Friedreich AtaxiaPhase 2NCT04817111
NAD+ Precursor Supplementation in Friedreich's Ataxia
A Phase 2 study testing MIB-626 in people with Friedreich Ataxia, run by Metro International Biotech, LLC at 1 site in United States.
Trial 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%. Read more about this study
- Who is it for?
- Ages 18 to 64 years
- Conditions the study is for
- Friedreich Ataxia
- What is being tested?
- MIB-626
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- 17 May 2021to 19 May 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 64 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Molecular diagnosis of Friedreich's Ataxia (FA).
- Males and females, ages 18 years to < 65 years.
Who cannot join
- 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.
Show all 10Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
About this study
Official title: 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.
Read the 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.
- Conditions
- Friedreich Ataxia
- Being tested
- MIB-626
- Medical subject headings
- Friedreich Ataxia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MIB-626Drug
Two (2) 500 mg Tablets, By Mouth, Daily
| Study group | Role | What they receive |
|---|---|---|
| Open Label - MIB-626 | Other | MIB-626 Receives: Drug: MIB-626 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 14 Days
Secondary outcomes (4)
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.
Measured: Change from baseline to 14 days.
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).
Measured: Change from baseline to 14 days.
Grip Strength
Assess within-participant changes in grip strength (via hand grip dynamometry) before and after treatment with MIB-626.
Measured: Change from baseline to 14 days.
Concentration of Nicotinamide Adenine Dinucleotide (NAD+) in Whole Blood
Measure the concentration of NAD+ in whole blood before and after treatment with MIB-626.
Measured: Change from baseline to 14 days.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Mar 2021
- Study start17 May 2021
- Primary completion19 May 2022
- Study completion19 May 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Friedreich AtaxiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Open Label, 14 Days (+/- 2 Days)
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Metro International Biotech, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Children's Hospital of Philadelphia
- Responsible party
- Principal investigator, Shana McCormack, Children's Hospital of Philadelphia
- Investigators
- Shana E McCormack, MD, Principal investigator, Children's Hospital of Philadelphia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04817111
- Sponsor's protocol ID
- 19-016525
- Other IDs
- MIB-626-201
- Status last verified
- Jul 2023
- First submitted
- 10 Mar 2021
- Last updated
- 17 Jul 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: IPD may be available with appropriate regulatory approvals.
Publications
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.
PubMed 27812541Bagga 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.
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.
PubMed 27648458
Study at a glance
From the registry record, last updated by the sponsor on 17 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2a Study of NAD+ Precursor Supplementation in Friedreich's Ataxia
- ClinicalTrials.gov ID
- NCT04817111
- Acronym / sponsor ID
- 19-016525
- Conditions
- Friedreich Ataxia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Metro International Biotech, LLCIndustry (pharma, biotech, devices)
- Collaborators
- Children's Hospital of Philadelphia
- Study start
- 17 May 2021 (actual)
- Primary completion
- 19 May 2022 (actual)
- Study completion
- 19 May 2022 (actual)
- First posted
- 25 Mar 2021 (actual)
- Results
- Posted 17 Jul 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Open Label, 14 Days (+/- 2 Days)
| Arm | Type | Receives |
|---|---|---|
| Open Label - MIB-626 | Other | Drug: MIB-626MIB-626 |
Who may qualify
- Ages
- 18 to 64 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Molecular diagnosis of Friedreich's Ataxia (FA).
- Males and females, ages 18 years to < 65 years.
Key exclusion criteria (10 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MIB-626Two (2) 500 mg Tablets, By Mouth, Daily | Drug | Open Label - MIB-626 |
Primary outcome
Percentage of Individuals With Treatment-emergent Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 5.0.
Time frame: 14 Days
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.
4 secondary outcomes
Cardiac 31-Phosphorus-Magnetic Resonance Spectroscopy (MRS): Phosphocreatine (PCr)/Adenosine Tri-Phosphate (ATP) Ratio
Time frame: Change from baseline to 14 days.
Post-Exercise Creatine Chemical Exchange Saturation Transfer (CrCEST) Magnetic Resonance Imaging (MRI)
Time frame: Change from baseline to 14 days.
Grip Strength
Time frame: Change from baseline to 14 days.
Concentration of Nicotinamide Adenine Dinucleotide (NAD+) in Whole Blood
Time frame: Change from baseline to 14 days.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jul 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 27812541DeBrosse 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.
- BackgroundBagga 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: PubMed 27648458Patel 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.
- Individual participant dataSharing planned: No. IPD may be available with appropriate regulatory approvals.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Shana E McCormack, MD principal investigator
Children's Hospital of Philadelphia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing MIB-626 in people with Friedreich Ataxia, run by Metro International Biotech, LLC at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Jul 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Individuals With Treatment-emergent Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 5.0. (time frame: 14 Days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04817111, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jul 2023.