NAD+ Precursor Supplementation in Friedreich's Ataxia

A Phase 2a Study of NAD+ Precursor Supplementation in Friedreich's Ataxia

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.

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.

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.