Phase 1 Safety and Pharmacokinetics Studies of BRII-196 and BRII-198, SARS-CoV-2 Spike-Targeting Monoclonal Antibodies
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Abstract
Background
BRII-196 and BRII-198 are two anti-SARS-CoV-2 monoclonal neutralizing antibodies with modified Fc region that extends half-life and are being developed as cocktail therapy for the treatment of COVID-19. Safety, tolerability, pharmacokinetics, and immunogenicity of BRII-196 and BRII-198 were investigated in healthy adults.
Methods
Single ascending doses of BRII-196 and BRII-198 were evaluated in parallel in the first-in-human, placebo-controlled phase 1 studies. A total of 32 healthy adults were randomized and received a single intravenous infusion of 750, 1500, and 3000 mg of BRII-196 (n=12), BRII-198 (n=12), or placebo (n=8) and were followed for 180 days.
Results
All infusions were well tolerated at infusion rates between 0.5 mL/min to 4 mL/min with no dose-limiting adverse events, deaths, serious adverse events, or any systemic or local infusion reactions. Most treatment-emergent adverse events were isolated asymptomatic laboratory abnormalities of Grade 1-2 in severity. Each mAb displayed pharmacokinetics expected of Fc-engineered human IgG1 with mean terminal half-lives of approximately 46 days and 76 days, respectively, with no evidence of significant anti-drug antibody development.
Conclusions
BRII-196 and BRII-198 were well-tolerated. Clinical results support further development as therapeutic or prophylactic options for SARS-CoV-2 infection.
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SciScore for 10.1101/2021.07.21.21260964: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Field Sample Permit: These studies were conducted at a single phase 1 unit in China from July 2020 to February 2021 (registered at ClinicalTrials.gov under registration number NCT04479631 and NCT04479644).
IACUC: The study protocol, amendments, and informed-consent forms were reviewed and approved by Ethical Review Committee at the site.
Consent: Participants provided written informed consent before any study-related procedures were performed.Sex as a biological variable Eligible participants were healthy male or female adults aged 18 to 49 years, had a body weight ≤100 kg and a body mass index of 18-24 kg/m2, and were in good health determined by no clinically significant findings from … SciScore for 10.1101/2021.07.21.21260964: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Field Sample Permit: These studies were conducted at a single phase 1 unit in China from July 2020 to February 2021 (registered at ClinicalTrials.gov under registration number NCT04479631 and NCT04479644).
IACUC: The study protocol, amendments, and informed-consent forms were reviewed and approved by Ethical Review Committee at the site.
Consent: Participants provided written informed consent before any study-related procedures were performed.Sex as a biological variable Eligible participants were healthy male or female adults aged 18 to 49 years, had a body weight ≤100 kg and a body mass index of 18-24 kg/m2, and were in good health determined by no clinically significant findings from medical history, physical examination including vital signs, electrocardiogram (ECG), and clinical laboratory assessments. Randomization Study design and participants: BRII-196-001 and BRII-198-001 are two first-in-human phase 1, randomized, single-blind, placebo-controlled, single ascending dose escalation studies in which BRII-196 and BRII-198 were evaluated respectively among healthy adults. Blinding not detected. Power Analysis not detected. Cell Line Authentication Authentication: BRII-196 or BRII-198 serum concentrations were measured using validated enzyme linked immunosorbent assays (ELISA) with the lower limit of quantitation (LLOQ) at 150 ng/mL. Table 2: Resources
Antibodies Sentences Resources Serum samples for anti-drug antibody (ADA) assays were collected at the following time points: pre-dose on day 1 and at days 15, 31, and 181. anti-drugsuggested: NoneSoftware and Algorithms Sentences Resources The PK parameters were estimated by non-compartmental analyses using WinNonlin module in the Phoenix Platform (version 8.3.1.5014, Certara Inc., Princeton, NJ 08540). Phoenix Platformsuggested: NoneResults from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT04479631 Completed Safety, Tolerability, and Pharmacokinetics Study of Human Mo… NCT04479644 Completed Safety, Tolerability, and Pharmacokinetics Study of Human Mo… Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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