Multiple Ascending Dose Study of CTI-1601 Versus Placebo in Subjects With Friedreich's Ataxia
Primary Purpose
Friedreich Ataxia
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
CTI-1601
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Friedreich Ataxia
Eligibility Criteria
Inclusion Criteria:
- Subject has genetically confirmed Friedreich's ataxia diagnosis manifested by homozygous GAA repeat expansions, with repeat sizing (if available) included on diagnostic report.
- Subject is male or female, 18 years of age or older at screening
- Subject must have a mFARS_neuro score ≥ 20 and be able to traverse a distance of 25 feet with or without some assistive device (cane, walker, crutches, self-propelled wheelchair) and (a) be able to sit upright with thighs together and arms crossed without requiring support on more than two sides; (b) be able to transfer from bed to chair independently or with assistance if, in the opinion of the principal investigator, the degree of physical disability does not result in undue risk to the subject while participating in the study; and (c) perform basic daily care, such as feeding themselves and personal hygiene, with minimal assistance.
- Subjects must weigh > 40 kilograms (kg).
Exclusion Criteria:
- Subjects who had a serious adverse event (SAE), an adverse event (AE) that is Grade 3 or higher according to the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 (or higher), or an AE considered clinically significant during participation in CLIN-1601-101 (NCT04176991).
- Subjects who are confirmed as compound heterozygous (GAA repeat expansion on only one allele) for Friedreich's ataxia.
- Subject use of 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 3 months prior to screening.
- Subject use of daily biotin supplementation that exceeds 30 mcg/day, either as part of a multivitamin or as a standalone supplement, within 7 days prior to study drug administration and/or throughout the entire study.
- Subject has clinically significant arrhythmia on electrocardiogram (ECG), or evidence of predisposition to significant ventricular arrhythmia on ECG, or evidence of active and unstable coronary artery disease.
- Male subject who has a QT interval corrected for heart rate using Fridericia's formula (QTcF) > 450 milliseconds or female subject who has a QTcF > 470 milliseconds on an ECG.
- Subject has a screening echocardiogram left ventricular ejection fraction < 45 percent.
- Subject has a history of aspiration, aspiration pneumonia, or recurrent episodes of pneumonia (greater than or equal to 2 episodes of pneumonia) within the last 12 months.
Sites / Locations
- Clinilabs Drug Development Corporation
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
CTI-1601
Placebo
Arm Description
Outcomes
Primary Outcome Measures
Number of Participants with Treatment Emergent Adverse Events
Overall summary of Participants with Treatment Emergent Adverse Events
Number of Participants with Treatment Emergent Adverse Events by System Organ Classification and Preferred Term
Overall summary of Participants with Treatment Emergent Adverse Events by System Organ Classification (MedDRA version 23.0)
Secondary Outcome Measures
Pharmacokinetics - Maximum observed plasma concentration after multiple doses
Summary assessment of changes in the maximum observed plasma concentration after multiple doses
Pharmacokinetics - Minimum or "trough" plasma concentration after multiple doses
Summary assessment of minimum or "trough" observed plasma concentration after multiple doses just prior to the administration of a subsequent dose
Pharmacokinetics - Area under the concentration time curve (AUC) from time 0 through the last measurable time point
Summary assessment of changes in the AUC from time 0 to the last measurable time point and during the dosing interval
Pharmacokinetics - Terminal half-life estimation
Summary assessment of changes in the terminal half-life estimation
Changes from Baseline in Frataxin Levels in Buccal Cell
Summary assessment of changes in frataxin levels in buccal cells
Changes from Baseline in Levels of Protein Markers in Buccal Cell
Summary assessment of changes in levels of protein markers in buccal cells
Changes from Baseline in Gene Expression in Buccal Cells
Summary assessment of changes in gene expression in buccal cells
Changes from Baseline in Frataxin Levels in Platelets
Summary assessment of changes in frataxin levels in platelets
Changes from Baseline in Gene Expression in Whole Blood
Summary assessment of changes in gene expression in whole blood
Changes from Baseline in Frataxin Levels in Skin Punch Cells
Summary assessment of changes in frataxin levels in skin punch cells
Changes from Baseline in Levels of Defined Protein Markers in Blood
Summary assessment of changes in levels of defined protein markers in blood
Changes from Baseline in Levels of Specialized Lipids in Blood
Summary assessment of changes in levels of specialized lipids in blood
Full Information
NCT ID
NCT04519567
First Posted
August 17, 2020
Last Updated
June 29, 2021
Sponsor
Larimar Therapeutics, Inc.
Collaborators
Veristat, Inc., Metrum Research Group, LLC
1. Study Identification
Unique Protocol Identification Number
NCT04519567
Brief Title
Multiple Ascending Dose Study of CTI-1601 Versus Placebo in Subjects With Friedreich's Ataxia
Official Title
A Phase 1 Multiple Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Subcutaneous CTI-1601 Versus Placebo in Subjects With Friedreich's Ataxia
Study Type
Interventional
2. Study Status
Record Verification Date
June 2021
Overall Recruitment Status
Completed
Study Start Date
July 31, 2020 (Actual)
Primary Completion Date
March 16, 2021 (Actual)
Study Completion Date
March 16, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Larimar Therapeutics, Inc.
Collaborators
Veristat, Inc., Metrum Research Group, LLC
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
To evaluate the safety and tolerability of multiple ascending doses of CTI-1601 in participants with Friedreich's ataxia
Detailed Description
Multiple Ascending Dose (MAD), Double-Blind, Placebo Controlled Study.
To evaluate the safety and tolerability of multiple ascending doses of CTI-1601 in subjects with Friedreich's ataxia.
Secondary Objectives:
To evaluate the pharmacokinetics (PK) of CTI-1601 following, multiple, increasing, doses of subcutaneously (SC) administered CTI-1601.
To evaluate the pharmacodynamics (PD) of CTI-1601 following, multiple, increasing, doses of SC administered CTI-1601.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Friedreich Ataxia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
27 (Actual)
8. Arms, Groups, and Interventions
Arm Title
CTI-1601
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Biological
Intervention Name(s)
CTI-1601
Intervention Description
CTI-1601 is a recombinant fusion protein and is intended to deliver human frataxin, the protein deficient in Friedreich's ataxia
Intervention Type
Biological
Intervention Name(s)
Placebo
Intervention Description
Placebo Comparator
Primary Outcome Measure Information:
Title
Number of Participants with Treatment Emergent Adverse Events
Description
Overall summary of Participants with Treatment Emergent Adverse Events
Time Frame
Through study completion, an average of 75 days
Title
Number of Participants with Treatment Emergent Adverse Events by System Organ Classification and Preferred Term
Description
Overall summary of Participants with Treatment Emergent Adverse Events by System Organ Classification (MedDRA version 23.0)
Time Frame
Through study completion, an average of 75 days
Secondary Outcome Measure Information:
Title
Pharmacokinetics - Maximum observed plasma concentration after multiple doses
Description
Summary assessment of changes in the maximum observed plasma concentration after multiple doses
Time Frame
At baseline and up to 15 days
Title
Pharmacokinetics - Minimum or "trough" plasma concentration after multiple doses
Description
Summary assessment of minimum or "trough" observed plasma concentration after multiple doses just prior to the administration of a subsequent dose
Time Frame
At baseline and up to 15 days
Title
Pharmacokinetics - Area under the concentration time curve (AUC) from time 0 through the last measurable time point
Description
Summary assessment of changes in the AUC from time 0 to the last measurable time point and during the dosing interval
Time Frame
At baseline and up to 15 days
Title
Pharmacokinetics - Terminal half-life estimation
Description
Summary assessment of changes in the terminal half-life estimation
Time Frame
At baseline and up to 15 days
Title
Changes from Baseline in Frataxin Levels in Buccal Cell
Description
Summary assessment of changes in frataxin levels in buccal cells
Time Frame
At baseline and up to 43 days
Title
Changes from Baseline in Levels of Protein Markers in Buccal Cell
Description
Summary assessment of changes in levels of protein markers in buccal cells
Time Frame
At baseline and up to 43 days
Title
Changes from Baseline in Gene Expression in Buccal Cells
Description
Summary assessment of changes in gene expression in buccal cells
Time Frame
At baseline and up to 43 days
Title
Changes from Baseline in Frataxin Levels in Platelets
Description
Summary assessment of changes in frataxin levels in platelets
Time Frame
At baseline and up to 13 days
Title
Changes from Baseline in Gene Expression in Whole Blood
Description
Summary assessment of changes in gene expression in whole blood
Time Frame
At baseline and up to 16 days
Title
Changes from Baseline in Frataxin Levels in Skin Punch Cells
Description
Summary assessment of changes in frataxin levels in skin punch cells
Time Frame
At baseline and up to 13 days
Title
Changes from Baseline in Levels of Defined Protein Markers in Blood
Description
Summary assessment of changes in levels of defined protein markers in blood
Time Frame
At baseline and up to 16 days
Title
Changes from Baseline in Levels of Specialized Lipids in Blood
Description
Summary assessment of changes in levels of specialized lipids in blood
Time Frame
At baseline and up to 16 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Subject has genetically confirmed Friedreich's ataxia diagnosis manifested by homozygous GAA repeat expansions, with repeat sizing (if available) included on diagnostic report.
Subject is male or female, 18 years of age or older at screening
Subject must have a mFARS_neuro score ≥ 20 and be able to traverse a distance of 25 feet with or without some assistive device (cane, walker, crutches, self-propelled wheelchair) and (a) be able to sit upright with thighs together and arms crossed without requiring support on more than two sides; (b) be able to transfer from bed to chair independently or with assistance if, in the opinion of the principal investigator, the degree of physical disability does not result in undue risk to the subject while participating in the study; and (c) perform basic daily care, such as feeding themselves and personal hygiene, with minimal assistance.
Subjects must weigh > 40 kilograms (kg).
Exclusion Criteria:
Subjects who had a serious adverse event (SAE), an adverse event (AE) that is Grade 3 or higher according to the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 (or higher), or an AE considered clinically significant during participation in CLIN-1601-101 (NCT04176991).
Subjects who are confirmed as compound heterozygous (GAA repeat expansion on only one allele) for Friedreich's ataxia.
Subject use of 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 3 months prior to screening.
Subject use of daily biotin supplementation that exceeds 30 mcg/day, either as part of a multivitamin or as a standalone supplement, within 7 days prior to study drug administration and/or throughout the entire study.
Subject has clinically significant arrhythmia on electrocardiogram (ECG), or evidence of predisposition to significant ventricular arrhythmia on ECG, or evidence of active and unstable coronary artery disease.
Male subject who has a QT interval corrected for heart rate using Fridericia's formula (QTcF) > 450 milliseconds or female subject who has a QTcF > 470 milliseconds on an ECG.
Subject has a screening echocardiogram left ventricular ejection fraction < 45 percent.
Subject has a history of aspiration, aspiration pneumonia, or recurrent episodes of pneumonia (greater than or equal to 2 episodes of pneumonia) within the last 12 months.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Magdy Shenouda, M.D.
Organizational Affiliation
Clinilabs, Inc.
Official's Role
Principal Investigator
Facility Information:
Facility Name
Clinilabs Drug Development Corporation
City
Eatontown
State/Province
New Jersey
ZIP/Postal Code
07724
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
21315377
Citation
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.
Results Reference
background
PubMed Identifier
22752493
Citation
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.
Results Reference
background
PubMed Identifier
3178453
Citation
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.
Results Reference
background
PubMed Identifier
8797541
Citation
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.
Results Reference
background
PubMed Identifier
23691127
Citation
Plasterer HL, Deutsch EC, Belmonte M, Egan E, Lynch DR, Rusche JR. Development of frataxin gene expression measures for the evaluation of experimental treatments in Friedreich's ataxia. PLoS One. 2013 May 17;8(5):e63958. doi: 10.1371/journal.pone.0063958. Print 2013.
Results Reference
background
Links:
URL
http://www.curefa.org/
Description
Friedreich's Ataxia Research Alliance
Learn more about this trial
Multiple Ascending Dose Study of CTI-1601 Versus Placebo in Subjects With Friedreich's Ataxia
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