Safety and Antiviral Activity of BLD-2660 in COVID-19 Hospitalized Subjects
Condition: Sars-CoV-2; Covid19
MeSH terms: COVID-19
Intervention: BLD-2660
Intervention description: BLD-2660 is a novel, synthetic, orally active, small molecule inhibitor of calpain (CAPN) 1, 2, and 9.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 120.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      BLD-2660 is a novel, synthetic, orally active, small molecule inhibitor of calpain (CAPN) 1,
      2, and 9 that is selective over the cathepsins as well as other protease families, displays
      good metabolic stability and permeability, oral bioavailability and low cytochrome P450 (CYP)
      inhibition. It is under development for the treatment of coronavirus disease-19 (COVID-19)
      resulting from infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARSCoV2),
      where there is significant unmet medical need.
    

Eligibility criteria:

        Inclusion Criteria:

        At least 18 years of age at the time of signing the ICF.

        Hospitalized for COVID-19.

        Diagnosed with COVID-19 as defined by having at least 2 of the following signs or symptoms
        within the past 2 days:

          -  Fever defined as a body temperature of ≥ 38.0 °C oral, or ≥ 38.3 °C rectal, ≥37.7 °C
             forehead or ≥38.7°C aural (axillary temperatures are not allowable);

          -  Cough;

          -  Fatigue;

          -  Shortness of breath.

        Radiographic evidence (chest x-ray or CT scan) of one the following:

          -  Ground-glass opacities, or

          -  Local or bilateral patchy infiltrates, or

          -  Interstitial pulmonary infiltrates.

        Oxygen requirements:

          -  SpO2 ≤ 94% on ambient air OR

          -  Requires supplemental oxygen administration by nasal cannula, simple face mask, or
             other similar oxygen delivery device.

        Male and/or female subjects.

        - Contraception use by men or women should be consistent with local regulations regarding
        the methods of contraception for those participating in clinical studies.

        All subjects (male or female) who are of childbearing potential must agree to use highly
        effective contraception during the study. Female subjects and male partners of female
        subjects must continue to use highly effective contraception for 30 days after the last
        dose of study drug. Female subjects should not donate oocytes during this time. Male
        subjects and female partners of male subjects must continue to use highly effective
        contraception for 90 days. Male subjects must agree not to donate sperm during this time.

        Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception
        for the subject.

        Note: Ethinyl estradiol is the primary estrogen used in hormonal contraceptives. The
        progestin component consists of norethindrone, levonorgestrel, norgestrel, norethindrone
        acetate, ethynodiol diacetate, norgestimate, desogestrel, and drospirenone. As BLD-2660 is
        a weak CYP3A4 inducer, exposure to both the estrogen and progestin components in hormonal
        contraceptives may be decreased, resulting in an increased risk of pregnancy. As such, it
        is recommended that subjects who are on hormonal contraceptives for birth control should
        use an alternate means of contraception (condoms, diaphragms, intrauterine device (IUD),
        other barrier methods, sexual abstinence, etc.) during participation in the study.

        Women of childbearing potential must have a negative serum pregnancy test at Screening
        within 72 hours prior to first administration of study drug.

        Women not of childbearing potential must be postmenopausal (defined as cessation of regular
        menstrual periods for at least 1 year

        Capable of giving signed informed consent which includes compliance with the requirements
        and restrictions listed in the ICF and in this protocol

        Exclusion Criteria:

        Active bacterial pneumonia infection

        Known active tuberculosis (TB).

        History of Child-Pugh B or C cirrhosis.

        History of ischemic heart disease or myocardial infarction or acute coronary syndrome.

        Subjects requiring supplemental oxygen ≥0.75 FiO2.

        It is not in the best interest of the subjects to participate, in the opinion of the
        treating Investigator.

        Female subjects who are pregnant or breastfeeding or expecting to conceive within the
        projected duration of the study, starting with the screening visit through 90 days after
        the last dose of study drug.

        The following laboratory parameters are excluded:

          -  Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >5 x upper limit of
             normal (ULN);

          -  Creatinine clearance < 50 mL/min.

        Requiring, or expected to require mechanical ventilation at screening.

        Treatment with chloroquine or hydroxychloroquine at study entry.

        Treatment with anti-IL 6, anti-IL-6 receptor antagonists, or with Janus kinase inhibitors
        (JAKi) in the past 30 days or plans to receive during the study period.

        Participation in any other clinical study of an experimental drug treatment for COVID-19
        within 6 half-lives of the experimental treatment.

        Note: Subjects participating in an observational study are an exception to this criterion
        and may qualify for the study with Sponsor approval.

        Note: Subjects who have entered the follow-up phase of an investigational study may
        participate as long as it has been 4 weeks after the last dose of the previous
        investigational agent.

          -  Unable to swallow solid oral medication or known malabsorption disorder.

          -  Subjects who have allergy to BLD-2660 or inactive components of BLD-2660.