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

February 2, 2022 updated by: Toscana Life Sciences Sviluppo s.r.l.

Randomized, Placebo-controlled, Double-blind, Multicenter, Seamless Adaptive Phase II-III Clinical Trial to Select the Dose and Evaluate Safety and Efficacy of MAD0004J08 Monoclonal Antibody in Adult Patients With Recently Diagnosed Asymptomatic to Moderately Severe COVID-19

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This clinical trial is designed as a randomized, stratified, placebo-controlled doubleblind, multicenter, seamless adaptive study. The target study population is adult patients ≥ 18 years of age with recently diagnosed (≤ 3 days from 1st positive swab taken) asymptomatic to moderately severe COVID-19 at baseline. Patients with comorbidities will be allowed in the study assuming all inclusion and exclusion criteria are met. Participants will not require hospitalization at baseline.

The trial is designed in two stages:

  • Stage I: participants will be randomized (1:1:1 ratio) to one of the one of the following three study cohorts:
  • MAD0004J08 400 mg, single dose
  • MAD0004J08 100 mg, single dose
  • Placebo, single dose The collected data will be analysed following a pre-planned interim analysis plan. Based on the results of this analysis the Data Monitoring Committee (DMC) will recommend whether the study should advance to Stage-2, and if so, will recommend selection of one of the two MAD0004J08 treatments for Stage-2. Alternatively, the DMC will recommend stopping the study. Final decisions will be made by an unblinded sub-group of the Steering Committee (SC), including senior Sponsor representatives, based on summary results.
  • Stage-2: participants will be randomized (1:1 ratio) to one of two treatments:
  • MAD0004J08, dose level selected in Stage-1, single dose
  • Placebo, single dose Twelve (12) study visits and 2 telephone calls are scheduled for each participant over approximately 168 days. Additional ad-hoc visit(s) may be necessary to confirm eradication of SARS-CoV-2 from the upper respiratory tract (URT) following the 1st negative swab.

At Visit 1 (baseline) all participants will undergo testing for serum IgA and IgG vs. the spike (S) protein, and IgG vs. nucleocapsid (N) protein: participants testing negative to all three antibodies at baseline are referred to as seronegative; participants testing positive to any of the three antibodies at baseline are referred to as seropositive. Due to the need to minimize time between diagnosis and intervention, screening procedures, baseline procedures, randomization and administration of study treatment will occur on day 1.

Visits from Day 3 to Day 21 (Visits 2 to 9) will be conducted by study staff at the participant's home, unless the participant is hospitalized. Visits from Day 28 to Day 168 (Visits 10 to 12) will be conducted at the study center. Participants requiring hospitalization during the study period are to be hospitalized at the study center where Visit 1 was conducted.

At each scheduled visit nasopharyngeal swabs will be carried out. Additional swabs may be taken ad hoc to confirm eradication after the 1st negative swab.

Safety and efficacy endpoints will be analyzed as appropriate in two target populations (all randomized participants (ALL) and seronegative randomized participants (SEROneg) and three time-windows ( baseline (Visit 1) to end of Stage-1 or dropout (interim analysis), baseline (Visit 1) to end of Stage-2 or dropout (primary analysis) and baseline (Visit 1) to end of study (Visit 12) or dropout (final analysis).

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
800

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Avellino, Italy, 83100
        • Az. Ospedaliera San Giuseppe Moscati
      • Firenze, Italy, 50134
        • Azienda Ospedaliero-Universitaria Careggi di Firenze
      • Foggia, Italy
        • A.O. Ospedali Riuniti di Foggia - Università degli Studi di Fog
      • Milano, Italy, 20122
        • Fondazione Irccs Ca' Granda Ospedale Maggiore Policlinico Di Milano
      • Napoli, Italy, 80131
        • Az. Ospedaliera dei Colli - P.O. "D. Cotugno"
      • Parma, Italy, 43126
        • Azienda Ospedaliero-Universitaria di Parma
      • Pavia, Italy, 27100
        • Fondazione IRCCS Policlinico San Matteo di Pavia
      • Piacenza, Italy, 29121
        • Azienda USL Ospedale "Guglielmo da Saliceto"
      • Pisa, Italy, 56124
        • A.O.U. Pisana - Ospedale di Cisanello
      • Siena, Italy, 53100
        • Policlinico Santa Maria alle Scotte - Università di Siena
      • Trieste, Italy, 34149
        • Ospedale di Cattinara
      • Vercelli, Italy, 13100
        • ASL di Vercelli - Ospedale Sant'Andrea
      • Verona, Italy, 37134
        • A.O.U. Integrata di Verona
    • RM
      • Roma, RM, Italy, 00149
        • IRCCS INMI Lazzaro Spallanzani - Istituto nazionale Malattie Infettive

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Interventional Arm _400 mg
To all the patients enrolled is admistrated with single dose of MAD0004J08 400 mg.
Drug: MAD0004J08
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.
Experimental: Interventional Arm _100 mg
To all the patients enrolled is admistrated with single dose of MAD0004J08 100 mg.
Drug: MAD0004J08
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.
Placebo Comparator: Placebo Arm
To all the patients enrolled is admistrated with single dose of placebo
Other: Placebo
Placebo matching to MAD0004J08, 2.5 mL 2R vial. The pharmaceutical form is solution for intramuscular injection.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Severe (Grade 3) unsolicited AEs and/or serious unsolicited AEs (SAEs).
Time Frame: From admission to discharge - Assessed as day 0
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.
Time Frame: From baseline (visit 1) up to day 168 ± 7 (visit 12)
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Unsolicited AEs, including clinically relevant laboratory and ECG abnormalities.
Time Frame: From baseline (visit 1) up to day 168 ± 7 (visit 12)
Proportion of participants with 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
Time Frame: From baseline (visit 1) up to day 28 (Visit 10)
Proportion of participants with solicited local AEs at the injection site. Will be considered: pain, swelling and redness at the injection site.
From baseline (visit 1) up to day 28 (Visit 10)
Number of participants who develop ADA.
Time Frame: 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)
Proportion of participants who develop ADA. The first 60 randomized participants will be tested for 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
Time Frame: 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)
Proportion of participants with SARS-CoV-2 clearance in the Upper Respiratory Tract (URT) at each visit.
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
Time Frame: From baseline (visit 1) up to day 168 ± 7 (visit 12)
SARS-CoV-2 viral load (number of copies) in nasopharyngeal swab, as measured by RT-PCR at each visit.
From baseline (visit 1) up to day 168 ± 7 (visit 12)
SPO2% and lowest SpO2 % post baseline.
Time Frame: From baseline (visit 1) up to day 168 ± 7 (visit 12)
SPO2 % value at each visit and lower SpO2 % after baseline.
From baseline (visit 1) up to day 168 ± 7 (visit 12)
SpO2 % < 94%.
Time Frame: From baseline (visit 1) up to day 168 ± 7 (visit 12)
Proportion of participants with SpO2 % < 94%.
From baseline (visit 1) up to day 168 ± 7 (visit 12)
Participants with increased dose home oxygen therapy
Time Frame: From baseline (visit 1) up to day 168 ± 7 (visit 12)
Proportion of participants with newly established or increased dose home oxygen therapy increased home oxygen therapy (only applies to patients with underlying conditions other than COVID-19 requiring such therapy, e.g., COPD).
From baseline (visit 1) up to day 168 ± 7 (visit 12)
Area under the curve (AUC) of COVID-19 total symptom score (range: 0-24).
Time Frame: From baseline (visit 1) up to day 168 ± 7 (visit 12)
Assessment of COVID-19 total symptom score
From baseline (visit 1) up to day 168 ± 7 (visit 12)
Participants requiring hospitalization
Time Frame: From event start (day 0) through event completion
Proportion of participants requiring hospitalization.
From event start (day 0) through event completion
Cumulative time of hospital stay in days.
Time Frame: From event start (day 0) through event completion
Number of days the participant was hospitalised
From event start (day 0) through event completion
Hospitalized participants requiring supplemental oxygen therapy.
Time Frame: From event start (day 0) through event completion
Proportion of hospitalized participants requiring supplemental oxygen therapy.
From event start (day 0) through event completion
Cumulative time of hospitalized oxygen therapy in days.
Time Frame: From event start (day 0) through event completion
Number of days the hospitalized participant required oxygen therapy
From event start (day 0) through event completion
Participants admitted to intensive care unit (ICU).
Time Frame: From event start (day 0) through event completion
Proportion of participants admitted to intensive care unit (ICU).
From event start (day 0) through event completion
Cumulative time of ICU stay in days.
Time Frame: From event start (day 0) through event completion
Number of days the hospitalized participant stay in therapy intensive care unit
From event start (day 0) through event completion
All-cause mortality.
Time Frame: From baseline (visit 1) to through study completion
Analysis of all All-cause mortality.
From baseline (visit 1) to through study completion
MAD0004J08 serum concentration.
Time Frame: From baseline (visit 1) up to day 168 ± 7 (visit 12)
Evaluation of MAD0004J08 serum concetration
From baseline (visit 1) up to day 168 ± 7 (visit 12)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Toscana Life Sciences Sviluppo s.r.l.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Simone Lanini, IRCCS INMI Lazzaro Spallanzani - Istituto nazionale Malattie Infettive

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 6, 2021

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 31, 2022

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 31, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 1, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 5, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 7, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 3, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 2, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • A0001B

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

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