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

NCT04952805 | Unknown Phase 2 DMC

• 1 other identifier: A0001B
• Study Type: interventional
• Target: 800
• Locations: 1 country
• Sites: 14

Brief 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. 1.Select one dose level for progression to Stage-2 Stage-1 + Stage-2 (Phase III)
2. 2.Provide confirmatory evidence of safety and efficacy for regulatory approval.

Conditions

Covid19

Outcome Measures

Primary Outcomes (2)

• Severe (Grade 3) unsolicited AEs and/or serious unsolicited AEs (SAEs).

  Proportion of participants with severe (Grade 3) unsolicited AEs and/or serious unsolicited AEs (SAEs).

  From admission to discharge - Assessed as day 0

• Time to SARS-CoV-2 clearance in the URT.

  Evaluation of the time required for the elimination of SARS-CoV-2 in the URT.

  From baseline (visit 1) up to day 168 ± 7 (visit 12)

Secondary Outcomes (17)

• Unsolicited AEs, including clinically relevant laboratory and ECG abnormalities.

  From baseline (visit 1) up to day 168 ± 7 (visit 12)

• Solicited local AEs at the injection site

  From baseline (visit 1) up to day 28 (Visit 10)

• Number of participants who develop ADA.

  At baseline (visit 1), at day 7 (visit 4), at day 28 (visit 10), at day 56 ± 7 (visit 11) and at day 168 ± 7 (visit 12)

• SARS-CoV-2 clearance in the URT

  At baseline (visit 1), at day 7 (visit 4), at day 28 (visit 10), at day 56 ± 7 (visit 11) and at day 168 ± 7 (visit 12)

• SARS-CoV-2 viral load in nasopharyngeal swab

  From baseline (visit 1) up to day 168 ± 7 (visit 12)

Study Arms (3)

Interventional Arm _400 mg

EXPERIMENTAL

To all the patients enrolled is admistrated with single dose of MAD0004J08 400 mg.

Drug: MAD0004J08

Interventional Arm _100 mg

EXPERIMENTAL

To all the patients enrolled is admistrated with single dose of MAD0004J08 100 mg.

Drug: MAD0004J08

Placebo Arm

PLACEBO COMPARATOR

To all the patients enrolled is admistrated with single dose of placebo

Other: Placebo

Interventions

MAD0004J08 DRUG

MAD0004J08 is a human monoclonal Antibody (mAb), 2.5 mL 2R vial available in two dose: 100 mg and 400 mg. The pharmaceutical form is solution for intramuscular injection.

Interventional Arm _100 mg; Interventional Arm _400 mg

Placebo OTHER

Placebo matching to MAD0004J08, 2.5 mL 2R vial. The pharmaceutical form is solution for intramuscular injection.

Placebo Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Toscana Life Sciences Sviluppo s.r.l.: lead

Study Sites (14)

IRCCS INMI Lazzaro Spallanzani - Istituto nazionale Malattie Infettive

Roma, RM, 00149, Italy

Location

Az. Ospedaliera San Giuseppe Moscati

Avellino, 83100, Italy

Location

Azienda Ospedaliero-Universitaria Careggi di Firenze

Florence, 50134, Italy

Location

A.O. Ospedali Riuniti di Foggia - Università degli Studi di Fog

Foggia, Italy

Location

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano

Milan, 20122, Italy

Location

Az. Ospedaliera dei Colli - P.O. "D. Cotugno"

Napoli, 80131, Italy

Location

Azienda Ospedaliero-Universitaria di Parma

Parma, 43126, Italy

Location

Fondazione IRCCS Policlinico San Matteo di Pavia

Pavia, 27100, Italy

Location

Azienda USL Ospedale "Guglielmo da Saliceto"

Piacenza, 29121, Italy

Location

A.O.U. Pisana - Ospedale di Cisanello

Pisa, 56124, Italy

Location

Policlinico Santa Maria alle Scotte - Università di Siena

Siena, 53100, Italy

Location

Ospedale di Cattinara

Trieste, 34149, Italy

Location

ASL di Vercelli - Ospedale Sant'Andrea

Vercelli, 13100, Italy

Location

A.O.U. Integrata di Verona

Verona, 37134, Italy

Location

Related Publications (1)

• Kreuzberger N, Hirsch C, Chai KL, Tomlinson E, Khosravi Z, Popp M, Neidhardt M, Piechotta V, Salomon S, Valk SJ, Monsef I, Schmaderer C, Wood EM, So-Osman C, Roberts DJ, McQuilten Z, Estcourt LJ, Skoetz N. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;9(9):CD013825. doi: 10.1002/14651858.CD013825.pub2.

  PMID: 34473343 DERIVED

MeSH Terms

Conditions

COVID-19

Interventions

MAD0004J08

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Simone Lanini

  IRCCS INMI Lazzaro Spallanzani - Istituto nazionale Malattie Infettive

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 1, 2021
• First Posted: July 7, 2021
• Study Start: June 6, 2021
• Primary Completion: March 31, 2022
• Study Completion: August 31, 2022
• Last Updated: February 3, 2022

Record last verified: 2022-02

Locations

IT (14)