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Review of Cohort 1 data facilitated direct enrollment into open label study and eliminate pause in study drug administration between PK study and open label study.
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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).
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Nomlabofusp | Experimental | Subcutaneous injection of 0.8 mg/kg, with a maximum dose of 50 mg, once daily for 7 days |
|
| Placebo | Placebo Comparator | Subcutaneous injection once daily for 7 days |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Nomlabofusp | Drug | 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. |
| 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) |
| Measure | Description | Time Frame |
|---|---|---|
| AUC0-last | Area under the concentration-time-curve to the last quantifiable timepoint | Days 1, 7 |
| Cmax | Maximum observed concentration |
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Inclusion Criteria:
Subject has genetically confirmed diagnosis of FRDA manifested by homozygous GAA repeat expansions, with repeat sizing (if available) included on the diagnosis report.
Male or female subjects ≥ 2 to < 18 years of age at screening.
Subjects must weigh ≥ 10.0 kg.
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:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Larimar Therapeutics, Inc. | Larimar Therapeutics, Inc. | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Uncommon Cures | Chevy Chase | Maryland | 20815 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22752493 | Background | 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. | |
| 20675166 | Background | 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. |
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| ID | Term |
|---|---|
| D005621 | Friedreich Ataxia |
| ID | Term |
|---|---|
| D013132 | Spinocerebellar Degenerations |
| D002526 | Cerebellar Diseases |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
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|
| Placebo | Drug | The placebo is a sterile, preservative-free, clear liquid for subcutaneous injection. |
|
|
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 |
| 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 |
| 17056635 | Background | 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. |
| 3178453 | Background | 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. |
| 32746884 | Background | 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. |
| 21315377 | Background | 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. |
| 28815574 | Background | 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. |
| 26339677 | Background | 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. |
| 18852343 | Background | Pandolfo M. Friedreich ataxia. Arch Neurol. 2008 Oct;65(10):1296-303. doi: 10.1001/archneur.65.10.1296. |
| 8797541 | Background | 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. |
| D009422 | Nervous System Diseases |
| D013118 | Spinal Cord Diseases |
| D020271 | Heredodegenerative Disorders, Nervous System |
| D019636 | Neurodegenerative Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D028361 | Mitochondrial Diseases |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |