COVID-19 Virus DiseasePhase 1MAD0004J08NCT04932850
Study to Evaluate the Safety and Concentrations of Monoclonal Antibody Against Virus That Causes COVID-19 Disease.
A Phase 1 study testing MAD0004J08 in people with COVID-19 Virus Disease, run by Toscana Life Sciences Sviluppo s.r.l. at 2 sites in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- COVID-19 Virus Disease
- What is being tested?
- MAD0004J08
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 2 sitesItaly
- Study dates
- 1 Mar 2021to 20 Oct 2021
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Informed consent: Signed written informed consent before inclusion in the study
- 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
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- 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
Who cannot join
- 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
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- 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
- Blood donation: blood donations for 3 months before the study, during the study and in the 3 months after the end of the study
- Drug test: positive drug test at screening or day -1
- Drug, alcohol: history of drug or alcohol abuse within 6 months before screening
- Pregnancy (women only): positive or missing pregnancy test at screening or day 1; pregnant or lactating women
- 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
Trial locations and contacts
2 sites in 1 country.
Italy2 sites
Inmi 'L.Spallanzani' - Irccs
Rome, Lazio, 00149
Crc - Verona
Verona, Veneto, 37134
About this study
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.
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.
Read more
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) .
Read the detailed description
A Phase I dose-escalation study to evaluate the safety and pharmacokinetics of anti-SARSCoV- 2 monoclonal antibody MAD0004J08 in healthy adults.
Two Italian clinical sites are involved in the study. It is a first-in-human, single-dose, dose-escalation, double-blind, placebo-controlled, randomised, safety and pharmacokinetics study.
Three single ascending doses (48 mg, 100 mg and 400 mg) and placebo will be administered by intramuscular injection to three study cohorts (10 subjects/cohort) as single doses, in the morning of day 1.
There are 5 sentinel subjects for each Cohort, they will be treated one at the time at 48 h distance (after evaluation of any possible treatment related adverse event).
Active treatment and placebo will be assigned within each cohort and group according to the study randomisation list.
Go/No-go decision on escalation from Cohort 1 to Cohort 2 and from Cohort 2 to Cohort 3 will be taken after evaluation of Cohort 1/Cohort 2 safety data up to 48 h post-dose by an independent Data Safety Monitoring Board.
The primary objective of the study is to evaluate the safety of three single dose levels of MAD0004J08 in healthy subjects.
Secondary objectives are to evaluate the pharmacokinetics of MAD0004J08, potency in terms of serum neutralisation power and immunogenicity in terms of generation of anti-drug antibodies (ADAs) after single dose of 48 mg, 100 mg and 400 mg.
The following procedures will be performed:
Visit 1 - Screening Day -21 / Day -2
- Explanation to the subject of study aims, procedures and possible risks
- Informed consent signature
- Screening number assignment (as S001, S002, etc.)
- Demographic data and life style recording
- Medical history
- Previous/concomitant medications
- Physical examination (including body weight, height)
- Vital signs (blood pressure, heart rate, body temperature)
- 12-lead Electrocardiogram (ECG)
- SARS-CoV-2 serology test
- Laboratory analyses: haematology, blood chemistry, urinalysis, serum virology, coagulation, ferritin
- Drug of abuse test
- Urinary pregnancy test (women)
- SARS-CoV-2 Real-Time Quantitative Reverse Transcription PCR (qRT-PCR) in the 72 h before day 1 (could be performed on day -3 or day-2 or day -1)
- Adverse event monitoring
- Inclusion/exclusion criteria evaluation
- Eligibility evaluation Visit 2 - Day -1
- SARS-CoV-2 qRT-PCR in the 72 h before treatment. On day -1 either test performance, or result check if already performed on day -3 or day -2
- Drug of abuse test
- Inclusion/exclusion criteria evaluation
- Check of AEs and concomitant medications
- Vital signs (blood pressure, heart rate, body temperature)
- Physical examination
- Eligibility evaluation Visit 3 - Day 1
- Urine pregnancy test (women)
- Inclusion/exclusion criteria evaluation, eligibility evaluation, and randomisation
- 12-lead ECG
- Dispensation of 2 diaries to the subject (diary 1 to report solicited adverse events from day 1 to day 8, diary 2 to report all unsolicited adverse events and concomitant medication from day 1 to month 1)
- Laboratory analyses: haematology, coagulation, blood chemistry, urinalysis, SARS-CoV-2 serology test - baseline
- Blood sample collection for pharmacokinetic analysis at predose (0) and 1h, 2h, 3h, 4h, 6h, 8h, 12h post-dose
- Blood sample collection for ADA analysis at pre-dose (0)
- Blood sample collection for serum neutralising power test at pre-dose (0)
- Blood sample collection for DIESSE Elisa kit characterisation at pre-dose (0)
- Vital signs (blood pressure, heart rate, body temperature) measurement at pre-dose (0), 2h post-dose and 12 h post-dose
- Investigational product administration (active or placebo according to study Cohort, Group and randomisation)
- Adverse events monitoring
- Injection site reactions check
- Concomitant medications check Visit 4 - Day 2
- Physical examination
- Vital signs (blood pressure, heart rate, body temperature) measurement at 24 h post-dose
- Blood sample collection for pharmacokinetic analysis at 24h post-dose
- Adverse events monitoring
- Injection site reactions check
- Diary 1 and diary 2 check
- Concomitant medications check
- Laboratory analyses: haematology, blood chemistry, coagulation, urinalysis, SARS-CoV-2 serology test at 24 h post-dose
- 12-lead ECG at 24 h post-dose Visit 5 - Day 3
- Vital signs (blood pressure, heart rate, body temperature) measurement at 48 h post-dose
- Blood sample collection for pharmacokinetic analysis at 48h post-dose
- Blood sample collection for serum neutralising power test at 48h post-dose
- Blood sample collection for DIESSE Elisa kit characterisation at 48 h post-dose
- Adverse events monitoring
- Injection site reactions check
- Diary 1 and diary 2 check
- Concomitant medications check
- Laboratory analyses: haematology, blood chemistry, coagulation, urinalysis, SARS-CoV-2 serology test - at 48 h post-dose
- Physical examination Visits 6 / Week 1 / Day 8 and Visit 7 / Week 2 / Day 15±2
- Physical examination
- Vital signs (blood pressure, heart rate, body temperature) measurement
- Blood sample collection for pharmacokinetic analysis
- Blood sample collection for ADA analysis
- Blood sample collection for serum neutralising power test on day 8 only
- Blood sample collection for DIESSE Elisa kit characterisation on day 8 only
- Adverse events monitoring
- Concomitant medications check
- Laboratory analyses: haematology, blood chemistry, coagulation, urinalysis, SARS-CoV-2 serology test
- Diary 1 check - day 8 only
- Diary 2 check - day 8 and day 15
- Subjects' diary 1 return - day 8 only Visit 8 Week 3 Day 22±2
- Physical examination
- Vital signs (blood pressure, heart rate, body temperature)
- Blood sample collection for pharmacokinetic analysis
- Adverse events monitoring
- Diary 2 check
- Concomitant medications check
- Laboratory analyses: haematology, blood chemistry, coagulation, urinalysis, SARS-CoV-2 serology test Visit 9 - 1 month Day 30±3
- Physical examination
- Vital signs (blood pressure, heart rate, body temperature) measurement
- Blood sample collection for pharmacokinetic analysis
- Blood sample collection for ADA analysis
- Blood sample collection for serum neutralising power test
- Blood sample collection for DIESSE Elisa kit characterisation
- Adverse events monitoring
- Diary 2 check
- Concomitant medications check
- Laboratory analyses: haematology, blood chemistry, coagulation, urinalysis, SARS-CoV-2 serology test
- Urine pregnancy test (women)
- Subjects' diary 2 return Visit 10 - 2 months Day 60±4
- Physical examination
- Vital signs (blood pressure, heart rate, body temperature) measurement
- Blood sample collection for pharmacokinetic analysis
- Adverse events monitoring
- Concomitant medications check
- Laboratory analyses: haematology, blood chemistry, coagulation, urinalysis, SARS-CoV-2 serology test
- Urine pregnancy test (women) Visit 11 - 4 months Day 120±4 days
- Physical examination
- Vital signs (blood pressure, heart rate, body temperature) measurement
- Blood sample collection for pharmacokinetic analysis
- Blood sample collection for ADA
- Blood sample collection for serum neutralising power test
- Blood sample collection for DIESSE Elisa kit characterisation
- Adverse events monitoring
- Concomitant medications check
- Laboratory analyses: haematology, blood chemistry, coagulation, urinalysis, SARS-CoV-2 serology test
- Urine pregnancy test (women) Visit 12 - 6 months Final visit Day 180±7 days
- Physical examination (including body weight)
- Vital signs (blood pressure, heart rate, body temperature) measurement
- Blood sample collection for pharmacokinetic analysis
- Blood sample collection for ADA
- Blood sample collection for serum neutralising power test
- Blood sample collection for DIESSE Elisa kit characterisation
- Adverse events monitoring
- Concomitant medications check
- Laboratory analyses: haematology, blood chemistry, urinalysis, coagulation, SARS-CoV-2 serology test
- 12-lead ECG The data documented in this trial and the measured clinical parameters will be presented using classic descriptive statistics for quantitative variables and frequencies for qualitative variables.
A Statistical Analysis Plan will be prepared by CROSS Research S.A. Biometry Unit, approved by the Sponsor and finalised before database lock.
Safety, serum neutralising power, immunogenicity and demography data will be analysed by CROSS Research Biometry Unit using SAS® version 9.3 (TS1M1) or higher (the actual version will be stated in the final report).
Adverse events and serious adverse events (including clinically significant laboratory parameters, vital signs, ECG results and adverse reactions at the injection sites) will be listed by treatment. Number and percentage of subjects with adverse events and serious adverse events will be summarised.
Serum MAD0004J08 concentrations and pharmacokinetic parameters will be analysed using Phoenix WinNonlin® validated version 6.3 or higher (Pharsight Corporation) and SAS® version 9.3 for Windows® or higher. Pharmacokinetics data will be listed and summarised by descriptive statistics. Individual and mean concentration curves will also be generated. ADA concentrations will be summarised by descriptive statistics. Number and percentage of ADA-positive subjects will be listed and summarised by assessment time and overall. Serum neutralising power results will be listed by subject and assessment time-point and summarised by descriptive statistics.
- Conditions
- COVID-19 Virus Disease
- Being tested
- MAD0004J08, Placebo
- Keywords
- COVID-19 Pandemic, SARS-CoV-2 Infection, SARS-CoV-2 Monoclonal Antibody
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MAD0004J08Biological
Human mAb 100 mg / 2.5 mL solution for injection
PlaceboOther
Placebo matching to MAD0004J08 2.5 mL solution for injection
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Biological: MAD0004J08 |
| Placebo | Placebo comparator | Placebo will be administered to 2 subjects for each cohort. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From Day 1 to Day 8
Secondary outcomes (11)
Unsolicited and solicited TEAE
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
Measured: From Day 1 to Day 180
Peak Plasma Concentration (Cmax)
Evaluation of MAD0004J08 serum concentrations and PK parameter Cmax after single dose of 48 mg, 100 mg and 400 mg.
Measured: At each visit from Day 1 to Day 180
Area under the concentration-time curve from time zero to time t (AUC0-t)
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
Measured: At each visit from Day 1 to Day 180
Area under the concentration vs. time curve up to infinity (AUC0-∞)
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
Measured: At each visit from Day 1 to Day 180
Time to achieve Cmax (tmax)
Evaluation of MAD0004J08 serum concentrations and PK parameter tmax after single dose of 48 mg, 100 mg and 400 mg.
Measured: At each visit from Day 1 to Day 180
Half-life (t1/2)
Evaluation of MAD0004J08 serum concentrations and PK parameter t1/2 after single dose of 48 mg, 100 mg and 400 mg.
Measured: At each visit from Day 1 to Day 180
Distribution volume (Vz/F)
Evaluation of MAD0004J08 serum concentrations and PK parameter Vz/F after single dose of 48 mg, 100 mg and 400 mg.
Measured: At each visit from Day 1 to Day 180
Total body clearance CLt/F
Evaluation of MAD0004J08 serum concentrations and PK parameter CLt/F after single dose of 48 mg, 100 mg and 400 mg.
Measured: At each visit from Day 1 to Day 180
Number ADA positive subjects
Number and percentage of ADA positive subjects and mean maximum ADA concentration after single dose of 48 mg, 100 mg and 400 mg MAD0004J08
Measured: At Day 1, Day 8, Week 2, Month 1, Month 4 and Month 6.
Percentage of ADA positive subjects
Number and percentage of ADA positive subjects and mean maximum ADA concentration after single dose of 48 mg, 100 mg and 400 mg MAD0004J08
Measured: At Day 1, Day 8, Week 2, Month 1, Month 4 and Month 6.
Neutralising power analysis
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
Measured: At Day 1,Day 3, Day 8, Month 1, Month 4 and Month 6.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jun 2021
- Study start1 Mar 2021
- Primary completion20 Oct 2021
- Study completion20 Oct 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for COVID-19 Virus DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Toscana Life Sciences Sviluppo s.r.l.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Cross Research S.A.
- Responsible party
- Sponsor
- Investigators
- Andrea Paolini, Study director, Toscana Life Sciences Sviluppo s.r.l.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04932850
- Sponsor's protocol ID
- A0001A
- Other IDs
- 2020-005469-15
- Acronym
- MAD0004J08
- Status last verified
- Apr 2022
- First submitted
- 15 Jun 2021
- Last updated
- 27 Apr 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 35477725Kreuzberger 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.
PubMed 34473343
Study at a glance
From the registry record, last updated by the sponsor on 27 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT04932850
- Acronym / sponsor ID
- MAD0004J08 / A0001A
- Conditions
- COVID-19 Virus Disease
- Keywords
- COVID-19 Pandemic, SARS-CoV-2 Infection, SARS-CoV-2 Monoclonal Antibody
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Toscana Life Sciences Sviluppo s.r.l.Industry (pharma, biotech, devices)
- Collaborators
- Cross Research S.A.
- Study start
- 1 Mar 2021 (actual)
- Primary completion
- 20 Oct 2021 (actual)
- Study completion
- 20 Oct 2021 (actual)
- First posted
- 21 Jun 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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) .
Detailed description
A Phase I dose-escalation study to evaluate the safety and pharmacokinetics of anti-SARSCoV- 2 monoclonal antibody MAD0004J08 in healthy adults.
Two Italian clinical sites are involved in the study. It is a first-in-human, single-dose, dose-escalation, double-blind, placebo-controlled, randomised, safety and pharmacokinetics study.
Three single ascending doses (48 mg, 100 mg and 400 mg) and placebo will be administered by intramuscular injection to three study cohorts (10 subjects/cohort) as single doses, in the morning of day 1.
There are 5 sentinel subjects for each Cohort, they will be treated one at the time at 48 h distance (after evaluation of any possible treatment related adverse event).
Active treatment and placebo will be assigned within each cohort and group according to the study randomisation list.
Go/No-go decision on escalation from Cohort 1 to Cohort 2 and from Cohort 2 to Cohort 3 will be taken after evaluation of Cohort 1/Cohort 2 safety data up to 48 h post-dose by an independent Data Safety Monitoring Board.
The primary objective of the study is to evaluate the safety of three single dose levels of MAD0004J08 in healthy subjects.
Secondary objectives are to evaluate the pharmacokinetics of MAD0004J08, potency in terms of serum neutralisation power and immunogenicity in terms of generation of anti-drug antibodies (ADAs) after single dose of 48 mg, 100 mg and 400 mg.
The following procedures will be performed:
Visit 1 - Screening Day -21 / Day -2
- Explanation to the subject of study aims, procedures and possible risks
- Informed consent signature
- Screening number assignment (as S001, S002, etc.)
- Demographic data and life style recording
- Medical history
- Previous/concomitant medications
- Physical examination (including body weight, height)
- Vital signs (blood pressure, heart rate, body temperature)
- 12-lead Electrocardiogram (ECG)
- SARS-CoV-2 serology test
- Laboratory analyses: haematology, blood chemistry, urinalysis, serum virology, coagulation, ferritin
- Drug of abuse test
- Urinary pregnancy test (women)
- SARS-CoV-2 Real-Time Quantitative Reverse Transcription PCR (qRT-PCR) in the 72 h before day 1 (could be performed on day -3 or day-2 or day -1)
- Adverse event monitoring
- Inclusion/exclusion criteria evaluation
- Eligibility evaluation Visit 2 - Day -1
- SARS-CoV-2 qRT-PCR in the 72 h before treatment. On day -1 either test performance, or result check if already performed on day -3 or day -2
- Drug of abuse test
- Inclusion/exclusion criteria evaluation
- Check of AEs and concomitant medications
- Vital signs (blood pressure, heart rate, body temperature)
- Physical examination
- Eligibility evaluation Visit 3 - Day 1
- Urine pregnancy test (women)
- Inclusion/exclusion criteria evaluation, eligibility evaluation, and randomisation
- 12-lead ECG
- Dispensation of 2 diaries to the subject (diary 1 to report solicited adverse events from day 1 to day 8, diary 2 to report all unsolicited adverse events and concomitant medication from day 1 to month 1)
- Laboratory analyses: haematology, coagulation, blood chemistry, urinalysis, SARS-CoV-2 serology test - baseline
- Blood sample collection for pharmacokinetic analysis at predose (0) and 1h, 2h, 3h, 4h, 6h, 8h, 12h post-dose
- Blood sample collection for ADA analysis at pre-dose (0)
- Blood sample collection for serum neutralising power test at pre-dose (0)
- Blood sample collection for DIESSE Elisa kit characterisation at pre-dose (0)
- Vital signs (blood pressure, heart rate, body temperature) measurement at pre-dose (0), 2h post-dose and 12 h post-dose
- Investigational product administration (active or placebo according to study Cohort, Group and randomisation)
- Adverse events monitoring
- Injection site reactions check
- Concomitant medications check Visit 4 - Day 2
- Physical examination
- Vital signs (blood pressure, heart rate, body temperature) measurement at 24 h post-dose
- Blood sample collection for pharmacokinetic analysis at 24h post-dose
- Adverse events monitoring
- Injection site reactions check
- Diary 1 and diary 2 check
- Concomitant medications check
- Laboratory analyses: haematology, blood chemistry, coagulation, urinalysis, SARS-CoV-2 serology test at 24 h post-dose
- 12-lead ECG at 24 h post-dose Visit 5 - Day 3
- Vital signs (blood pressure, heart rate, body temperature) measurement at 48 h post-dose
- Blood sample collection for pharmacokinetic analysis at 48h post-dose
- Blood sample collection for serum neutralising power test at 48h post-dose
- Blood sample collection for DIESSE Elisa kit characterisation at 48 h post-dose
- Adverse events monitoring
- Injection site reactions check
- Diary 1 and diary 2 check
- Concomitant medications check
- Laboratory analyses: haematology, blood chemistry, coagulation, urinalysis, SARS-CoV-2 serology test - at 48 h post-dose
- Physical examination Visits 6 / Week 1 / Day 8 and Visit 7 / Week 2 / Day 15±2
- Physical examination
- Vital signs (blood pressure, heart rate, body temperature) measurement
- Blood sample collection for pharmacokinetic analysis
- Blood sample collection for ADA analysis
- Blood sample collection for serum neutralising power test on day 8 only
- Blood sample collection for DIESSE Elisa kit characterisation on day 8 only
- Adverse events monitoring
- Concomitant medications check
- Laboratory analyses: haematology, blood chemistry, coagulation, urinalysis, SARS-CoV-2 serology test
- Diary 1 check - day 8 only
- Diary 2 check - day 8 and day 15
- Subjects' diary 1 return - day 8 only Visit 8 Week 3 Day 22±2
- Physical examination
- Vital signs (blood pressure, heart rate, body temperature)
- Blood sample collection for pharmacokinetic analysis
- Adverse events monitoring
- Diary 2 check
- Concomitant medications check
- Laboratory analyses: haematology, blood chemistry, coagulation, urinalysis, SARS-CoV-2 serology test Visit 9 - 1 month Day 30±3
- Physical examination
- Vital signs (blood pressure, heart rate, body temperature) measurement
- Blood sample collection for pharmacokinetic analysis
- Blood sample collection for ADA analysis
- Blood sample collection for serum neutralising power test
- Blood sample collection for DIESSE Elisa kit characterisation
- Adverse events monitoring
- Diary 2 check
- Concomitant medications check
- Laboratory analyses: haematology, blood chemistry, coagulation, urinalysis, SARS-CoV-2 serology test
- Urine pregnancy test (women)
- Subjects' diary 2 return Visit 10 - 2 months Day 60±4
- Physical examination
- Vital signs (blood pressure, heart rate, body temperature) measurement
- Blood sample collection for pharmacokinetic analysis
- Adverse events monitoring
- Concomitant medications check
- Laboratory analyses: haematology, blood chemistry, coagulation, urinalysis, SARS-CoV-2 serology test
- Urine pregnancy test (women) Visit 11 - 4 months Day 120±4 days
- Physical examination
- Vital signs (blood pressure, heart rate, body temperature) measurement
- Blood sample collection for pharmacokinetic analysis
- Blood sample collection for ADA
- Blood sample collection for serum neutralising power test
- Blood sample collection for DIESSE Elisa kit characterisation
- Adverse events monitoring
- Concomitant medications check
- Laboratory analyses: haematology, blood chemistry, coagulation, urinalysis, SARS-CoV-2 serology test
- Urine pregnancy test (women) Visit 12 - 6 months Final visit Day 180±7 days
- Physical examination (including body weight)
- Vital signs (blood pressure, heart rate, body temperature) measurement
- Blood sample collection for pharmacokinetic analysis
- Blood sample collection for ADA
- Blood sample collection for serum neutralising power test
- Blood sample collection for DIESSE Elisa kit characterisation
- Adverse events monitoring
- Concomitant medications check
- Laboratory analyses: haematology, blood chemistry, urinalysis, coagulation, SARS-CoV-2 serology test
- 12-lead ECG The data documented in this trial and the measured clinical parameters will be presented using classic descriptive statistics for quantitative variables and frequencies for qualitative variables.
A Statistical Analysis Plan will be prepared by CROSS Research S.A. Biometry Unit, approved by the Sponsor and finalised before database lock.
Safety, serum neutralising power, immunogenicity and demography data will be analysed by CROSS Research Biometry Unit using SAS® version 9.3 (TS1M1) or higher (the actual version will be stated in the final report).
Adverse events and serious adverse events (including clinically significant laboratory parameters, vital signs, ECG results and adverse reactions at the injection sites) will be listed by treatment. Number and percentage of subjects with adverse events and serious adverse events will be summarised.
Serum MAD0004J08 concentrations and pharmacokinetic parameters will be analysed using Phoenix WinNonlin® validated version 6.3 or higher (Pharsight Corporation) and SAS® version 9.3 for Windows® or higher. Pharmacokinetics data will be listed and summarised by descriptive statistics. Individual and mean concentration curves will also be generated. ADA concentrations will be summarised by descriptive statistics. Number and percentage of ADA-positive subjects will be listed and summarised by assessment time and overall. Serum neutralising power results will be listed by subject and assessment time-point and summarised by descriptive statistics.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active | Experimental | Biological: MAD0004J083 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. |
| Placebo | Placebo comparator | Other: PlaceboPlacebo will be administered to 2 subjects for each cohort. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (14 listed)
- Informed consent: Signed written informed consent before inclusion in the study
- 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)
Key exclusion criteria (20 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MAD0004J08Human mAb 100 mg / 2.5 mL solution for injection | Biological | Active |
| PlaceboPlacebo matching to MAD0004J08 2.5 mL solution for injection | Other | Placebo |
Primary outcome
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.
11 secondary outcomes
Unsolicited and solicited TEAE
Time frame: From Day 1 to Day 180
Peak Plasma Concentration (Cmax)
Time frame: At each visit from Day 1 to Day 180
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
Area under the concentration vs. time curve up to infinity (AUC0-∞)
Time frame: At each visit from Day 1 to Day 180
Time to achieve Cmax (tmax)
Time frame: At each visit from Day 1 to Day 180
Half-life (t1/2)
Time frame: At each visit from Day 1 to Day 180
Distribution volume (Vz/F)
Time frame: At each visit from Day 1 to Day 180
Total body clearance CLt/F
Time frame: At each visit from Day 1 to Day 180
Number ADA positive subjects
Time frame: At Day 1, Day 8, Week 2, Month 1, Month 4 and Month 6.
Percentage of ADA positive subjects
Time frame: At Day 1, Day 8, Week 2, Month 1, Month 4 and Month 6.
Neutralising power analysis
Time frame: At Day 1,Day 3, Day 8, Month 1, Month 4 and Month 6.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Apr 2022.
- Derived from this study: PubMed 35477725Lanini 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.
- Derived from this study: PubMed 34473343Kreuzberger 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andrea Paolini study director
Toscana Life Sciences Sviluppo s.r.l.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing MAD0004J08 in people with COVID-19 Virus Disease, run by Toscana Life Sciences Sviluppo s.r.l. at 2 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Severe/serious treatment-emergent adverse events (time frame: From Day 1 to Day 8). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04932850, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Apr 2022.