Peginterferon lambda for the treatment of hospitalized patients with mild COVID-19: A pilot phase 2 randomized placebo-controlled trial

Kim et al., Frontiers in Medicine, doi:10.3389/fmed.2023.1095828, NCT04343976, Feb 2023

https://c19early.org/kim9.html

Very small RCT with 14 hospitalized patients in the USA showing no significant differences with peginterferon lambda. Viral load was improved, however 86% of treatment versus 14% of control patients received remdesivir, and the median baseline viral load for treatment patients was 3.6 log10 copies/ml versus 0 for control.

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. Low-cost treatments were excluded, reducing the probability of treatment—especially early—due to access and cost barriers, and eliminating complementary and synergistic benefits seen with many low-cost treatments.

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risk of ICU admission, 200.0% higher, RR 3.00, p = 1.00, treatment 1 of 7 (14.3%), control 0 of 7 (0.0%), continuity correction due to zero event (with reciprocal of the contrasting arm).

hospitalization time, 25.0% higher, relative time 1.25, p = 0.59, treatment median 5.0 IQR 4.0 n=7, control median 4.0 IQR 5.0 n=7.

risk of no viral clearance, 12.5% lower, RR 0.88, p = 1.00, treatment 3 of 6 (50.0%), control 4 of 7 (57.1%), NNT 14, day 14.

risk of no viral clearance, 66.7% higher, RR 1.67, p = 0.59, treatment 5 of 7 (71.4%), control 3 of 7 (42.9%), day 7.

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1. c19early.org, c19early.org/soc/usa.html.c19early.org/soc/usa.html.

Kim et al., 24 Feb 2023, Single Blind Randomized Controlled Trial, placebo-controlled, USA, peer-reviewed, median age 54.0, 9 authors, study period 14 July, 2020 - 16 July, 2021, trial NCT04343976 (history). Contact: chung.raymond@mgh.harvard.edu.

This Paper Peg.. Lambda All

Peginterferon lambda for the treatment of hospitalized patients with mild COVID-19: A pilot phase 2 randomized placebo-controlled trial

Myung-Ho Kim, Josh Elbaz, Nikolaus Jilg, Jenna L Gustafson, Min Xu, Dilara Hatipoglu, Eric Nohelty, Arthur Y Kim, Raymond T Chung

Frontiers in Medicine, doi:10.3389/fmed.2023.1095828

Background: This study aimed to investigate the efficacy and safety of subcutaneous injection of peginterferon lambda in patients hospitalized with COVID-19. Methods: In this study (NCT04343976), patients admitted to hospital with COVID-19 confirmed by RT-PCR from nasopharyngeal swab were randomly assigned within 48 h to receive peginterferon lambda or placebo in a 1:1 ratio. Participants were subcutaneously injected with a peginterferon lambda or saline placebo at baseline and day 7 and were followed up until day 14. Results: We enrolled 14 participants; 6 participants (85.7%) in the peginterferon lambda group and 1 participant (14.3%) in the placebo group were treated with remdesivir prior to enrollment. Fifty percent of participants were SARS-CoV-2 RNA negative at baseline although they tested SARS-CoV-2 RNA positive within 48 h of randomization. Among participants who were SARS-CoV-2 positive at baseline, 2 out of 5 participants (40%) in the peginterferon lambda group became negative at day 14, while 0 out of 2 participants (0%) in the placebo group achieved negativity for SARS-CoV-2 by day 14 (p > 0.05). The median change in viral load (log copies per ml) was +1.72 (IQR −2.78 to 3.19) in the placebo group and −2.22 (IQR −3.24 to 0.55) in the peginterferon lambda group at day 14 (p = 0.24). Symptomatic changes did not differ between the two groups. Peginterferon lambda was well tolerated with a few treatment-related adverse effects. Conclusion: Peginterferon lambda appears to accelerate SARS-CoV-2 viral load decline and improve plasma disease progression markers in hospitalized patients with COVID-19.

Results We enrolled 14 participants admitted to the Massachusetts General Hospital and with COVID-19 between July 14, 2020 and July 16, 2021. The median age was 54.0 (IQR 45.50 to 58.50), 11 participants (78.6%) were male, and 9 (64.3%) were Hispanic (Table 1 ; Supplementary Table 1 ). All 14 randomly assigned participants were initially injected with a placebo or peginterferon lambda within a median of 43.1 h (IQR 35.8 to 48.4) after testing SARS-CoV-2 positive. Thirteen participants (92.9%) completed 14 days of follow up with 1 participant in the placebo group lost to follow up after day 7 (Figure 1 ). The median baseline SARS-CoV-2 viral load was 1.38 log copies per ml (IQR 0.00 to 4.23), with 5 participants (71.4%) in the placebo group and 2 participants (28.6%) in the peginterferon lambda group having undetectable viral load on the day of randomization although they were tested SARS-CoV-2 RNA positive within 48 h of randomization. The median sum of symptom scores was 2.00 (IQR 0.00 to 4.00) in the placebo group and 5.50 (IQR 2.75 to 7.50) in the peginterferon lambda group. Six participants (85.7%) in the peginterferon lambda group and Ethics statement The studies involving human participants were reviewed and approved by Massachusetts General Hospital. The patients/participants provided their written informed consent to participate in this study. Author contributions MHK, NJ, AK, and RC contributed to study conception and design. MHK, JE, JG, and EN contributed to..

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DOI record: { "DOI": "10.3389/fmed.2023.1095828", "ISSN": [ "2296-858X" ], "URL": "http://dx.doi.org/10.3389/fmed.2023.1095828", "abstract": "BackgroundThis study aimed to investigate the efficacy and safety of subcutaneous injection of peginterferon lambda in patients hospitalized with COVID-19.MethodsIn this study (NCT04343976), patients admitted to hospital with COVID-19 confirmed by RT-PCR from nasopharyngeal swab were randomly assigned within 48 h to receive peginterferon lambda or placebo in a 1:1 ratio. Participants were subcutaneously injected with a peginterferon lambda or saline placebo at baseline and day 7 and were followed up until day 14.ResultsWe enrolled 14 participants; 6 participants (85.7%) in the peginterferon lambda group and 1 participant (14.3%) in the placebo group were treated with remdesivir prior to enrollment. Fifty percent of participants were SARS-CoV-2 RNA negative at baseline although they tested SARS-CoV-2 RNA positive within 48 h of randomization. Among participants who were SARS-CoV-2 positive at baseline, 2 out of 5 participants (40%) in the peginterferon lambda group became negative at day 14, while 0 out of 2 participants (0%) in the placebo group achieved negativity for SARS-CoV-2 by day 14 (p &gt; 0.05). The median change in viral load (log copies per ml) was +1.72 (IQR −2.78 to 3.19) in the placebo group and −2.22 (IQR −3.24 to 0.55) in the peginterferon lambda group at day 14 (p = 0.24). Symptomatic changes did not differ between the two groups. Peginterferon lambda was well tolerated with a few treatment-related adverse effects.ConclusionPeginterferon lambda appears to accelerate SARS-CoV-2 viral load decline and improve plasma disease progression markers in hospitalized patients with COVID-19.", "alternative-id": [ "10.3389/fmed.2023.1095828" ], "author": [ { "affiliation": [], "family": "Kim", "given": "Myung-Ho", "sequence": "first" }, { "affiliation": [], "family": "Elbaz", "given": "Josh", "sequence": "additional" }, { "affiliation": [], "family": "Jilg", "given": "Nikolaus", "sequence": "additional" }, { "affiliation": [], "family": "Gustafson", "given": "Jenna L.", "sequence": "additional" }, { "affiliation": [], "family": "Xu", "given": "Min", "sequence": "additional" }, { "affiliation": [], "family": "Hatipoglu", "given": "Dilara", "sequence": "additional" }, { "affiliation": [], "family": "Nohelty", "given": "Eric", "sequence": "additional" }, { "affiliation": [], "family": "Kim", "given": "Arthur Y.", "sequence": "additional" }, { "affiliation": [], "family": "Chung", "given": "Raymond T.", "sequence": "additional" } ], "container-title": "Frontiers in Medicine", "container-title-short": "Front. 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Late treatment
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