Clinical Trial Results:
A Phase 2a, Open-Label Study Assessing the Pharmacokinetics, Safety, Tolerability, and Immunogenicity of a Single Dose of Subcutaneous Anti-Spike SARS-CoV-2 Monoclonal Antibodies Casirivimab and Imdevimab in High-Risk Pediatric Subjects Under 12 Years of Age
Summary
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EudraCT number |
2021-004590-30 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
01 Jun 2022
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Results information
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Results version number |
v1(current) |
This version publication date |
15 Dec 2022
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First version publication date |
15 Dec 2022
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
R10933-10987-COV-2121
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04992273 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Regeneron Pharmaceuticals, Inc.
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Sponsor organisation address |
777 Old Saw Mill River Road, Tarrytown, United States, NY
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Public contact |
Clinical Trials Administrator, Regeneron Pharmaceuticals, Inc., 001 8447346643, clinicaltrials@regeneron.com
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Scientific contact |
Clinical Trials Administrator, Regeneron Pharmaceuticals, Inc., 001 8447346643, clinicaltrials@regeneron.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
Yes
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EMA paediatric investigation plan number(s) |
EMEA-002964-PIP01-21 | ||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
01 Jun 2022
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
01 Jun 2022
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
This was an open-label, phase 2a study to assess the pharmacokinetics, safety, tolerability, and immunogenicity of casirivimab+imdevimab in participants <12 years old who were not infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) but are at high risk to develop severe coronavirus disease 2019 (COVID-19) if they became infected.
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Protection of trial subjects |
It is the responsibility of both the sponsor and the investigator(s) to ensure that this clinical study will be conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki, and that are consistent with the ICH guidelines for GCP and applicable regulatory requirements.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
13 Sep 2021
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United States: 7
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Worldwide total number of subjects |
7
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EEA total number of subjects |
0
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
1
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Children (2-11 years) |
6
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
- | |||||||||||||||
Pre-assignment
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Screening details |
A total of 7 participants were screened & enrolled into Group A (≥10 kg to <40 kg). One discontinued at week 9 (lost to follow-up). Participants were subsequently divided into 2 groups: 2 participants in Group A1 (≥20 kg to <40 kg) & 5 in Group A2 (≥10 kg to <20 kg) & received different doses. All participants were enrolled & treated. | |||||||||||||||
Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | |||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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≥20 kg to <40 kg | |||||||||||||||
Arm description |
Single dose of casirivimab+imdevimab, that was the body weight dose equivalent to the 1200 mg adult dose (600 mg of casirivimab and 600 mg of imdevimab) administered as 1 to 4 subcutaneous (SC) injections based on body weight. | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
casirivimab
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
600 milligram (mg) administered as 1 to 4 subcutaneous (SC) injections based on body weight
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Investigational medicinal product name |
imdevimab
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
600 milligram (mg) administered as 1 to 4 subcutaneous (SC) injections based on body weight
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Arm title
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≥10 kg to <20 kg | |||||||||||||||
Arm description |
Single dose of casirivimab+imdevimab, that was the body weight dose equivalent to the 1200 mg adult dose (600 mg of casirivimab and 600 mg of imdevimab) administered as 1 to 4 subcutaneous (SC) injections based on body weight. | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
casirivimab
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
600 milligram (mg) administered as 1 to 4 subcutaneous (SC) injections based on body weight
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Investigational medicinal product name |
imdevimab
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
600 milligram (mg) administered as 1 to 4 subcutaneous (SC) injections based on body weight
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Baseline characteristics reporting groups
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Reporting group title |
≥20 kg to <40 kg
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Reporting group description |
Single dose of casirivimab+imdevimab, that was the body weight dose equivalent to the 1200 mg adult dose (600 mg of casirivimab and 600 mg of imdevimab) administered as 1 to 4 subcutaneous (SC) injections based on body weight. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
≥10 kg to <20 kg
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Reporting group description |
Single dose of casirivimab+imdevimab, that was the body weight dose equivalent to the 1200 mg adult dose (600 mg of casirivimab and 600 mg of imdevimab) administered as 1 to 4 subcutaneous (SC) injections based on body weight. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
≥10 kg to <40 kg
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Subject analysis set type |
Full analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Single dose of casirivimab+imdevimab, that was the body weight dose equivalent to the 1200 mg adult dose administered as 1 to 4 subcutaneous (SC) injections based on body weight.
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End points reporting groups
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Reporting group title |
≥20 kg to <40 kg
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Reporting group description |
Single dose of casirivimab+imdevimab, that was the body weight dose equivalent to the 1200 mg adult dose (600 mg of casirivimab and 600 mg of imdevimab) administered as 1 to 4 subcutaneous (SC) injections based on body weight. | ||
Reporting group title |
≥10 kg to <20 kg
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Reporting group description |
Single dose of casirivimab+imdevimab, that was the body weight dose equivalent to the 1200 mg adult dose (600 mg of casirivimab and 600 mg of imdevimab) administered as 1 to 4 subcutaneous (SC) injections based on body weight. | ||
Subject analysis set title |
≥10 kg to <40 kg
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Single dose of casirivimab+imdevimab, that was the body weight dose equivalent to the 1200 mg adult dose administered as 1 to 4 subcutaneous (SC) injections based on body weight.
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End point title |
Concentrations of casirivimab+imdevimab in serum over time [1] | ||||||||||||
End point description |
Concentrations reported in milligrams per Liter (mg/L)
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End point type |
Primary
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End point timeframe |
Up to 24 weeks
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive statistics were performed on this outcome measure. |
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No statistical analyses for this end point |
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End point title |
Number of Participants with Treatment-Emergent Adverse Events (TEAEs) | |||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Through end of study, approximately 24 weeks
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No statistical analyses for this end point |
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End point title |
Severity of TEAEs | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Through end of study, approximately 24 weeks
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No statistical analyses for this end point |
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End point title |
Number of Participants with Grade ≥3 Injection Site Reactions | |||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Through Day 4
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No statistical analyses for this end point |
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End point title |
Number of participants with grade ≥3 hypersensitivity reactions | |||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Through Day 4
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No statistical analyses for this end point |
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End point title |
Immunogenicity as measured by anti-drug antibodies (ADA) to casirivimab over time | |||||||||
End point description |
Negative response
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End point type |
Secondary
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End point timeframe |
Up to 24 weeks
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No statistical analyses for this end point |
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End point title |
Immunogenicity as measured by ADA to imdevimab over time | |||||||||
End point description |
Negative response
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End point type |
Secondary
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End point timeframe |
Up to 24 weeks
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No statistical analyses for this end point |
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End point title |
Immunogenicity as measured by neutralizing antibodies (NAb) to casirivimab over time | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Up to 24 weeks
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Notes [2] - Neutralizing antibody (NAb) analysis data was not collected. [3] - Neutralizing antibody (NAb) analysis data was not collected. |
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No statistical analyses for this end point |
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End point title |
Immunogenicity as measured by NAb to imdevimab over time | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Up to 24 weeks
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Notes [4] - Neutralizing antibody (NAb) analysis data was not collected. [5] - Neutralizing antibody (NAb) analysis data was not collected. |
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
From first dose to week 24
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
25.0
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Reporting groups
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Reporting group title |
Group A2 ≥10 kg to <20 kg
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Reporting group description |
Single dose of casirivimab+imdevimab, that was the body weight dose equivalent to the 1200 mg adult dose administered as 1 to 4 subcutaneous (SC) injections based on body weight. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Group A1 ≥20 kg to <40 kg
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Reporting group description |
Single dose of casirivimab+imdevimab, that was the body weight dose equivalent to the 1200 mg adult dose administered as 1 to 4 subcutaneous (SC) injections based on body weight. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||||||
Date |
Amendment |
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16 Sep 2021 |
Updated route of administration in participants with lower body weight (subcutaneous rather than
intramuscular), included additional sample collections for drug concentration assessment at later time points, and addition of an adverse event of special interest (AESI). |
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08 Mar 2022 |
Updates included shortening length of gollow-up period from 225 days to 169 days (32 weeks to 24 weeks), and to add that the end of study visit (EOS) visit is required to be performed in person. |
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Interruptions (globally) |
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Were there any global interruptions to the trial? Yes | |||||||
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Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||||||
None reported |