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

Covid19 Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05038488
• Other study ID #: MIB-626-202
• Status: Completed
• Phase: Phase 2
• Start date: October 26, 2021
• Est. completion date: August 17, 2023

Study information

• Verified date: March 2024
• Source: Metro International Biotech, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: August 17, 2023
• Est. primary completion date: August 17, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acute Kidney Injury
• COVID-19
• Covid19

Intervention

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.
• 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.

Locations

Country	Name	City	State
United States	The Brigham and Women's Hospital	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Metro International Biotech, LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Other	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
Other	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
Other	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
Other	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
Other	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
Other	The length of hospital stay	The length of hospital stay	enrollment to 14 days or hospital discharge, or death, whichever comes first
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Change from baseline in oxygen saturation	Change from baseline in oxygen saturation	enrollment to 14 days or hospital discharge, or death, whichever comes first
Secondary	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
Secondary	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
Secondary	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