Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Study to Evaluate the Safety and Concentrations of Monoclonal Antibody Against Virus That Causes COVID-19 Disease. (MAD0004J08)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04932850
Recruitment Status : Active, not recruiting
First Posted : June 21, 2021
Last Update Posted : June 21, 2021
Sponsor:
Collaborator:
Cross Research S.A.
Information provided by (Responsible Party):
Toscana Life Sciences Sviluppo s.r.l.

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) .


Condition or disease Intervention/treatment Phase
COVID-19 Virus Disease Biological: MAD0004J08 Other: Placebo Phase 1

Show Show detailed description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Identical kits for active and placebo will be provided.
Primary Purpose: Treatment
Official Title: COVID-19: A Phase I Dose-escalation Study to Evaluate the Safety and Pharmacokinetics of Anti-SARS-CoV-2 Monoclonal Antibody MAD0004J08 in Healthy Adults.
Actual Study Start Date : March 1, 2021
Estimated Primary Completion Date : October 2021
Estimated Study Completion Date : October 2021

Arm Intervention/treatment
Experimental: Active

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
Human mAb 100 mg / 2.5 mL solution for injection

Placebo Comparator: Placebo
Placebo will be administered to 2 subjects for each cohort.
Other: Placebo
Placebo matching to MAD0004J08 2.5 mL solution for injection




Primary Outcome Measures :
  1. Severe/serious treatment-emergent adverse events [ Time Frame: From Day 1 to Day 8 ]
    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.


Secondary Outcome Measures :
  1. Unsolicited and solicited TEAE [ Time Frame: From Day 1 to Day 180 ]
    Proportion of subjects with any unsolicited and solicited TEAE (including clinically relevant laboratory abnormalities, vital signs, and adverse reactions at the injection site) up to each assessment time and throughout the study

  2. Peak Plasma Concentration (Cmax) [ Time Frame: At each visit from Day 1 to Day 180 ]
    Evaluation of MAD0004J08 serum concentrations and PK parameter Cmax after single dose of 48 mg, 100 mg and 400 mg.

  3. Area under the concentration-time curve from time zero to time t (AUC0-t) [ Time Frame: At each visit from Day 1 to Day 180 ]

    Evaluation of MAD0004J08 serum PK parameter (AUC0-t):

    - Area under the concentration-time curve from time zero to time t (AUC0-t) after single dose of 48 mg, 100 mg and 400 mg


  4. Area under the concentration vs. time curve up to infinity (AUC0-∞) [ Time Frame: At each visit from Day 1 to Day 180 ]

    Evaluation of MAD0004J08 serum PK parameter AUC0-∞:

    - Area under the concentration vs. time curve up to infinity (AUC0-∞) after single dose of 48 mg, 100 mg and 400 mg


  5. Time to achieve Cmax (tmax) [ Time Frame: At each visit from Day 1 to Day 180 ]
    Evaluation of MAD0004J08 serum concentrations and PK parameter tmax after single dose of 48 mg, 100 mg and 400 mg.

  6. Half-life (t1/2) [ Time Frame: At each visit from Day 1 to Day 180 ]
    Evaluation of MAD0004J08 serum concentrations and PK parameter t1/2 after single dose of 48 mg, 100 mg and 400 mg.

  7. Distribution volume (Vz/F) [ Time Frame: At each visit from Day 1 to Day 180 ]
    Evaluation of MAD0004J08 serum concentrations and PK parameter Vz/F after single dose of 48 mg, 100 mg and 400 mg.

  8. Total body clearance CLt/F [ Time Frame: At each visit from Day 1 to Day 180 ]
    Evaluation of MAD0004J08 serum concentrations and PK parameter CLt/F after single dose of 48 mg, 100 mg and 400 mg.

  9. Number ADA positive subjects [ Time Frame: At Day 1, Day 8, Week 2, Month 1, Month 4 and Month 6. ]
    Number and percentage of ADA positive subjects and mean maximum ADA concentration after single dose of 48 mg, 100 mg and 400 mg MAD0004J08

  10. Percentage of ADA positive subjects [ Time Frame: At Day 1, Day 8, Week 2, Month 1, Month 4 and Month 6. ]
    Number and percentage of ADA positive subjects and mean maximum ADA concentration after single dose of 48 mg, 100 mg and 400 mg MAD0004J08

  11. Neutralising power analysis [ Time Frame: At Day 1,Day 3, Day 8, Month 1, Month 4 and Month 6. ]
    Serum neutralising power at baseline, 48 h post-dose, on day 8, at 1 month (day 30±3), 4 months (day 120±4) and 6 months (180±7) after single dose of 48 mg, 100 mg and 400 mg MAD0004J08


Other Outcome Measures:
  1. ELISA DIESSE kit characterisation [ Time Frame: At Day 1,Day 3, Day 8, Month 1, Month 4 and Month 6. ]

    Characterisation of DIESSE ELISA kit on serum samples at baseline, 48 h post-dose, on day 8, at 1 month (day 30±3), 4 months (day 120±4) and 6 months (180±7). A blood sample will be used to evaluate if Diesse Kit, developped by Toscana Life Sciences, would be able to detect administered MAD0004J08.

    This kit is not used to monitor study paramethers.




Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Informed consent: Signed written informed consent before inclusion in the study
  2. 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
  3. Sex and age: Healthy men and women, 18 - 55 years old, inclusive
  4. Negative SARS-CoV-2 serology test at screening (negative anti-S and anti-N)
  5. Negative SARS-CoV-2 qRT-PCR in the 72 h before treatment (test on day -3 or -2 or -1 with result before treatment)
  6. Body Mass Index: 18.5-30 kg/m2, inclusive, at screening
  7. 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
  8. ECG: Electrocardiogram without clinically significant abnormalities at screening
  9. 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:

    1. Hormonal oral or implantable or transdermal, or injectable contraceptives for at least 2 months before the screening visit;
    2. 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
    3. A male sexual partner who agrees to use a male condom with spermicide
    4. A sterile sexual partner
    5. 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

Exclusion Criteria:

  1. Physical findings: Clinically significant abnormal physical findings which could interfere with the objectives of the study
  2. 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
  3. 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)
  4. Monoclonal Antibodies (mAb): Previous intake of a mAb within 6 months, or 5 antibody half-life, whichever is longer, before study start
  5. 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
  6. 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
  7. SARS CoV-2 or COVID-19:

    1. Participants with any confirmed current or previous COVID-19 infection at screening, or at day -1 or day 1
    2. 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
    3. 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
    4. Has been reported as a case (confirmed or probable) of COVID-19 from the regional health system
  8. 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.
  9. 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
  10. Laboratory analyses: Abnormal laboratory values that in the opinion of the Investigator are clinically significant
  11. Investigative drug studies: Participation in the evaluation of any investigational product for 6 months before this study
  12. Blood donation: blood donations for 3 months before the study, during the study and in the 3 months after the end of the study
  13. Drug test: positive drug test at screening or day -1
  14. Drug, alcohol: history of drug or alcohol abuse within 6 months before screening
  15. Pregnancy (women only): positive or missing pregnancy test at screening or day 1; pregnant or lactating women
  16. Other: Any condition that might compromise study subject's safety or interfere with the study evaluations or interpretation of subject's safety or study results

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04932850


Locations
Layout table for location information
Italy
Inmi 'L.Spallanzani' - Irccs
Roma, Lazio, Italy, 00149
Crc - Verona
Verona, Veneto, Italy, 37134
Sponsors and Collaborators
Toscana Life Sciences Sviluppo s.r.l.
Cross Research S.A.
Investigators
Layout table for investigator information
Study Director: Andrea Paolini Toscana Life Sciences Sviluppo s.r.l.
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Toscana Life Sciences Sviluppo s.r.l.
ClinicalTrials.gov Identifier: NCT04932850    
Other Study ID Numbers: A0001A
2020-005469-15 ( EudraCT Number )
First Posted: June 21, 2021    Key Record Dates
Last Update Posted: June 21, 2021
Last Verified: June 2021

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Toscana Life Sciences Sviluppo s.r.l.:
COVID-19 Pandemic
SARS-CoV-2 Infection
SARS-CoV-2 Monoclonal Antibody
Additional relevant MeSH terms:
Layout table for MeSH terms
COVID-19
Virus Diseases
Respiratory Tract Infections
Infections
Pneumonia, Viral
Pneumonia
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases