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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05038488
Recruitment Status : Recruiting
First Posted : September 9, 2021
Last Update Posted : December 1, 2021
Sponsor:
Information provided by (Responsible Party):
Shalender Bhasin, Metro International Biotech, LLC

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Covid19 Stage 1 Acute Kidney Injury Drug: MIB-626 Drug: Placebo Other: Home Treatment Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention 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 (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Double blind
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : October 26, 2021
Estimated Primary Completion Date : April 28, 2022
Estimated Study Completion Date : August 20, 2022


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 Name: 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.

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 Name: 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.




Primary Outcome Measures :
  1. Change from baseline in serum cystatin C levels [ Time Frame: enrollment to 14 days or hospital discharge, or death, whichever comes first ]
    Change from baseline in serum cystatin C levels


Secondary Outcome Measures :
  1. Change from baseline to peak concentrations of inflammatory biomarkers (IL6, TNF-alpha, hsCRP, Angiotensin 2 to Angiotensin1, 7 ratio, ACE 2) [ Time Frame: enrollment to 14 days or hospital discharge, or death, whichever comes first ]
    Change from baseline to peak concentrations of inflammatory biomarkers (IL6, TNF-alpha, hsCRP, Angiotensin 2 to Angiotensin1, 7 ratio, ACE 2)

  2. The trajectory of change from baseline in concentrations of inflammatory biomarkers (IL6, TNF-alpha, hsCRP, Angiotensin 2 to Angiotensin1, 7 ratio, ACE 2) [ Time Frame: 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)

  3. Change from baseline in markers of endothelial damage (vWF, VCAM, PAI-1) [ Time Frame: enrollment to 14 days or hospital discharge, or death, whichever comes first ]
    Change from baseline in markers of endothelial damage (vWF, VCAM, PAI-1)

  4. Change from baseline in markers of microvascular thrombosis (D-dimer, fibrinogen) [ Time Frame: enrollment to 14 days or hospital discharge, or death, whichever comes first ]
    Change from baseline in markers of microvascular thrombosis (D-dimer, fibrinogen)

  5. The trajectory of change in plasma (NGAL, KIM-1) and urinary (KIM-1, NGAL, albumin) biomarkers of acute kidney injury [ Time Frame: 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

  6. Change in urinary albumin concentration (normalized to urine creatinine) from enrollment to peak during hospitalization [ Time Frame: 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

  7. Change from baseline in oxygen saturation [ Time Frame: enrollment to 14 days or hospital discharge, or death, whichever comes first ]
    Change from baseline in oxygen saturation

  8. Change in high sensitivity troponin-1 concentration from enrollment to peak during hospitalization (measured daily in stored biospecimens) [ Time Frame: 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)

  9. Change from baseline in intracellular NAD+ concentrations in blood during the 14-day treatment period in a subset of study participants [ Time Frame: 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

  10. Circulating concentrations of MIB-626 and its key metabolites P2Y, NAAD, NAM, 1-methylnicotinamide during the 14-day treatment period [ Time Frame: 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


Other Outcome Measures:
  1. Progression in the stage of acute kidney injury increase in serum creatinine OR serum creatinine > 4.0 mg/dL OR need [ Time Frame: enrollment to 14 days or hospital discharge, or death, whichever comes first ]
    Progression in the stage of acute kidney injury

  2. The WHO 8-point Ordinal Scale of Clinical Status [ Time Frame: enrollment to 14 days or hospital discharge, or death, whichever comes first ]
    The WHO 8-point Ordinal Scale of Clinical Status

  3. Change from baseline in Modified Sequential Organ Failure Assessment (SOFA) Score (SOFA) Score [ Time Frame: enrollment to 14 days or hospital discharge, or death, whichever comes first ]
    Change from baseline in Modified Sequential Organ Failure Assessment (SOFA) Score

  4. The number and proportion of patients requiring mechanical ventilation, hemodialysis, or transferred to ICU [ Time Frame: 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

  5. The number and proportion of patients requiring hemodialysis [ Time Frame: enrollment to 14 days or hospital discharge, or death, whichever comes first ]
    The number and proportion of patients requiring hemodialysis

  6. The number and proportion of patients who die [ Time Frame: enrollment to 14 days or hospital discharge, or death, whichever comes first ]
    The number and proportion of patients who die

  7. The number of days it takes for the temperature to return to normal (<99F) [ Time Frame: 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)

  8. The length of hospital stay [ Time Frame: enrollment to 14 days or hospital discharge, or death, whichever comes first ]
    The length of hospital stay



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05038488


Contacts
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Contact: Shalender Bhasin, MD 617 525 9150 sbhasin@bwh.harvard.edu
Contact: Deatrice S Moore 617 872 6096 dsmoore@bwh.harvard.edu

Locations
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United States, Massachusetts
The Brigham and Women's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: Shalendar Bhasin, MD    617-525-9150    sbhasin@partners.org   
Contact: Catherine Ghattas    617-525-9198    CGHATTAS@BWH.HARVARD.EDU   
Sponsors and Collaborators
Metro International Biotech, LLC
Investigators
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Principal Investigator: Shalender Bhasin, MD Brigham and Women's Hospital
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Responsible Party: Shalender Bhasin, Principal Investigator, Metro International Biotech, LLC
ClinicalTrials.gov Identifier: NCT05038488    
Other Study ID Numbers: MIB-626-202
First Posted: September 9, 2021    Key Record Dates
Last Update Posted: December 1, 2021
Last Verified: November 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Individual participant data will not be shared

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Shalender Bhasin, Metro International Biotech, LLC:
MIB-626
Covid19
Early Acute Kidney Injury
NAD-boosting drug
Additional relevant MeSH terms:
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COVID-19
Acute Kidney Injury
Respiratory Tract Infections
Infections
Pneumonia, Viral
Pneumonia
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases
Renal Insufficiency
Kidney Diseases
Urologic Diseases