A Study of LAM-002A for the Prevention of Progression of COVID-19
Condition: COVID-19 Disease
MeSH terms: COVID-19
Intervention: Apilimod Dimesylate Capsule; Placebo
Intervention description: LAM-002A is formulated in capsules containing 25 mg of apilimod dimesylate. The capsule is Swedish orange, Size 0.; Microcrystalline cellulose in Swedish orange, Size 0 capsules
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description: Double-blinded
Enrollment: 142.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: COVID-19; SARS-CoV-2; Apilimod Dimesylate; LAM-002A; Coronavirus; AI Therapeutics

Summary:

      This is a clinical trial to evaluate the efficacy of LAM-002A compared to placebo treatment
      in adults with a confirmed SARS-CoV-2 infection who are receiving standards supportive care
      in an outpatient setting.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Written documentation of SARS-CoV-2 infection confirmed by a validated test.

          2. Presence of greater than or equal to ≥1 of the following COVID-19-related symptoms
             indicating mild disease: fever (temperature ≥100.4), anosmia (loss of taste or smell),
             cough, sore throat, gastrointestinal complaints (e.g. nausea, vomiting, or diarrhea),
             chills, congestion, or runny nose, headaches, muscle or body aches, fatigue, or
             asymptomatic patients who have tested positive for COVID-19 via a validated test
             within the past 4 days.

          3. If symptomatic, symptom onset less than or equal to ≤ 8 days.

          4. For female participants of childbearing potential, a negative urine (or serum)
             pregnancy test.

          5. For female participants of childbearing potential, willingness to use a
             protocol-recommended method of contraception from the start of the screening period
             until greater than or equal to ≥30 days after the final dose of study therapy. Note: A
             female subject is considered to be of childbearing potential unless she has had a
             hysterectomy, bilateral tubal ligation, or bilateral oophorectomy; has medically
             documented ovarian failure (with serum estradiol and follicle-stimulating hormone
             [FSH] levels within the institutional laboratory postmenopausal range and a negative
             serum or urine beta human chorionic gonadotropin [βHCG]); or is menopausal (age ≥50
             years with amenorrhea for ≥6 months).

          6. For male participants who can father a child and are having intercourse with females
             of childbearing potential who are not using adequate contraception, willingness to use
             a protocol-recommended method of contraception from the start of study therapy until
             ≥30 days after the final dose of study therapy and to refrain from sperm donation from
             the start of study therapy until ≥90 days after administration of the final dose of
             study therapy. Note: A male subject is considered able to father a child unless he has
             had a bilateral vasectomy with documented aspermia or a bilateral orchiectomy.

          7. Willingness and ability of the participant to ingest study drug capsules.

          8. Willingness of the participant to comply with scheduled visits, drug administration
             plan, protocol-specified laboratory tests, study procedures, and study restrictions.

          9. Evidence of a personally signed informed consent indicating that the participant is
             aware of the nature of the disease and has been informed of the procedures to be
             followed, the experimental nature of the therapy, alternatives, potential risks and
             discomforts, potential benefits, and other pertinent aspects of study participation.

        Exclusion Criteria:

          1. Respiratory rate greater than or equal to ≥20 breaths per minute.

          2. Oxygen saturation by pulse oximetry less than or equal to ≤93 percent % on room air or
             requirement for supplemental oxygen to maintain oxygen saturation greater than >93
             percent %.

          3. Total NEWS score greater than or equal to ≥6 or presence of a score of 3 on any of the
             individual NEWS parameters.

          4. Radiographic evidence of pulmonary infiltrates (clinical X-ray within 2 days of
             referral)

          5. Hepatic profile showing any of the following:

               -  Serum alanine aminotransferase (ALT) greater than >5 × upper limit of normal
                  (ULN) (CTCAE Grade greater than or equal to ≥3).

               -  Serum aspartate aminotransferase (AST) greater than >5 × ULN (CTCAE Grade greater
                  than or equal to ≥3).

               -  Serum bilirubin greater than >1.5 × ULN (CTCAE Grade greater than or equal to
                  ≥2).

          6. Renal profile showing an estimated creatinine clearance (eClCR) less than <30
             mL/minute (with eClCR to be calculated by the method at the laboratory performing the
             serum creatinine test).

          7. Presence of a cancer with disease manifestations or therapy that could adversely
             affect subject safety or longevity, create the potential for drug-drug interactions,
             or compromise the interpretation of study results.

          8. Significant cardiovascular disease (e.g. myocardial infarction, arterial
             thromboembolism, cerebrovascular thromboembolism) within 1 month prior to start of
             study therapy; unstable angina; symptomatic peripheral vascular disease; CTCAE Grade
             greater than or equal to ≥2 congestive heart failure; or uncontrolled CTCAE Grade
             greater than or equal to ≥3 hypertension (diastolic blood pressure greater than or
             equal to ≥100 mmHg or systolic blood pressure greater than or equal to ≥160 mmHg)
             despite antihypertensive therapy.

          9. Significant screening ECG abnormalities, including atrial fibrillation/flutter, 2nd
             degree atrioventricular (AV) block type II, 3rd-degree AV block, Grade greater than or
             equal to ≥2 bradycardia, or corrected QT (QTc by Fridericia [QTcF]) greater than >480
             msec (Grade greater than >1).

         10. Gastrointestinal disease (e.g. gastric or intestinal bypass surgery, pancreatic enzyme
             insufficiency, malabsorption syndrome, symptomatic inflammatory bowel disease, chronic
             diarrheal illness, bowel obstruction) that might interfere with drug absorption or
             with interpretation of gastrointestinal AEs.

         11. Pregnancy or breastfeeding.

         12. Prior solid organ transplantation.

         13. Use within 5 days prior to randomization of an approved or investigational therapy
             intended to treat COVID-19 (e.g. remdesivir, , anti-interleukin [IL]-6 antibodies,
             therapeutic anti-SARS CoV-2 antibodies or post-convalescent plasma, anti- SARS CoV-2
             vaccine, Bruton tyrosine kinase [BTK] inhibitor), use within 3 months of chloroquine
             or hydroxychloroquine. Note: participants are not precluded from undergoing
             evaluations involving observation, noninvasive diagnostic procedures or sampling, or
             questionnaires as follow-up to a prior study or as components of a concurrent
             noninterventional study.

         14. Use within 5 days prior to randomization of a strong inhibitor or inducer of
             cytochrome P450 (CYP) 3A4 or expected requirement for chronic use of a strong
             inhibitor or inducer of CYP3A4 during study therapy.

         15. Use within 5 days prior to randomization of drug that is a moderate-to-strong
             substrate of CYP2C9 (including warfarin, tolbutamide, phenytoin, glimepiride) or
             expected requirement for chronic use of such drugs during study therapy.

         16. Use within 5 days prior to randomization of a drug known to prolong the QT interval

         17. Ongoing immunosuppressive therapy including systemic or enteric corticosteroids.
             (Note: At study entry, participants may be using intraarticular, inhaled, or topical
             corticosteroids. During study therapy, participants may use systemic, enteric,
             intraarticular, inhaled, or topical corticosteroids as required for intercurrent
             conditions.)

         18. Any illness, medical condition, organ system dysfunction, or social situation,
             including mental illness or substance abuse, deemed by the investigator to be likely
             to interfere with a participant's ability to provide informed consent, adversely
             affect the participant's ability to cooperate and participate in the study, or
             compromise the interpretation of study results.