One Week of Oral Camostat Versus Placebo in Nonhospitalized Adults With Mild-to-Moderate Coronavirus Disease 2019 (COVID-19): A Randomized Controlled Phase 2 Trial
et al., Clinical Infectious Diseases, doi:10.1093/cid/ciad342, ACTIV-2, NCT04518410, Jun 2023
RCT 216 patients, 55% >5 days from symptom onset, showing no significant difference with camostat treatment. Longer-term mortality results are from the registry and are not shown in the paper.
Standard of Care (SOC) for COVID-19 in the study country,
the USA, is very poor with very low average efficacy for approved treatments1.
Only expensive, high-profit treatments were approved for early treatment. Low-cost treatments were excluded, reducing the probability of early treatment due to access and cost barriers, and eliminating complementary and synergistic benefits seen with many low-cost treatments.
Study covers TMPRSS2 inhibitors and camostat.
|
risk of death, 0.9% lower, RR 0.99, p = 1.00, treatment 1 of 106 (0.9%), control 1 of 105 (1.0%), NNT 11130, clinical trials registry.
|
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risk of death, 198.2% higher, RR 2.98, p = 1.00, treatment 1 of 109 (0.9%), control 0 of 107 (0.0%), continuity correction due to zero event (with reciprocal of the contrasting arm), day 28.
|
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risk of hospitalization, 17.8% higher, RR 1.18, p = 1.00, treatment 6 of 109 (5.5%), control 5 of 107 (4.7%), day 28.
|
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risk of progression, 10.3% lower, RR 0.90, p = 0.11, treatment 85 of 109 (78.0%), control 93 of 107 (86.9%), NNT 11, Table S6.
|
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no improvement, 13.4% lower, RR 0.87, p = 0.70, treatment 15 of 109 (13.8%), control 17 of 107 (15.9%), NNT 47, no improvement, day 28.
|
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recovery time, no change, relative time 1.00, p = 0.99, treatment 109, control 107.
|
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risk of no recovery, 14.3% lower, RR 0.86, p = 0.48, treatment 109, control 107, time to all targeted symptoms absent for 4 days, Table S6.
|
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risk of no recovery, 14.3% lower, RR 0.86, p = 0.84, treatment 109, control 107, time to return to usual health for 2 days, Table S6.
|
|
risk of no recovery, no change, RR 1.00, p = 0.47, treatment 109, control 107, time to return to usual health for 4 days, Table S6.
|
|
risk of no recovery, 8.3% lower, RR 0.92, p = 0.76, treatment 109, control 107, time-averaged total daily symptom score, Table S6.
|
| Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates |
Jilg et al., 5 Jun 2023, Randomized Controlled Trial, placebo-controlled, USA, peer-reviewed, median age 37.0, 39 authors, trial NCT04518410 (history) (ACTIV-2).
One Week of Oral Camostat Versus Placebo in Nonhospitalized Adults With Mild-to-Moderate Coronavirus Disease 2019: A Randomized Controlled Phase 2 Trial
Clinical Infectious Diseases, doi:10.1093/cid/ciad342
Background. Camostat inhibits severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in vitro. We studied the safety and efficacy of camostat in ACTIV-2/A5401, a phase 2/3 platform trial of therapeutics for COVID-19 in nonhospitalized adults. Methods. We conducted a phase 2 study in adults with mild-to-moderate COVID-19 randomized to oral camostat for 7 days or a pooled placebo arm. Primary outcomes were time to improvement in COVID-19 symptoms through day 28, proportion of participants with SARS-CoV-2 RNA below the lower limit of quantification (LLoQ) from nasopharyngeal swabs through day 14, and grade ≥3 treatment-emergent adverse events (TEAEs) through day 28. Results. Of 216 participants (109 randomized to camostat, 107 to placebo) who initiated study intervention, 45% reported ≤5 days of symptoms at study entry and 26% met the protocol definition of higher risk of progression to severe COVID-19. Median age was 37 years. Median time to symptom improvement was 9 days in both arms (P = .99). There were no significant differences in the proportion of participants with SARS-CoV-2 RNA <LLoQ on days 3, 7, and 14. Through day 28, 6 (5.6%) participants in the camostat arm and 5 (4.7%) in the placebo arm were hospitalized; 1 participant in the camostat arm subsequently died. Grade ≥3 TEAEs occurred in 10.1% of camostat versus 6.5% of placebo participants (P = .35). Conclusions. In a phase 2 study of nonhospitalized adults with mild-to-moderate COVID-19, oral camostat did not accelerate viral clearance or time to symptom improvement, or reduce hospitalizations or deaths. Clinical Trials Registration. ClinicalTrials.
Age Median age (Q1, Q3), y 37 (29, 49) 39 (29, 48) 37 (29, 48) ≥ 60 y, n (%) 3 (3) 8 (7) 11 (5) Female sex, n (%) 63 ( 58 Gamma, n (%) 11 Delta, n (%) 1 (1) 0 (0) Consisting of data provided by the authors to benefit the reader, the posted materials are not copyedited and are the sole responsibility of the authors, so questions or comments should be addressed to the corresponding author.
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"abstract": "<jats:title>Abstract</jats:title>\n <jats:sec>\n <jats:title>Background</jats:title>\n <jats:p>Camostat inhibits severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in vitro. We studied the safety and efficacy of camostat in ACTIV-2/A5401, a phase 2/3 platform trial of therapeutics for COVID-19 in nonhospitalized adults.</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Methods</jats:title>\n <jats:p>We conducted a phase 2 study in adults with mild-to-moderate COVID-19 randomized to oral camostat for 7 days or a pooled placebo arm. Primary outcomes were time to improvement in COVID-19 symptoms through day 28, proportion of participants with SARS-CoV-2 RNA below the lower limit of quantification (LLoQ) from nasopharyngeal swabs through day 14, and grade ≥3 treatment-emergent adverse events (TEAEs) through day 28.</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Results</jats:title>\n <jats:p>Of 216 participants (109 randomized to camostat, 107 to placebo) who initiated study intervention, 45% reported ≤5 days of symptoms at study entry and 26% met the protocol definition of higher risk of progression to severe COVID-19. Median age was 37 years. Median time to symptom improvement was 9 days in both arms (P = .99). There were no significant differences in the proportion of participants with SARS-CoV-2 RNA &lt;LLoQ on days 3, 7, and 14. Through day 28, 6 (5.6%) participants in the camostat arm and 5 (4.7%) in the placebo arm were hospitalized; 1 participant in the camostat arm subsequently died. Grade ≥3 TEAEs occurred in 10.1% of camostat versus 6.5% of placebo participants (P = .35).</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Conclusions</jats:title>\n <jats:p>In a phase 2 study of nonhospitalized adults with mild-to-moderate COVID-19, oral camostat did not accelerate viral clearance or time to symptom improvement, or reduce hospitalizations or deaths.</jats:p>\n <jats:p>Clinical Trials Registration. ClinicalTrials.gov identifier: NCT 04518410.</jats:p>\n </jats:sec>",
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Late treatment
is less effective
is less effective
jilg