Back to resultsSingle 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, 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 minimal 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 (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 are confirmed as compound heterozygous (GAA repeat expansion on only one allele) for Friedreich's ataxia.
- Subject requires use of amiodarone.
- Subject used erythropoietin, etravirine, or gamma interferon within 3 months prior to screening.
- Subject use of investigational drug (other than CTI-1601) or device within 90 days 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 an ECG QTcF > 450 milliseconds or female subject who has an ECG QTcF > 470 milliseconds.
- Subject has a screening echocardiogram 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.
- Subjects with known or suspected chronic use of cannabinoid products.
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 the Participants with Treatment Emergent Adverse Events
Number of 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 22.0)
Secondary Outcome Measures
Pharmacokinetics - Area under the concentration-time curve after a single dose
Summary assessment of changes in the area under the concentration-time curve after a single dose
Pharmacokinetics - Maximum observed plasma concentration after a single dose
Summary assessment of changes in the maximum observed plasma concentration after a single dose
Pharmacokinetics - Time to reach maximum plasma concentration after a single dose
Summary assessment of changes in time to reach maximum plasma concentration after a single dose
Pharmacokinetics - Area under the concentration-time curve from time 0 to infinity
Summary assessment of changes in the area under the concentration-time curve from time 0 to infinity
Pharmacokinetics - Area under the concentration-time curve from time 0 to the last measurable time point
Summary assessment of changes in the Area under the concentration-time curve from time 0 to the last measurable time point
Pharmacokinetics - Apparent total plasma clearance
Summary assessment of changes in the apparent total plasma clearance
Pharmacokinetics - Terminal half-life estimation
Summary assessment of changes in the terminal half-life estimation
Pharmacokinetics - Apparent volume of distribution
Summary assessment of changes in the apparent volume of distribution
Changes from Baseline in Frataxin Levels in Buccal Cells
Summary assessment of changes in frataxin levels in buccal cells
Changes from Baseline in Frataxin Levels in Whole Blood
Summary assessment of changes in frataxin levels in whole blood
Changes in Gene Expression Profiling
Summary assessment of changes in gene expression levels
Full Information
NCT ID
NCT04176991
First Posted
November 14, 2019
Last Updated
November 9, 2020
Sponsor
Larimar Therapeutics, Inc.
Collaborators
Veristat, Inc., Metrum Research Group, LLC
1. Study Identification
Unique Protocol Identification Number
NCT04176991
Brief Title
Single Ascending Dose Study of CTI-1601 Versus Placebo in Subjects With Friedreich's Ataxia
Official Title
A Phase 1 Single 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
November 2020
Overall Recruitment Status
Completed
Study Start Date
December 11, 2019 (Actual)
Primary Completion Date
October 31, 2020 (Actual)
Study Completion Date
October 31, 2020 (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 single ascending doses of CTI-1601 in participants with Friedreich's ataxia
Detailed Description
Single Ascending Dose (SAD), Double-Blind, Placebo Controlled Study.
To evaluate the safety and tolerability of single ascending doses of CTI-1601 in subjects with Friedreich's ataxia.
Secondary Objectives:
To evaluate the pharmacokinetics (PK) of CTI-1601 following increasing single doses of subcutaneously (SC) administered CTI-1601.
To evaluate the pharmacodynamics (PD) of CTI-1601 following increasing single doses of SC administered CTI-1601.
CTI-1601 or Placebo - Dose/Mode of Administration: Single Dose/Subcutaneous
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
28 (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 the Participants with Treatment Emergent Adverse Events
Time Frame
Through study completion, an average of 70 days
Title
Number of 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 22.0)
Time Frame
Through study completion, an average of 70 days
Secondary Outcome Measure Information:
Title
Pharmacokinetics - Area under the concentration-time curve after a single dose
Description
Summary assessment of changes in the area under the concentration-time curve after a single dose
Time Frame
Up to 48 hours
Title
Pharmacokinetics - Maximum observed plasma concentration after a single dose
Description
Summary assessment of changes in the maximum observed plasma concentration after a single dose
Time Frame
Up to 48 hours
Title
Pharmacokinetics - Time to reach maximum plasma concentration after a single dose
Description
Summary assessment of changes in time to reach maximum plasma concentration after a single dose
Time Frame
Up to 48 hours
Title
Pharmacokinetics - Area under the concentration-time curve from time 0 to infinity
Description
Summary assessment of changes in the area under the concentration-time curve from time 0 to infinity
Time Frame
48 hours
Title
Pharmacokinetics - Area under the concentration-time curve from time 0 to the last measurable time point
Description
Summary assessment of changes in the Area under the concentration-time curve from time 0 to the last measurable time point
Time Frame
48 hours
Title
Pharmacokinetics - Apparent total plasma clearance
Description
Summary assessment of changes in the apparent total plasma clearance
Time Frame
48 hours
Title
Pharmacokinetics - Terminal half-life estimation
Description
Summary assessment of changes in the terminal half-life estimation
Time Frame
48 hours
Title
Pharmacokinetics - Apparent volume of distribution
Description
Summary assessment of changes in the apparent volume of distribution
Time Frame
48 hours
Title
Changes from Baseline in Frataxin Levels in Buccal Cells
Description
Summary assessment of changes in frataxin levels in buccal cells
Time Frame
At baseline and up to 10 days
Title
Changes from Baseline in Frataxin Levels in Whole Blood
Description
Summary assessment of changes in frataxin levels in whole blood
Time Frame
At baseline and up to 10 days
Title
Changes in Gene Expression Profiling
Description
Summary assessment of changes in gene expression levels
Time Frame
At baseline and up to 10 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, 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 minimal 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 (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 are confirmed as compound heterozygous (GAA repeat expansion on only one allele) for Friedreich's ataxia.
Subject requires use of amiodarone.
Subject used erythropoietin, etravirine, or gamma interferon within 3 months prior to screening.
Subject use of investigational drug (other than CTI-1601) or device within 90 days 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 an ECG QTcF > 450 milliseconds or female subject who has an ECG QTcF > 470 milliseconds.
Subject has a screening echocardiogram 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.
Subjects with known or suspected chronic use of cannabinoid products.
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
Single Ascending Dose Study of CTI-1601 Versus Placebo in Subjects With Friedreich's Ataxia
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