NAD+ Precursor Supplementation in Friedreich's Ataxia

NCT04817111 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 19-016525MIB-626-201
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

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.

Conditions

Friedreich Ataxia

Outcome Measures

Primary Outcomes (1)

• 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.

  14 Days

Secondary Outcomes (4)

• Cardiac 31-Phosphorus-Magnetic Resonance Spectroscopy (MRS): Phosphocreatine (PCr)/Adenosine Tri-Phosphate (ATP) Ratio

  Change from baseline to 14 days.

• Post-Exercise Creatine Chemical Exchange Saturation Transfer (CrCEST) Magnetic Resonance Imaging (MRI)

  Change from baseline to 14 days.

• Grip Strength

  Change from baseline to 14 days.

• Concentration of Nicotinamide Adenine Dinucleotide (NAD+) in Whole Blood

  Change from baseline to 14 days.

Study Arms (1)

Open Label - MIB-626

OTHER

MIB-626

Drug: MIB-626

Interventions

MIB-626 DRUG

Two (2) 500 mg Tablets, By Mouth, Daily

Open Label - MIB-626

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Metro International Biotech, LLC: lead
• Children's Hospital of Philadelphia: collaborator

Study Sites (1)

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (3)

• 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.

  PMID: 27812541 BACKGROUND

• 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.

  BACKGROUND

• 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.

  PMID: 27648458 BACKGROUND

MeSH Terms

Conditions

Friedreich Ataxia

Condition Hierarchy (Ancestors)

Spinocerebellar Degenerations; Cerebellar Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Spinal Cord Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Mitochondrial Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Dr. Shana McCormack
• Organization: Children's Hospital of Philadelphia

mccormacks1@email.chop.edu

215-590-3174

Study Officials

• Shana E McCormack, MD

  Children's Hospital of Philadelphia

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Attending Physician

Model Details: Open Label, 14 Days (+/- 2 Days)

Study Record Dates

• First Submitted: March 10, 2021
• First Posted: March 25, 2021
• Study Start: May 17, 2021
• Primary Completion: May 19, 2022
• Study Completion: May 19, 2022
• Last Updated: July 17, 2023
• Results First Posted: July 17, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)