Study to Evaluate the Safety and Concentrations of Monoclonal Antibody Against Virus That Causes COVID-19 Disease.

NCT04932850 | Completed Phase 1 DMC

• 2 other identifiers: A0001A2020-005469-15
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

Brief Summary

A Phase I dose-escalation study to test a new monoclonal antibody (called MAD0004J08) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19 disease. The study aims to evaluate the safety and pharmacokinetics (distribution and elimination) of anti-SARSCoV-2 monoclonal antibody in healthy adults. The primary objective of the study is to evaluate the safety of anti-SARSCoV-2 monoclonal antibody (that is the appearance of adverse events), the pharmacokinetics (how MAD0004J08 is distributed and eliminated by human body), the generation of anti-drug antibodies (ADAs) (that is the possible production of antibodies against the drug, which could invalidate it efficacy) and finally the ability of MAD0004J08 to neutralize SARSCoV-2. Furthermore a blood sample would be used to evaluate a kit (DIESSE kit), developed by Toscana Life Sciences, able to detect the administered drug. This kit is not used to evaluate study paramethers. 30 subjects, that should respect the Inclusion/Exclusion criteria, will be enrolled. About 12 visits will be performed during the study, study duration will be about 6 months. Subjects will be distributed into 3 Cohorts, each of them divided into 2 groups that would receive MAD0004J08 (Dose 1 = 48 mg, Dose 2 = 100 mg or Dose 3 = 400 mg) or placebo. Administration occurs as intramuscular injection (single injection for Cohort 1 and Cohort 2 and, two injections for Cohort 3) .

Conditions

COVID-19 Virus Disease

Keywords

COVID-19 Pandemic; SARS-CoV-2 Infection; SARS-CoV-2 Monoclonal Antibody

Outcome Measures

Primary Outcomes (1)

• Severe/serious treatment-emergent adverse events

  Proportion of subjects with severe / serious treatment-emergent adverse events (TEAEs) (including clinically relevant laboratory abnormalities, vital signs, and adverse reactions at the injection site) in the 7 days post-treatment.

  From Day 1 to Day 8

Secondary Outcomes (11)

• Unsolicited and solicited TEAE

  From Day 1 to Day 180

• Peak Plasma Concentration (Cmax)

  At each visit from Day 1 to Day 180

• Area under the concentration-time curve from time zero to time t (AUC0-t)

  At each visit from Day 1 to Day 180

• Area under the concentration vs. time curve up to infinity (AUC0-∞)

  At each visit from Day 1 to Day 180

• Time to achieve Cmax (tmax)

  At each visit from Day 1 to Day 180

Other Outcomes (1)

• ELISA DIESSE kit characterisation

  At Day 1,Day 3, Day 8, Month 1, Month 4 and Month 6.

Study Arms (2)

Active

EXPERIMENTAL

3 active cohorts are involved into study: Cohort 1 (48 mg), Cohort 2 (100 mg) and Cohort 3 (400 mg). Each cohort is composed of two groups. The subjects enrolled in the first group of each cohort (groups 1, 3 and 5 for Cohorts 1, 2 and 3, respectively) will be sentinel subjects and will be treated one at the time at 48 h intervals in order to evaluate possible treatment-related adverse events.

Biological: MAD0004J08

Placebo

PLACEBO COMPARATOR

Placebo will be administered to 2 subjects for each cohort.

Other: Placebo

Interventions

MAD0004J08 BIOLOGICAL

Human mAb 100 mg / 2.5 mL solution for injection

Active

Placebo OTHER

Placebo matching to MAD0004J08 2.5 mL solution for injection

Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Full comprehension: Ability to comprehend the full nature and purpose of the study, including possible risks and side effects; ability to co-operate with the Investigator and to comply with the requirements of the entire study
• Sex and age: Healthy men and women, 18 - 55 years old, inclusive
• Negative SARS-CoV-2 serology test at screening (negative anti-S and anti-N)
• Negative SARS-CoV-2 qRT-PCR in the 72 h before treatment (test on day -3 or -2 or -1 with result before treatment)
• Body Mass Index: 18.5-30 kg/m2, inclusive, at screening
• Vital signs: Systolic blood pressure 90-139 mmHg, diastolic blood pressure 60-90 mmHg, heart rate 50-100 bpm, measured after 5 min at rest in the supine position
• ECG: Electrocardiogram without clinically significant abnormalities at screening
• Contraception and fertility: Women of child-bearing potential must be using at least one of the following reliable methods of contraception and confirm to use adequate contraception during the study:
• Hormonal oral or implantable or transdermal, or injectable contraceptives for at least 2 months before the screening visit;
• A non-hormonal intrauterine device or female condom with spermicide or contraceptive sponge with spermicide or diaphragm with spermicide or cervical cap with spermicide for at least 2 months before the screening visit
• A male sexual partner who agrees to use a male condom with spermicide
• A sterile sexual partner
• A same sex partner Female participants of non-child-bearing potential or in post-menopausal status for at least 1 year will be admitted. For all women, urine pregnancy test result must be negative at screening and day 1

You may not qualify if:

• Physical findings: Clinically significant abnormal physical findings which could interfere with the objectives of the study
• Allergy: Ascertained or presumptive hypersensitivity to the active principle and/or ingredients of the investigational products; history of anaphylaxis to drugs or allergic reactions likely to be exacerbated by any component of the investigational products in the Investigator's opinion
• Concomitant medications: Medications, including over the counter (OTC) medications and herbal remedies, for 2 weeks before screening and immunoglobulin or blood products for 6 months before screening (except contraceptives or a single use of paracetamol, aspirin, or combination OTC products containing paracetamol with an antihistamine, or OTC non-steroidal anti-inflammatory drugs (NSAIDs) at a dose equal or lower than that recommended on the package; vitamins and nutritional supplements, if regularly taken before the study, are also allowed)
• Monoclonal Antibodies (mAb): Previous intake of a mAb within 6 months, or 5 antibody half-life, whichever is longer, before study start
• Transient acute illness: Acute (time-limited) illness, including fever above 37.5°C on the day before or on the day of the planned treatment; subjects excluded for transient acute illness may be dosed if illness resolves within the screening period or may be rescreened once
• Diseases: Significant history of renal, hepatic, gastrointestinal, cardiovascular, respiratory, skin, haematological, endocrine, psychiatric or neurological diseases that may interfere with the aim of the study or increase subjects risks; history of malignancy in the last 5 years
• SARS CoV-2 or COVID-19:
• Participants with any confirmed current or previous COVID-19 infection at screening, or at day -1 or day 1
• Participant with clinical signs or symptoms consistent with COVID-19, e.g. fever, dry cough, dyspnoea, sore throat, fatigue or confirmed infection by appropriate laboratory test within the last 4 weeks before/at screening or at day -1 or day 1
• Any prior intake of investigational or licenced vaccine indicated for the prevention of SARS CoV-2 or COVID-19 or expected intake during follow-up period
• Has been reported as a case (confirmed or probable) of COVID-19 from the regional health system
• Immunodeficiency due to illness, including HIV infection (positivity to anti-HIV-Ab), or due to drugs, including any course of glucocorticoid therapy exceeding 2 weeks of prednisone or equivalent within 6 months before screening.
• Infections: History of active infection with hepatitis B or C or positive test result for anti-HCV-Ab or HBsAg or anti-HBc-Ab at screening; history of infection with SARS or MERS
• Laboratory analyses: Abnormal laboratory values that in the opinion of the Investigator are clinically significant
• Investigative drug studies: Participation in the evaluation of any investigational product for 6 months before this study

Sponsors & Collaborators

• Toscana Life Sciences Sviluppo s.r.l.: lead
• Cross Research S.A.: collaborator

Study Sites (2)

Inmi 'L.Spallanzani' - Irccs

Rome, Lazio, 00149, Italy

Location

Crc - Verona

Verona, Veneto, 37134, Italy

Location

Related Publications (2)

• Lanini S, Milleri S, Andreano E, Nosari S, Paciello I, Piccini G, Gentili A, Phogat A, Hyseni I, Leonardi M, Torelli A, Montomoli E, Paolini A, Frosini A, Antinori A, Nicastri E, Girardi E, Plazzi MM, Ippolito G, Vaia F, Della Cioppa G, Rappuoli R. Safety and serum distribution of anti-SARS-CoV-2 monoclonal antibody MAD0004J08 after intramuscular injection. Nat Commun. 2022 Apr 27;13(1):2263. doi: 10.1038/s41467-022-29909-x.

  PMID: 35477725 DERIVED

• 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

• Andrea Paolini

  Toscana Life Sciences Sviluppo s.r.l.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Identical kits for active and placebo will be provided.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 15, 2021
• First Posted: June 21, 2021
• Study Start: March 1, 2021
• Primary Completion: October 20, 2021
• Study Completion: October 20, 2021
• Last Updated: April 27, 2022

Record last verified: 2022-04

Locations

IT (2)