Randomized, placebo-controlled, single-blind phase 1 studies of the safety, tolerability, and pharmacokinetics of BRII-196 and BRII-198, SARS-CoV-2 spike-targeting monoclonal antibodies with an extended half-life in healthy adults

Hao, Xiaohua; Zhang, Zheng; Ma, Ji; Cheng, Lin; Ji, Yun; Liu, Yang; Zhao, Dong; Zhang, Wen; Li, Chunming; Li, Yan; Margolis, David; Zhu, Qing; Zhang, Yao; Zhang, Fujie

doi:10.3389/fphar.2022.983505

Cited by 10 publications

(4 citation statements)

References 14 publications

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“…[18,70,92,[102][103][104]. This treatment demonstrated a statistically significant reduction (by 78%) of relative risk (p = 0.00001) of hospitalization and death, compared with placebo, in 837 non-hospitalized COVID-19 patients at high risk of clinical progression [18,105,106].…”

Section: Xav-19mentioning

confidence: 89%

Severe COVID-19: Drugs and Clinical Trials

Ceja-Gálvez

Renteria-Flores

Nicoletti

et al. 2023

JCM

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By January of 2023, the COVID-19 pandemic had led to a reported total of 6,700,883 deaths and 662,631,114 cases worldwide. To date, there have been no effective therapies or standardized treatment schemes for this disease; therefore, the search for effective prophylactic and therapeutic strategies is a primary goal that must be addressed. This review aims to provide an analysis of the most efficient and promising therapies and drugs for the prevention and treatment of severe COVID-19, comparing their degree of success, scope, and limitations, with the aim of providing support to health professionals in choosing the best pharmacological approach. An investigation of the most promising and effective treatments against COVID-19 that are currently available was carried out by employing search terms including “Convalescent plasma therapy in COVID-19” or “Viral polymerase inhibitors” and “COVID-19” in the Clinicaltrials.gov and PubMed databases. From the current perspective and with the information available from the various clinical trials assessing the efficacy of different therapeutic options, we conclude that it is necessary to standardize certain variables—such as the viral clearance time, biomarkers associated with severity, hospital stay, requirement of invasive mechanical ventilation, and mortality rate—in order to facilitate verification of the efficacy of such treatments and to better assess the repeatability of the most effective and promising results.

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Section: Xav-19mentioning

confidence: 89%

Severe COVID-19: Drugs and Clinical Trials

Ceja-Gálvez

Renteria-Flores

Nicoletti

et al. 2023

JCM

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“…NAbs can rapidly reduce the viral load in COVID-19 patients, particularly in those with an uninitiated immune response or high baseline viral load, with the most substantial benefit observed in patients receiving exogenously supplied NAbs prior to initiating an immune response [4]. The extended half-life of BRII-196 and BRII-198 translates into stable drug concentrations during the therapeutic window and supports their use as an alternative for pre-exposure prophylaxis, addressing a significant global unmet need [16]. For example, it is estimated that 2.7% of the population is immunocompromised and not adequately protected by the COVID-19 vaccine [17].…”

Section: Effect Of Brii-196/brii-198 On Lymphocyte Count Recovery Tim...mentioning

confidence: 95%

“…Clinical trials have demonstrated therapeutic and prophylactic benefits of monoclonal antibodies [3,4]. Antibody drugs with high efficacy are crucial for short-term prevention of SARS-CoV-2 infection and treatment of COVID-19, playing a piv-Am J Transl Res 2024; 16(3):916-924 otal role in epidemic management and control. To address the continuous mutation of SARS-CoV-2 and the widespread emergence of variants, cocktail therapies combining multiple antibodies have been developed [5].…”

Section: Introductionmentioning

confidence: 99%

Efficacy of the combination of BRII-196/BRII-198 in the treatment of COVID-19 vaccine breakthrough infections

Guo

2024

Am J Transl Res

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Background: are two recombinant human immunoglobulin (Ig) G1 monoclonal antibodies (mAbs) that non-competitively target distinct epitope regions within the receptor-binding domain (RBD) of the coronavirus spike glycoproteins. These antibodies are derived directly from human B cells of individuals who recovered from COVID-19. Objective: To analyze the efficacy of in the treatment of coronavirus disease 2019 (COVID-19) vaccine breakthrough infections. Methods: COVID-19 patients at high risk of progressing to severe and critical illness, with an initial SARS-CoV-2 immunoglobulin (Ig) G antibody level < 1.0 S/CO (detected within 24-48 hours post COVID-19 diagnosis), were treated with BRII-196/BRII-198 within three days of symptom onset. Treatment continued until the antibody level exceeded 1.0 S/CO. Patients whose absolute lymphocyte count (ALC) at first detection (within 24-48 h post-diagnosis) was < 0.8 × 10 9 /L received thymalfasin therapy within three days of symptom onset, continuing until the ALC level surpassed 0.8 × 10 9 /L. We determined the correlation of SARS-CoV-2 IgG antibody level and ALC with the condition of COVID-19 patients. Additionally, we analyzed the effects of BRII-196/BRII-198 on SARS-CoV-2 nucleic acid (NA) negative conversion, lymphocyte count recovery, and the change in SARS-CoV-2 IgG antibody level from the first positive NA test for SARS-CoV-2 to negative conversion in COVID-19 patients. Results: A total of 61 cases of breakthrough infections were observed, classified as 10 mild cases, 31 ordinary cases, and 20 severe cases. Among these, 20%, 48.4% and 75% of the patients with mild, ordinary, and severe COVID-19, respectively, had initial SARS-CoV-2 IgG antibody level < 1.0 S/CO. Additionally, 0%, 35% and 70% had initial ALC < 0.8 × 10 9 /L, respectively. Fifteen ordinary and 15 severe COVID-19 patients were treated with In severely infected patients, BRII-196/BRII-198 treatment showed statistically significant differences in NA negative conversion time and changes in SARS-CoV-2 IgG antibody levels (P < 0.05). However, in patients classified with ordinary severity, BRII-196/BRII-198 treatment did not lead to notable differences in NA negative conversion time or changes in SARS-CoV-2 IgG antibody level (P > 0.05). BRII-196/BRII-198 therapy was not associated with lymphocyte count recovery time in patients with either ordinary and/or severe COVID-19 (P > 0.05). Conclusions: The initial levels of SARS-CoV-2 IgG antibody and lymphocytes in fully vaccinated patients with breakthrough infections are inversely correlated with the severity of the disease. Early treatment with BRII-196/ BRII-198 can shorten NA negative conversion time in severe COVID-19 patients and increase in vivo neutralizing antibody levels post-conversion, providing lasting protection. However, BRII-196/BRII-198 does not influence lymphocyte count recovery in patients with either ordinary and/or severe COVID-19.

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“…Both mAbs have a triple amino acid substitution, M257Y/S259T/T261E, in the fragment crystallizable region to prolong the half-life ( 16 , 17 ) and reduce binding activity against Fcγ receptors, potentially minimizing risk for antibody-dependent enhancement ( 12 , 13 ). Phase 1 studies investigating the safety, tolerability, and pharmacokinetics of intravenous amubarvimab (NCT04479631) and romlusevimab (NCT04479644) ( 12 , 13 ) supported further clinical evaluation ( 18 ). We report the results of a phase 2 and 3 trial of amubarvimab plus romlusevimab in nonhospitalized persons with mild to moderate COVID-19 at high risk for progression to severe disease.…”

mentioning

confidence: 99%