 7 | Number |
| Change from baseline in echocardiogram (ECHO) parameter - left ventricular end-diastolic volume (LV EDV) | Baseline, Day 7 | Number |
| Change from baseline in echocardiogram (ECHO) parameter - left ventricular end-systolic volume (LV ESV) | Baseline, Day 7 | Number |
| Change from baseline in echocardiogram (ECHO) parameter - relative wall thickness (RWT) | Baseline, Day 7 | Number |
| Change from baseline in echocardiogram (ECHO) parameter - left ventricular mass (LVM) | Baseline, Day 7 | Number |
| Change from baseline in echocardiogram (ECHO) parameter - left ventricular posterior wall thickness | Baseline, Day 7 | Number |
| Change from baseline in echocardiogram (ECHO) parameter - septal wall thickness | Baseline, Day 7 | Number |
| Change from baseline in echocardiogram (ECHO) parameter - mitral valve inflow Doppler | Baseline, Day 7 | Number |
| Change from baseline in echocardiogram (ECHO) parameter - tissue Doppler | Baseline, Day 7 | Number |
| Change from baseline in clinical laboratory assessment - sodium | Baseline, Day 7 | Number |
| Change from baseline in clinical laboratory assessment - potassium | Baseline, Day 7 | Number |
| Change from baseline in clinical laboratory assessment - glucose | Baseline, Day 7 | Number |
| Change from baseline in clinical laboratory assessment - blood urea nitrogen | Baseline, Day 7 | Number |
| Change from baseline in clinical laboratory assessment - creatinine | Baseline, Day 7 | Number |
| Change from baseline in clinical laboratory assessment - calcium, chloride | Baseline, Day 7 | Number |
| Change from baseline in clinical laboratory assessment - phosphorus | Baseline, Day 7 | Number |
| Change from baseline in clinical laboratory assessment - total protein | Baseline, Day 7 | Number |
| Change from baseline in clinical laboratory assessment - total CO2 | Baseline, Day 7 | Number |
| Change from baseline in clinical laboratory assessment - albumin | Baseline, Day 7 | Number |
| Change from baseline in clinical laboratory assessment - AST | Baseline, Day 7 | Number |
| Change from baseline in clinical laboratory assessment - ALT | Baseline, Day 7 | Number |
| Change from baseline in clinical laboratory assessment - GGT | Baseline, Day 7 | Number |
| Change from baseline in clinical laboratory assessment - ALP | Baseline, Day 7 | Number |
| Change from baseline in clinical laboratory assessment - total bilirubin | Baseline, Day 7 | Number |
| Change from baseline in clinical laboratory assessment - uric acid | Baseline, Day 7 | Number |
| Change from baseline in clinical laboratory assessment - HbA1c | Baseline, Day 7 | Number |
| Change from baseline in clinical laboratory assessment - hemoglobin | Baseline, Day 7 | Number |
| Change from baseline in clinical laboratory assessment - hematocrit | Baseline, Day 7 | Number |
| Change from baseline in clinical laboratory assessment - RBC count | Baseline, Day 7 | Number |
| Change from baseline in clinical laboratory assessment - RDW | Baseline, Day 7 | Number |
| Change from baseline in clinical laboratory assessment - MCV | Baseline, Day 7 | Number |
| Change from baseline in clinical laboratory assessment - MCH | Baseline, Day 7 | Number |
| Change from baseline in clinical laboratory assessment - platelet count | Baseline, Day 7 | Number |
| Change from baseline in clinical laboratory assessment - WBC count | Baseline, Day 7 | Number |
| Change from baseline in clinical laboratory assessment - ANC | Baseline, Day 7 | Number |
| Change from baseline in clinical laboratory assessment - Eosinophils | Baseline, Day 7 | Number |
| Change from baseline in clinical laboratory assessment - Monocytes | Baseline, Day 7 | Number |
| Change from baseline in clinical laboratory assessment - Basophils | Baseline, Day 7 | Number |
| Change from baseline in clinical laboratory assessment - Lymphocytes | Baseline, Day 7 | Number |
| Change from baseline in clinical laboratory assessment - Bands | Baseline, Day 7 | Number |
| Change from baseline in clinical laboratory assessment - Neutrophils | Baseline, Day 7 | Number |
| Change from baseline in clinical laboratory assessment - Cholesterol | Baseline, Day 7 | Number |
| Change from baseline in clinical laboratory assessment - HDL cholesterol | Baseline, Day 7 | Number |
| Change from baseline in clinical laboratory assessment - LDL cholesterol | Baseline, Day 7 | Number |
| Change from baseline in clinical laboratory assessment - Triglycerides | Baseline, Day 7 | Number |
| Change from baseline in clinical laboratory assessment - very low-density lipoprotein cholesterol | Baseline, Day 7 | Number |
| Change from baseline in clinical laboratory assessment - pH | Baseline, Day 7 | Number |
| Change from baseline in clinical laboratory assessment - protein | Baseline, Day 7 | Number |
| Change from baseline in clinical laboratory assessment - blood | Baseline, Day 7 | Number |
| Change from baseline in clinical laboratory assessment - ketones | Baseline, Day 7 | Number |
| Change from baseline in clinical laboratory assessment - bilirubin | Baseline, Day 7 | Number |
| Change from baseline in clinical laboratory assessment - urobilinogen | Baseline, Day 7 | Number |
| Change from baseline in clinical laboratory assessment - nitrites | Baseline, Day 7 | Number |
| Change from baseline in clinical laboratory assessment - leukocyte esterase | Baseline, Day 7 | Number |
| Change from baseline in clinical laboratory assessment - color | Baseline, Day 7 | Number |
| Change from baseline in clinical laboratory assessment - specific gravity | Baseline, Day 7 | Number |
| Change from baseline in pulse rate | Baseline, Day 7 | Number |
| Number of subjects with abnormal physical examinations | Up to 72 days (including screening) | Number |
| Number of subjects with suicidal ideation, suicidal behavior, and suicidal ideation or behavior based on the Columbia Suicide Severity Rating Scale (C-SSRS) | Up to 72 days (including screening) | Number |
| Number of subjects who discontinue treatment and/or study | Up to 37 days | Number |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AUC0-last | Days 1, 7 | Area under the concentration-time-curve to the last quantifiable timepoint |
| Cmax | Days 1, 7 | Maximum observed concentration |
| Tmax | Days 1, 7 | Time of maximum observed concentration |
| Ctrough | Days 1, 7 | Predose concentration |
| Change from baseline in FXN concentrations normalized to total protein observed in buccal cells collected from cheek swabs | Baseline, Day 7 | Number |
Countries
United States
Contacts
STUDY_CHAIRLarimar Therapeutics, Inc.
Larimar Therapeutics, Inc.
Outcome results
None listed