Clinical trial NCT05038488: Phase 2a MIB-626 vs. Placebo COVID-19
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Covid19
Stage 1 Acute Kidney Injury
Keywords: MIB-626
Covid19
Early Acute Kidney Injury
NAD-boosting drug
Lead sponsor: Metro International Biotech, LLC
Sponsor class: INDUSTRY
First posted: 2021-09-09
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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.

Eligibility 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.

Primary outcomes:
measure: Change from baseline in serum cystatin C levels
timeFrame: enrollment to 14 days or hospital discharge, or death, whichever comes first
Secondary outcomes:
measure: Change from baseline to peak concentrations of inflammatory biomarkers (IL6, TNF-alpha, hsCRP, Angiotensin 2 to Angiotensin1, 7 ratio, ACE 2)
timeFrame: enrollment to 14 days or hospital discharge, or death, whichever comes first
measure: The trajectory of change from baseline in concentrations of inflammatory biomarkers (IL6, TNF-alpha, hsCRP, Angiotensin 2 to Angiotensin1, 7 ratio, ACE 2)
timeFrame: enrollment to 14 days or hospital discharge, or death, whichever comes first
measure: Change from baseline in markers of endothelial damage (vWF, VCAM, PAI-1)
timeFrame: enrollment to 14 days or hospital discharge, or death, whichever comes first
measure: Change from baseline in markers of microvascular thrombosis (D-dimer, fibrinogen)
timeFrame: enrollment to 14 days or hospital discharge, or death, whichever comes first
measure: The trajectory of change in plasma (NGAL, KIM-1) and urinary (KIM-1, NGAL, albumin) biomarkers of acute kidney injury
timeFrame: enrollment to 14 days or hospital discharge, or death, whichever comes first
measure: Change in urinary albumin concentration (normalized to urine creatinine) from enrollment to peak during hospitalization
timeFrame: enrollment to 14 days or hospital discharge, or death, whichever comes first
measure: Change from baseline in oxygen saturation
timeFrame: enrollment to 14 days or hospital discharge, or death, whichever comes first
measure: Change in high sensitivity troponin-1 concentration from enrollment to peak during hospitalization (measured daily in stored biospecimens)
timeFrame: enrollment to 14 days or hospital discharge, or death, whichever comes first
measure: Change from baseline in intracellular NAD+ concentrations in blood during the 14-day treatment period in a subset of study participants
timeFrame: enrollment to 14 days or hospital discharge, or death, whichever comes first
measure: Circulating concentrations of MIB-626 and its key metabolites P2Y, NAAD, NAM, 1-methylnicotinamide during the 14-day treatment period
timeFrame: enrollment to 14 days or hospital discharge, or death, whichever comes first
Other outcomes:
measure: Progression in the stage of acute kidney injury increase in serum creatinine OR serum creatinine > 4.0 mg/dL OR need
timeFrame: enrollment to 14 days or hospital discharge, or death, whichever comes first
measure: The WHO 8-point Ordinal Scale of Clinical Status
timeFrame: enrollment to 14 days or hospital discharge, or death, whichever comes first
measure: Change from baseline in Modified Sequential Organ Failure Assessment (SOFA) Score (SOFA) Score
timeFrame: enrollment to 14 days or hospital discharge, or death, whichever comes first
measure: The number and proportion of patients requiring mechanical ventilation, hemodialysis, or transferred to ICU
timeFrame: enrollment to 14 days or hospital discharge, or death, whichever comes first
measure: The number and proportion of patients requiring hemodialysis
timeFrame: enrollment to 14 days or hospital discharge, or death, whichever comes first
measure: The number and proportion of patients who die
timeFrame: enrollment to 14 days or hospital discharge, or death, whichever comes first
measure: The number of days it takes for the temperature to return to normal (<99F)
timeFrame: enrollment to 14 days or hospital discharge, or death, whichever comes first
measure: The length of hospital stay
timeFrame: enrollment to 14 days or hospital discharge, or death, whichever comes first
Locations:
city: Boston
country: United States
facility: The Brigham and Women's Hospital
state: Massachusetts
Study officials:
affiliation: Brigham and Women's Hospital
name: Shalender Bhasin, MD
role: PRINCIPAL_INVESTIGATOR
References: