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

Phase 2

Completed

Conditions: Covid19
Stage 1 Acute Kidney Injury

Interventions: Drug: MIB-626
Drug: Placebo
Other: Home Treatment

Registration Number: NCT05038488

Lead Sponsor: 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.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 42

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
MIB-626	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.
Placebo Tablet	Placebo	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.
Home Treatment	MIB-626	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.
Home Treatment	Placebo	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.
Home Treatment	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

Name	Time	Method
Change from baseline in serum cystatin C levels	enrollment to 14 days or hospital discharge, or death, whichever comes first	Change from baseline in serum cystatin C levels

Secondary Outcome Measures

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