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

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

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.

Study Overview

• Status: Completed
• Conditions: Covid19; Stage 1 Acute Kidney Injury
• Intervention / Treatment: Drug: MIB-626; Drug: Placebo; Other: Home Treatment

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • The Brigham and Women's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MIB-626; 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; 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.; Other Names: NAD-boosting drug
Placebo Comparator: Placebo Tablet; 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; Subjects will be randomized to receive either the placebo or 1000-mg MIB-626 twice daily orally.
Other: Home Treatment; 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; 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.; Other Names: NAD-boosting drug; Drug: Placebo; Subjects will be randomized to receive either the placebo or 1000-mg MIB-626 twice daily orally.; Other: Home Treatment; 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.

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression in the stage of acute kidney injury increase in serum creatinine OR serum creatinine > 4.0 mg/dL OR need	Progression in the stage of acute kidney injury	enrollment to 14 days or hospital discharge, or death, whichever comes first
The WHO 8-point Ordinal Scale of Clinical Status	The WHO 8-point Ordinal Scale of Clinical Status	enrollment to 14 days or hospital discharge, or death, whichever comes first
Change from baseline in Modified Sequential Organ Failure Assessment (SOFA) Score (SOFA) Score	Change from baseline in Modified Sequential Organ Failure Assessment (SOFA) Score	enrollment to 14 days or hospital discharge, or death, whichever comes first
The number and proportion of patients requiring mechanical ventilation, hemodialysis, or transferred to ICU	The number and proportion of patients requiring mechanical ventilation, hemodialysis, or transferred to ICU	enrollment to 14 days or hospital discharge, or death, whichever comes first
The number and proportion of patients requiring hemodialysis	The number and proportion of patients requiring hemodialysis	enrollment to 14 days or hospital discharge, or death, whichever comes first
The number and proportion of patients who die	The number and proportion of patients who die	enrollment to 14 days or hospital discharge, or death, whichever comes first
The number of days it takes for the temperature to return to normal (<99F)	The number of days it takes for the temperature to return to normal (<99F)	enrollment to 14 days or hospital discharge, or death, whichever comes first
The length of hospital stay	The length of hospital stay	enrollment to 14 days or hospital discharge, or death, whichever comes first

Collaborators and Investigators

• Sponsor: Metro International Biotech, LLC
• Investigators: Principal Investigator: Shalender Bhasin, MD, Brigham and Women's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 26, 2021
• Primary Completion (Actual): August 17, 2023
• Study Completion (Actual): August 17, 2023

Study Registration Dates

• First Submitted: March 18, 2021
• First Submitted That Met QC Criteria: September 7, 2021
• First Posted (Actual): September 9, 2021

Study Record Updates

• Last Update Posted (Actual): August 27, 2024
• Last Update Submitted That Met QC Criteria: August 14, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Covid19; MIB-626; Early Acute Kidney Injury; NAD-boosting drug
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Kidney Diseases; Urologic Diseases; Renal Insufficiency; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; COVID-19; Acute Kidney Injury
• Other Study ID Numbers: MIB-626-202

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data will not be shared

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No