Phase 2a MIB-626 vs. Placebo COVID-19

Study Overview
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Brief Summary
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The proposed phase 2a trial will determine whether MIB-626 treatment in adults with COVID-19 infection and stage 1 acute kidney injury is more efficacious than placebo in preventing worsening of kidney function, as assessed by longitudinal changes in serum creatinine concentration, and in attenuating the inflammatory response to the infection.

Detailed Description
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This is a two-center, randomized, double-blind, placebo-controlled, parallel-group, phase 2a study that will determine the efficacy and safety of MIB-626 treatment relative to placebo in adult patients with COVID-19 infection and stage 1 acute kidney injury. Hospitalized adult patients with a confirmed or suspected diagnosis of COVID-19 infection will be screened for conformity to inclusion and exclusion criteria and those meeting eligibility criteria on screening will be offered participation in the study. Fifty participants, who meet all the eligibility criteria, and are able and willing to provide informed consent, will be randomized, stratified by sex, remdesivir use, and trial site, in a 3:2 ratio to receive either MIB-626 1.0 g orally or matching placebo twice daily for 14 days. The participants, who are discharged from the hospital before the completion of the 14-day intervention period, will be provided sufficient study medication to take home with them so they can continue to take the medication twice daily for the remaining duration of the 14-day intervention period.

Official Title
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A Phase 2a Randomized Controlled Trial of MIB-626 (NAD-boosting Drug) vs. Placebo in Adults With COVID-19 Infection and Early Acute Kidney Injury

Conditions
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Covid19, Stage 1 Acute Kidney Injury

Intervention / Treatment
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* Drug: MIB-626
* Drug: Placebo
* Other: Home Treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A man or a woman, 18 years or older Willing and able to provide informed consent, or with a legal representative who can provide informed consent with participant's assent Has Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 infection confirmed by an approved diagnostic test before randomization Currently hospitalized Documented increase in serum creatinine of 0.3 mg/dL or 50%-99% over baseline (baseline either based on admission serum creatinine or known pre-admission baseline, defined as most recent previous measurement) Participant or legal representative has read and signed the Informed Consent Form (ICF) after the nature of the study has been fully explained Is willing and able to provide authorization for the use and disclosure of personal health information in accordance with Health Insurance Portability and Accountability Act (HIPAA) Patients who are receiving remdesivir as a part of their clinical care or are in clinical trials of remdesivir or other antiviral drugs may be allowed if they meet other eligibility criteria Patients, who are participating in observational studies or studies of nonpharmacological interventions, will be allowed to participate Not be pregnant and not planning to become pregnant over the next 6 months Exclusion Criteria: In the intensive care unit at the time of screening or prior to randomization Requiring mechanical ventilation at the time of screening or prior to randomization Has baseline estimated glomerular filtration rate < 30 ml/min/1.73m2 Has a history of kidney transplantation or hemodialysis treatment or receiving or expected to receive hemodialysis or peritoneal dialysis at screening and prior to randomization Is on mechanical ventilation Has a contraindication for MIB-626 or its inert ingredients Has a diagnosis of lupus nephritis, polycystic kidney disease, other glomerular disease (other than diabetes) Has AST or ALT > 3 times the upper limit of normal Has other medical condition which, in the opinion of the Principal Investigator, would jeopardize the safety of the study subject or impact the validity of the study results Will exclude patients, who are receiving or are enrolled in placebo-controlled intervention trials of anti-inflammatory or immunomodulatory agents, such as tocilizumab. Occasional use of acetaminophen and nonsteroidal anti-inflammatory drugs, such as ibuprofen, for fever or headache is permitted.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This will be a two center, randomized, double-blind, placebo- controlled, parallel group, efficacy trial to determine the efficacy of MIB-626 treatment relative to placebo in adult patients with COVID-19 infection and stage 1 acute kidney injury. Participants will be screened for eligibility and those meeting eligibility criteria will be offered participation in the study. The subjects will be randomized by minimization to receive MIB-626 or placebo twice daily for up to 14 days. The participants will be followed for 28 days after the administration of the last dose of the investigational product. Kidney function will be ascertained by daily measurements of serum creatinine, which is the standard of care in hospitalized patients with COVID-19.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MIB-626<br>Oral administration of MIB-626 substantially raises the intracellular NAD+ levels and activates signaling mechanisms that regulate inflammation and cell survival, downregulates the NLRP3 inflammasome, and attenuates the inflammatory response in a number of experimental models, and protects against tissue damage induced by pro-inflammatory cytokines. | Drug: MIB-626<br>* Fifty participants will be randomized, stratified by sex, remdesivir use, and trial site, in a 3:2 ratio to receive either MIB-626 1.0 g orally or matching placebo twice daily for 14 days.<br>* Other names: NAD-boosting drug;|
| Placebo Comparator: Placebo Tablet<br>A placebo control will be supplied. Participants randomized to placebo will receive matching tablet. Matching placebo tablets will be provided by the study's Sponsor, Metro International Biotech, LLC. | Drug: Placebo<br>* Subjects will be randomized to receive either the placebo or 1000-mg MIB-626 twice daily orally.<br>|
| Other: Home Treatment<br>Participants, who are discharged from the hospital before the completion of the 14-day intervention period, will be provided sufficient study medication to take home with them so they can continue to take the medication twice daily for the remaining duration of the 14-day intervention period. | Drug: MIB-626<br>* Fifty participants will be randomized, stratified by sex, remdesivir use, and trial site, in a 3:2 ratio to receive either MIB-626 1.0 g orally or matching placebo twice daily for 14 days.<br>* Other names: NAD-boosting drug;Drug: Placebo<br>* Subjects will be randomized to receive either the placebo or 1000-mg MIB-626 twice daily orally.<br>Other: Home Treatment<br>* Participants, who are discharged from the hospital before the completion of the 14-day intervention period, will be provided sufficient study medication to take home with them so they can continue to take the medication twice daily for the remaining duration of the 14-day intervention period.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in serum cystatin C levels | Change from baseline in serum cystatin C levels | enrollment to 14 days or hospital discharge, or death, whichever comes first | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline to peak concentrations of inflammatory biomarkers (IL6, TNF-alpha, hsCRP, Angiotensin 2 to Angiotensin1, 7 ratio, ACE 2) | Change from baseline to peak concentrations of inflammatory biomarkers (IL6, TNF-alpha, hsCRP, Angiotensin 2 to Angiotensin1, 7 ratio, ACE 2) | enrollment to 14 days or hospital discharge, or death, whichever comes first | 
| The trajectory of change from baseline in concentrations of inflammatory biomarkers (IL6, TNF-alpha, hsCRP, Angiotensin 2 to Angiotensin1, 7 ratio, ACE 2) | The trajectory of change from baseline in concentrations of inflammatory biomarkers (IL6, TNF-alpha, hsCRP, Angiotensin 2 to Angiotensin1, 7 ratio, ACE 2) | enrollment to 14 days or hospital discharge, or death, whichever comes first | 
| Change from baseline in markers of endothelial damage (vWF, VCAM, PAI-1) | Change from baseline in markers of endothelial damage (vWF, VCAM, PAI-1) | enrollment to 14 days or hospital discharge, or death, whichever comes first | 
| Change from baseline in markers of microvascular thrombosis (D-dimer, fibrinogen) | Change from baseline in markers of microvascular thrombosis (D-dimer, fibrinogen) | enrollment to 14 days or hospital discharge, or death, whichever comes first | 
| The trajectory of change in plasma (NGAL, KIM-1) and urinary (KIM-1, NGAL, albumin) biomarkers of acute kidney injury | The trajectory of change in plasma (NGAL, KIM-1) and urinary (KIM-1, NGAL, albumin) biomarkers of acute kidney injury | enrollment to 14 days or hospital discharge, or death, whichever comes first | 
| Change in urinary albumin concentration (normalized to urine creatinine) from enrollment to peak during hospitalization | Change in urinary albumin concentration (normalized to urine creatinine) from enrollment to peak during hospitalization | enrollment to 14 days or hospital discharge, or death, whichever comes first | 
| Change from baseline in oxygen saturation | Change from baseline in oxygen saturation | enrollment to 14 days or hospital discharge, or death, whichever comes first | 
| Change in high sensitivity troponin-1 concentration from enrollment to peak during hospitalization (measured daily in stored biospecimens) | Change in high sensitivity troponin-1 concentration from enrollment to peak during hospitalization (measured daily in stored biospecimens) | enrollment to 14 days or hospital discharge, or death, whichever comes first | 
| Change from baseline in intracellular NAD+ concentrations in blood during the 14-day treatment period in a subset of study participants | Change from baseline in intracellular NAD+ concentrations in blood during the 14-day treatment period in a subset of study participants | enrollment to 14 days or hospital discharge, or death, whichever comes first | 
| Circulating concentrations of MIB-626 and its key metabolites P2Y, NAAD, NAM, 1-methylnicotinamide during the 14-day treatment period | Circulating concentrations of MIB-626 and its key metabolites P2Y, NAAD, NAM, 1-methylnicotinamide during the 14-day treatment period | enrollment to 14 days or hospital discharge, or death, whichever comes first | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MIB-626, Covid19, Early Acute Kidney Injury, NAD-boosting drug