Ignite Creation Date:
2024-05-06 @ 4:17 PM
Last Modification Date:
2024-10-26 @ 2:07 PM
Study NCT ID:
NCT04932850
Status:
COMPLETED
Last Update Posted:
2022-04-27
First Post:
2021-06-15
Brief Title:
Study to Evaluate the Safety and Concentrations of Monoclonal Antibody Against Virus That Causes COVID-19 Disease
Sponsor:
Toscana Life Sciences Sviluppo srl
Organization:
Toscana Life Sciences Sviluppo srl
Study Overview
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
Status:
COMPLETED
Status Verified Date:
2022-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
MAD0004J08
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 InclusionExclusion 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
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 InclusionExclusion 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 subjectscohort 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
GoNo-go decision on escalation from Cohort 1 to Cohort 2 and from Cohort 2 to Cohort 3 will be taken after evaluation of Cohort 1Cohort 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
Previousconcomitant 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
Inclusionexclusion 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
Inclusionexclusion 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
Inclusionexclusion 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 152
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 222
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 303
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 604
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 1204 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 1807 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 SA 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 93 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 63 or higher Pharsight Corporation and SAS version 93 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
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 subjectscohort 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
GoNo-go decision on escalation from Cohort 1 to Cohort 2 and from Cohort 2 to Cohort 3 will be taken after evaluation of Cohort 1Cohort 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
Previousconcomitant 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
Inclusionexclusion 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
Inclusionexclusion 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
Inclusionexclusion 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 152
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 222
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 303
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 604
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 1204 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 1807 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 SA 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 93 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 63 or higher Pharsight Corporation and SAS version 93 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 2020-005469-15 | EUDRACT_NUMBER | None | None |