A Study to Assess Nomlabofusp in Adolescents and Children With Friedreich's Ataxia

A Phase 1 Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Subcutaneous Nomlabofusp in Adolescents and Children With Friedreich's Ataxia

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).

Study Overview

• Status: Terminated
• Conditions: Friedreich Ataxia
• Intervention / Treatment: Drug: Nomlabofusp; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Chevy Chase, Maryland, United States, 20815
      • Uncommon Cures

Participation Criteria

Eligibility Criteria

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

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nomlabofusp; Subcutaneous injection of 0.8 mg/kg, with a maximum dose of 50 mg, once daily for 7 days	Drug: Nomlabofusp; 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.; Other Names: CTI-1601
Placebo Comparator: Placebo; Subcutaneous injection once daily for 7 days	Drug: Placebo; The placebo is a sterile, preservative-free, clear liquid for subcutaneous injection.; Other Names: CTI-1601 Placebo, Nomlabofusp Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of AEs, TEAEs, related TEAEs, Grade 3/4 TEAEs, and SAEs	Number	Up to 72 days (including screening)
Number of subjects with ISRs	Number	Up to 37 days
Change from baseline in electrocardiogram (ECG) parameter - heart rate (HR)	Number	Baseline, Day 7
Change from baseline in electrocardiogram (ECG) parameter - PR interval	Number	Baseline, Day 7
Change from baseline in electrocardiogram (ECG) parameter - QRS complex	Number	Baseline, Day 7
Change from baseline in electrocardiogram (ECG) parameter - QT interval	Number	Baseline, Day 7
Change from baseline in electrocardiogram (ECG) parameter - QTcF (Corrected QT Interval)	Number	Baseline, Day 7
Change from baseline in echocardiogram (ECHO) parameter - ejection fraction (EF)	Number	Baseline, Day 7
Change from baseline in echocardiogram (ECHO) parameter - left ventricular end-diastolic volume (LV EDV)	Number	Baseline, Day 7
Change from baseline in echocardiogram (ECHO) parameter - left ventricular end-systolic volume (LV ESV)	Number	Baseline, Day 7
Change from baseline in echocardiogram (ECHO) parameter - relative wall thickness (RWT)	Number	Baseline, Day 7
Change from baseline in echocardiogram (ECHO) parameter - left ventricular mass (LVM)	Number	Baseline, Day 7
Change from baseline in echocardiogram (ECHO) parameter - left ventricular posterior wall thickness	Number	Baseline, Day 7
Change from baseline in echocardiogram (ECHO) parameter - septal wall thickness	Number	Baseline, Day 7
Change from baseline in echocardiogram (ECHO) parameter - mitral valve inflow Doppler	Number	Baseline, Day 7
Change from baseline in echocardiogram (ECHO) parameter - tissue Doppler	Number	Baseline, Day 7
Change from baseline in clinical laboratory assessment - sodium	Number	Baseline, Day 7
Change from baseline in clinical laboratory assessment - potassium	Number	Baseline, Day 7
Change from baseline in clinical laboratory assessment - glucose	Number	Baseline, Day 7
Change from baseline in clinical laboratory assessment - blood urea nitrogen	Number	Baseline, Day 7
Change from baseline in clinical laboratory assessment - creatinine	Number	Baseline, Day 7
Change from baseline in clinical laboratory assessment - calcium, chloride	Number	Baseline, Day 7
Change from baseline in clinical laboratory assessment - phosphorus	Number	Baseline, Day 7
Change from baseline in clinical laboratory assessment - total protein	Number	Baseline, Day 7
Change from baseline in clinical laboratory assessment - total CO2	Number	Baseline, Day 7
Change from baseline in clinical laboratory assessment - albumin	Number	Baseline, Day 7
Change from baseline in clinical laboratory assessment - AST	Number	Baseline, Day 7
Change from baseline in clinical laboratory assessment - ALT	Number	Baseline, Day 7
Change from baseline in clinical laboratory assessment - GGT	Number	Baseline, Day 7
Change from baseline in clinical laboratory assessment - ALP	Number	Baseline, Day 7
Change from baseline in clinical laboratory assessment - total bilirubin	Number	Baseline, Day 7
Change from baseline in clinical laboratory assessment - uric acid	Number	Baseline, Day 7
Change from baseline in clinical laboratory assessment - HbA1c	Number	Baseline, Day 7
Change from baseline in clinical laboratory assessment - hemoglobin	Number	Baseline, Day 7
Change from baseline in clinical laboratory assessment - hematocrit	Number	Baseline, Day 7
Change from baseline in clinical laboratory assessment - RBC count	Number	Baseline, Day 7
Change from baseline in clinical laboratory assessment - RDW	Number	Baseline, Day 7
Change from baseline in clinical laboratory assessment - MCV	Number	Baseline, Day 7
Change from baseline in clinical laboratory assessment - MCH	Number	Baseline, Day 7
Change from baseline in clinical laboratory assessment - platelet count	Number	Baseline, Day 7
Change from baseline in clinical laboratory assessment - WBC count	Number	Baseline, Day 7
Change from baseline in clinical laboratory assessment - ANC	Number	Baseline, Day 7
Change from baseline in clinical laboratory assessment - Eosinophils	Number	Baseline, Day 7
Change from baseline in clinical laboratory assessment - Monocytes	Number	Baseline, Day 7
Change from baseline in clinical laboratory assessment - Basophils	Number	Baseline, Day 7
Change from baseline in clinical laboratory assessment - Lymphocytes	Number	Baseline, Day 7
Change from baseline in clinical laboratory assessment - Bands	Number	Baseline, Day 7
Change from baseline in clinical laboratory assessment - Neutrophils	Number	Baseline, Day 7
Change from baseline in clinical laboratory assessment - Cholesterol	Number	Baseline, Day 7
Change from baseline in clinical laboratory assessment - HDL cholesterol	Number	Baseline, Day 7
Change from baseline in clinical laboratory assessment - LDL cholesterol	Number	Baseline, Day 7
Change from baseline in clinical laboratory assessment - Triglycerides	Number	Baseline, Day 7
Change from baseline in clinical laboratory assessment - very low-density lipoprotein cholesterol	Number	Baseline, Day 7
Change from baseline in clinical laboratory assessment - pH	Number	Baseline, Day 7
Change from baseline in clinical laboratory assessment - protein	Number	Baseline, Day 7
Change from baseline in clinical laboratory assessment - blood	Number	Baseline, Day 7
Change from baseline in clinical laboratory assessment - ketones	Number	Baseline, Day 7
Change from baseline in clinical laboratory assessment - bilirubin	Number	Baseline, Day 7
Change from baseline in clinical laboratory assessment - urobilinogen	Number	Baseline, Day 7
Change from baseline in clinical laboratory assessment - nitrites	Number	Baseline, Day 7
Change from baseline in clinical laboratory assessment - leukocyte esterase	Number	Baseline, Day 7
Change from baseline in clinical laboratory assessment - color	Number	Baseline, Day 7
Change from baseline in clinical laboratory assessment - specific gravity	Number	Baseline, Day 7
Change from baseline in pulse rate	Number	Baseline, Day 7
Number of subjects with abnormal physical examinations	Number	Up to 72 days (including screening)
Number of subjects with suicidal ideation, suicidal behavior, and suicidal ideation or behavior based on the Columbia Suicide Severity Rating Scale (C-SSRS)	Number	Up to 72 days (including screening)
Number of subjects who discontinue treatment and/or study	Number	Up to 37 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC0-last	Area under the concentration-time-curve to the last quantifiable timepoint	Days 1, 7
Cmax	Maximum observed concentration	Days 1, 7
Tmax	Time of maximum observed concentration	Days 1, 7
Ctrough	Predose concentration	Days 1, 7
Change from baseline in FXN concentrations normalized to total protein observed in buccal cells collected from cheek swabs	Number	Baseline, Day 7

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.
• Indelicato E, Nachbauer W, Eigentler A, Amprosi M, Matteucci Gothe R, Giunti P, Mariotti C, Arpa J, Durr A, Klopstock T, Schols L, Giordano I, Burk K, Pandolfo M, Didszdun C, Schulz JB, Boesch S; EFACTS (European Friedreich's Ataxia Consortium for Translational Studies). Onset features and time to diagnosis in Friedreich's Ataxia. Orphanet J Rare Dis. 2020 Aug 3;15(1):198. doi: 10.1186/s13023-020-01475-9.
• Lawerman TF, Brandsma R, Burger H, Burgerhof JGM, Sival DA; the Childhood Ataxia and Cerebellar Group of the European Pediatric Neurology Society. Age-related reference values for the pediatric Scale for Assessment and Rating of Ataxia: a multicentre study. Dev Med Child Neurol. 2017 Oct;59(10):1077-1082. doi: 10.1111/dmcn.13507. Epub 2017 Aug 17.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): December 6, 2024
• Primary Completion (Actual): April 28, 2025
• Study Completion (Actual): April 28, 2025

Study Registration Dates

• First Submitted: November 6, 2024
• First Submitted That Met QC Criteria: November 7, 2024
• First Posted (Actual): November 8, 2024

Study Record Updates

• Last Update Posted (Actual): January 28, 2026
• Last Update Submitted That Met QC Criteria: January 26, 2026
• Last Verified: January 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-1601-103

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
• product manufactured in and exported from the U.S.: No