Study to Select the Dose and Evaluate Safety and Efficacy of Monoclonal Antibody in Adult With Recently Diagnosed Asymptomatic to Moderately Severe COVID-19.

• Status: Recruiting
• Trial end date: 2022-08-31
• Target enrollment: 0
• Participant gender: All

Summary

MAD0004J08, the experimental drug, is a potent neutralizing IgG1 monoclonal antibody (mAb) targeting the spike protein of SARS-CoV-2. MAD0004J08 blocks viral attachment and entry into human cells and neutralizes the virus. Because of its high affinity and potency, MAD0004J08 may accelerate clearance of the virus and prevent clinical deterioration of COVID-19 patients, especially when administered shortly after infection, and prevent SARS-CoV-2 infection in uninfected subjects. Because of its high potency, MAD0004J08 is expected to be effective at low doses (mg range) and thus will be administered by intramuscular (IM) injection, as opposed to the intravenous bolus required by high dose mAbs.

The goals of this Phase II-III seamless adaptive clinical trial are:

Stage-1 (Phase II)

1. Select one dose level for progression to Stage-2 Stage-1 + Stage-2 (Phase III)

2. Provide confirmatory evidence of safety and efficacy for regulatory approval.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Toscana Life Sciences Sviluppo s.r.l.

Criteria

Inclusion Criteria:

• Signed written informed consent taken before any study procedure from any patient capable of giving consent, or, when the patient is incapable of doing so, by his or her legal/authorized representative.

• Age ≥18 years. At least 30% of participants will be ≥ 65 years old.

• First nasopharyngeal swab testing positive for SARS-CoV-2 by RT-PCR taken no more than 3 days before randomization (Visit 1). Results of "rapid" semiquantitative tests are not acceptable.

• Asymptomatic to moderately symptomatic outpatients with no need for immediate hospitalization: grade 1, or grade 2 or grade 3 of Clinical Severity Scale.

• No childbearing potential (post-menopause, surgically-induced, or pharmacologically-induced sterility) or, if of childbearing potential, negative urinary pregnancy test (women) and commitment to use at least 2 forms of contraception for at least 168 days from administration of study drug (men and women).

Exclusion Criteria:

• Severe or critical COVID-19: grade 4 or grade 5 of clinical severity scale.

• Current hospitalization and/or hospitalization or emergency room visit in the past 14 days.

• Need for immediate hospitalization for any reason in the investigator's opinion.

• Severe liver disease as determined by values of ALT and/or AST >5x upper limit of normal (ULN) and/or history of liver cirrhosis.

• Severe renal disease as determined by estimated creatinine clearance (CcCl) <30 mL/min or serum creatinine >2 mg/dL (>176.8 μmol/L) or ongoing renal dialysis.

• Absolute neutrophil count (ANC) < 1000/μL.

• Demyelinating and connective tissue disease.

• Active tuberculosis or suspected active bacterial, fungal, viral, or other infection (besides COVID- 19).

• Any condition that in the Investigator's opinion may be negatively affected by the study treatments and/or study procedures.

• Any condition, including psychiatric disorders, alcohol, or substance abuse, which in the Investigator's opinion may interfere with completion of the study procedures.

• Any condition with life expectancy <6 months in the Investigator's opinion.

• Ongoing or planned pregnancy.

• Ongoing breast feeding.

• History of life-threatening event in the 1 month before Visit 1.

• History of surgery in the 1 month before Visit 1.

• History of treatment with blood components in the 6 months before Visit 1.

• History of cancer treated with chemotherapy in the 6 months before Visit 1.

• History of solid organ transplant at any time before Visit 1.

• History of severe and/or serious allergic reaction to monoclonal antibodies or any component of MAD0004J08, including anaphylaxis at any time before Visit 1.

• Treatment with an investigational drug or vaccine within 5 half-lives or 30 days (whichever is longer) of randomization.

• Treatment at any time with monoclonal antibodies bamlanivimab, bamlanivimab + etesevimab combination, and casiribimab + imdevimab combination.