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NAD+ Precursor Supplementation in Friedreich's Ataxia

Primary Purpose

Friedreich Ataxia

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
MIB-626
Sponsored by
Metro International Biotech, LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Friedreich Ataxia

Eligibility Criteria

18 Years - 64 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Molecular diagnosis of Friedreich's Ataxia (FA).
  • Males and females, ages 18 years to < 65 years.

Exclusion Criteria:

  • Known sensitivity to nicotinamide-containing compounds.
  • Concurrent use of Vitamin B3 supplements and/or any medications likely to increase risk of MIB-626 toxicity.
  • HgbA1c > (great than or equal to) 8.5% and or Diabetes Mellitus (DM) requiring insulin or insulin secretagogue.
  • Kidney disease (Estimated Glomerular Filtration Rate (eGFR) < 60 ml/min/1.73 m2) using serum creatinine and MDRD equation. The eGFR levels will be calculated using the Modified Diet in Renal Disease Study (MDRD) equation, which is the equation used by the Children's Hospital Of Philadelphia laboratory.
  • Liver disease (Aspartate Aminotransferase (AST)/Alanine Aminotransferase (ALT) > 3 x Upper Limit of Normal)
  • Severe co-existing cardiac disease (Ejection Fraction (EF) < 40%, known arrhythmia) as demonstrated by an echocardiogram within 12 months of screening.
  • Any contraindication to MRI, including spinal rods (related to unknown safety considerations for cardiac 31-Phosphorus -MRS).
  • Use of any investigational agent within 4 weeks of enrollment.
  • Females: Pregnant/lactating or planning to become pregnant during their participation.
  • Any medical condition that, in the opinion of the investigator, will interfere with the safe completion of the study.

Sites / Locations

  • The Children's Hospital of Philadelphia

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

Open Label - MIB-626

Arm Description

MIB-626

Outcomes

Primary Outcome Measures

Percentage of Individuals With Treatment-emergent Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 5.0.
Safety will be monitored through collection of laboratory assessments (CBC, complete metabolic profile, lipid profile, HbA1c), vital signs (heart rate, blood pressure), and ECG, all of which will be reviewed for clinically relevant abnormalities, and standardized assessment of symptoms. We report the proportion of individuals who had at least one treatment-emergent adverse event of Grade 1 or higher.

Secondary Outcome Measures

Cardiac 31-Phosphorus-Magnetic Resonance Spectroscopy (MRS): Phosphocreatine (PCr)/Adenosine Tri-Phosphate (ATP) Ratio
Measure the within-participant change in PCr/ATP ratio before and after treatment with MIB-626.
Post-Exercise Creatine Chemical Exchange Saturation Transfer (CrCEST) Magnetic Resonance Imaging (MRI)
Assess the within-participant change in skeletal muscle post-exercise CrCEST recovery (an index of skeletal muscle mitochondrial oxidative phosphorylation capacity).
Grip Strength
Assess within-participant changes in grip strength (via hand grip dynamometry) before and after treatment with MIB-626.
Concentration of Nicotinamide Adenine Dinucleotide (NAD+) in Whole Blood
Measure the concentration of NAD+ in whole blood before and after treatment with MIB-626.

Full Information

First Posted
March 10, 2021
Last Updated
July 12, 2023
Sponsor
Metro International Biotech, LLC
Collaborators
Children's Hospital of Philadelphia
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1. Study Identification

Unique Protocol Identification Number
NCT04817111
Brief Title
NAD+ Precursor Supplementation in Friedreich's Ataxia
Official Title
A Phase 2a Study of NAD+ Precursor Supplementation in Friedreich's Ataxia
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Completed
Study Start Date
May 17, 2021 (Actual)
Primary Completion Date
May 19, 2022 (Actual)
Study Completion Date
May 19, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Metro International Biotech, LLC
Collaborators
Children's Hospital of Philadelphia

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The primary objective is to test the safety and tolerability of short-term therapy with a nicotinamide adenine dinucleotide (NAD+) precursor (MIB-626) in adults with Friedreich's Ataxia (FA) without overt heart failure and with a left ventricular ejection fraction ≥ 40%. A key secondary objective is to test the effects of MIB-626 on cardiac and skeletal muscle bioenergetics.
Detailed Description
The primary focus for this protocol is safety and tolerability. We will systematically assess for adverse events using a safety monitoring uniform report form. We will also use cardiac 31-Phosphorus-Magnetic Resonance Spectroscopy (MRS) to measure the Phosphocreatine(PCr)/Adenosine triphosphate (ATP)- γ ratio before and after treatment with MIB-626. In addition, if time permits we will use proton (1H)-MRS to measure skeletal muscle nicotinamide adenine dinucleotide (NAD+) before and after treatment.

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
Other
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
Open Label, 14 Days (+/- 2 Days)
Masking
None (Open Label)
Allocation
N/A
Enrollment
7 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Open Label - MIB-626
Arm Type
Other
Arm Description
MIB-626
Intervention Type
Drug
Intervention Name(s)
MIB-626
Intervention Description
Two (2) 500 mg Tablets, By Mouth, Daily
Primary Outcome Measure Information:
Title
Percentage of Individuals With Treatment-emergent Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 5.0.
Description
Safety will be monitored through collection of laboratory assessments (CBC, complete metabolic profile, lipid profile, HbA1c), vital signs (heart rate, blood pressure), and ECG, all of which will be reviewed for clinically relevant abnormalities, and standardized assessment of symptoms. We report the proportion of individuals who had at least one treatment-emergent adverse event of Grade 1 or higher.
Time Frame
14 Days
Secondary Outcome Measure Information:
Title
Cardiac 31-Phosphorus-Magnetic Resonance Spectroscopy (MRS): Phosphocreatine (PCr)/Adenosine Tri-Phosphate (ATP) Ratio
Description
Measure the within-participant change in PCr/ATP ratio before and after treatment with MIB-626.
Time Frame
Change from baseline to 14 days.
Title
Post-Exercise Creatine Chemical Exchange Saturation Transfer (CrCEST) Magnetic Resonance Imaging (MRI)
Description
Assess the within-participant change in skeletal muscle post-exercise CrCEST recovery (an index of skeletal muscle mitochondrial oxidative phosphorylation capacity).
Time Frame
Change from baseline to 14 days.
Title
Grip Strength
Description
Assess within-participant changes in grip strength (via hand grip dynamometry) before and after treatment with MIB-626.
Time Frame
Change from baseline to 14 days.
Title
Concentration of Nicotinamide Adenine Dinucleotide (NAD+) in Whole Blood
Description
Measure the concentration of NAD+ in whole blood before and after treatment with MIB-626.
Time Frame
Change from baseline to 14 days.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
64 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Molecular diagnosis of Friedreich's Ataxia (FA). Males and females, ages 18 years to < 65 years. Exclusion Criteria: Known sensitivity to nicotinamide-containing compounds. Concurrent use of Vitamin B3 supplements and/or any medications likely to increase risk of MIB-626 toxicity. HgbA1c > (great than or equal to) 8.5% and or Diabetes Mellitus (DM) requiring insulin or insulin secretagogue. Kidney disease (Estimated Glomerular Filtration Rate (eGFR) < 60 ml/min/1.73 m2) using serum creatinine and MDRD equation. The eGFR levels will be calculated using the Modified Diet in Renal Disease Study (MDRD) equation, which is the equation used by the Children's Hospital Of Philadelphia laboratory. Liver disease (Aspartate Aminotransferase (AST)/Alanine Aminotransferase (ALT) > 3 x Upper Limit of Normal) Severe co-existing cardiac disease (Ejection Fraction (EF) < 40%, known arrhythmia) as demonstrated by an echocardiogram within 12 months of screening. Any contraindication to MRI, including spinal rods (related to unknown safety considerations for cardiac 31-Phosphorus -MRS). Use of any investigational agent within 4 weeks of enrollment. Females: Pregnant/lactating or planning to become pregnant during their participation. Any medical condition that, in the opinion of the investigator, will interfere with the safe completion of the study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Shana E McCormack, MD
Organizational Affiliation
Children's Hospital of Philadelphia
Official's Role
Principal Investigator
Facility Information:
Facility Name
The Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
IPD may be available with appropriate regulatory approvals.
Citations:
PubMed Identifier
27812541
Citation
DeBrosse C, Nanga RPR, Wilson N, D'Aquilla K, Elliott M, Hariharan H, Yan F, Wade K, Nguyen S, Worsley D, Parris-Skeete C, McCormick E, Xiao R, Cunningham ZZ, Fishbein L, Nathanson KL, Lynch DR, Stallings VA, Yudkoff M, Falk MJ, Reddy R, McCormack SE. Muscle oxidative phosphorylation quantitation using creatine chemical exchange saturation transfer (CrCEST) MRI in mitochondrial disorders. JCI Insight. 2016 Nov 3;1(18):e88207. doi: 10.1172/jci.insight.88207.
Results Reference
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Citation
Bagga P, Wilson N., DeBrosse D., Hariharan H., Reddy R., editor. In vivo detection of NAD+ in human calf muscle at 7T using 28-channel knee volume coil. International Society for Magnetic Resonance in Medicine; 2019; Montreal, Canada.
Results Reference
background
PubMed Identifier
27648458
Citation
Patel M, Isaacs CJ, Seyer L, Brigatti K, Gelbard S, Strawser C, Foerster D, Shinnick J, Schadt K, Yiu EM, Delatycki MB, Perlman S, Wilmot GR, Zesiewicz T, Mathews K, Gomez CM, Yoon G, Subramony SH, Brocht A, Farmer J, Lynch DR. Progression of Friedreich ataxia: quantitative characterization over 5 years. Ann Clin Transl Neurol. 2016 Jul 25;3(9):684-94. doi: 10.1002/acn3.332. eCollection 2016 Sep.
Results Reference
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NAD+ Precursor Supplementation in Friedreich's Ataxia

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