Opaganib in Coronavirus Disease 2019 Pneumonia: Results of a Randomized, Placebo-Controlled Phase 2a Trial
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Abstract
Background
Opaganib, an oral sphingosine kinase-2 inhibitor with antiviral and anti-inflammatory properties, was shown to inhibit severe acute respiratory syndrome coronavirus 2 replication in vitro. We thus considered that opaganib could be beneficial for moderate to severe coronavirus disease 2019 (COVID-19) pneumonia. The objective of the study was to evaluate the safety of opaganib and its effect on supplemental oxygen requirements and time to hospital discharge in COVID-19 pneumonia hospitalized patients requiring supplemental oxygen.
Methods
This Phase 2a, randomized, double-blind, placebo-controlled study was conducted between July and December 2020 in 8 sites in the United States. Forty-two enrolled patients received opaganib (n = 23) or placebo (n = 19) added to standard of care for up to 14 days and were followed up for 28 days after their last dose of opaganib/placebo.
Results
There were no safety concerns arising in this study. The incidence of ≥Grade 3 treatment-emergent adverse events was 17.4% and 33.3% in the opaganib and placebo groups, respectively. Three deaths occurred in each group. A numerical advantage for opaganib over placebo was observed in in this nonpowered study reflected by total supplemental oxygen requirement from baseline to Day 14, the requirement for supplemental oxygen for at least 24 hours by Day 14, and hospital discharge.
Conclusions
In this proof-of-concept study, hypoxic, hospitalized patients receiving oral opaganib had a similar safety profile to placebo-treated patients, with preliminary evidence of benefit for opaganib as measured by supplementary oxygen requirement and earlier hospital discharge. These findings support further evaluation of opaganib in this population.
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Bin Cao, Lianhan Shang
Review 1: "Opaganib in COVID-19 pneumonia: Results of a randomized, placebo-controlled Phase 2a trial"
Reviewers: Bin Cao (China-Japan Friendship Hospital) and Lianhan Shang | 📒📒📒 ◻️◻️
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Bin Cao, Lianhan Shang
Review of "Opaganib in COVID-19 pneumonia: Results of a randomized, placebo-controlled Phase 2a trial"
Reviewers: Bin Cao (China-Japan Friendship Hospital) and Lianhan Shang | 📒📒📒 ◻️◻️
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SciScore for 10.1101/2021.08.23.21262464: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics not detected. Sex as a biological variable not detected. Randomization Design: This was a Phase 2a, proof-of-concept, multi-center, randomized, double-blind, parallel arm, placebo-controlled study conducted in eight sites in the USA. Blinding Treatment assignments remained blinded to the patients, investigators, hospital staff, and sponsor (RedHill Biopharma). Power Analysis not detected. Table 2: Resources
No key resources detected.
Results 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: We detected the following sentences addressing limitations in the study:Lim…
SciScore for 10.1101/2021.08.23.21262464: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics not detected. Sex as a biological variable not detected. Randomization Design: This was a Phase 2a, proof-of-concept, multi-center, randomized, double-blind, parallel arm, placebo-controlled study conducted in eight sites in the USA. Blinding Treatment assignments remained blinded to the patients, investigators, hospital staff, and sponsor (RedHill Biopharma). Power Analysis not detected. Table 2: Resources
No key resources detected.
Results 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: We detected the following sentences addressing limitations in the study:Limitations: The main limitation of this study is its small sample size, allowing for descriptive analyses rather than meaningful statistical interpretation. A further limitation was the imbalance in supplemental oxygen requirement at baseline, a result of the small sample size despite randomization. Nonetheless, the results suggest a potential clinical benefit for opaganib compared to placebo. An additional limitation of the study is that certain pre-defined secondary endpoints that relied on inpatient data collection could not be assessed. This was due to changing standard of practice leading to earlier discharge of patients than was anticipated at the time of protocol development. Notably, a greater proportion of patients on opaganib versus placebo were discharged prior to Day 14. Lastly, the clinical interpretation of the primary endpoint was limited, as described above, leading to the addition of post-hoc analyses to help with the overall interpretation of the data.
Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT04414618 Completed A Study of Opaganib in Coronavirus Disease 2019 Pneumonia NCT04467840 Completed Opaganib, a Sphingosine Kinase-2 (SK2) Inhibitor in COVID-19… 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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