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A Phase 2/3 study of S-217622 in participants with SARS-CoV-2 infection

A Phase 2/3 study of S-217622

2923

Phase 2a Part: In the ITT population, the propotion of male participants was 42.9% (6/14 participants) in the 375/125 mg group, 50.0% (6/12 participants) in the 750/250 mg group, and 78.6% (11/14 participants) in the placebo group, respectively, with the placebo group having a higher number of male participants. The median age (range) was 34.5 (22-59) years, 37.5 (23-63) years, and 35.0 (16-61) years, respectively, with similar trends among the groups. Phase 2b Part: In the ITT1 population, the proportion of male participants was 53.5% (61/114 participants) in the 375/125 mg group, 56.9% (66/116 participants) in the 750/250 mg group, and 64.9% (72/111 participants) in the placebo group, respectively, with the placebo group having a higher number of male participants. The median age (range) was 32.0 (14-68) years, 34.0 (12-69) years, and 37.0 (16-68) years, respectively, and was similar among the groups. Phase 3 Part: In the ITT population with < 72 hours from the onset of COVID-19 to randomization, the proportion of male participants was 55.6% (193/347 participants) and 50.7% (174/343 participants). The median age (range) was 34.0 (14-67) years and 32.0 (12-68) years, respectively. Phase 2b/3 Part: In the ITT population, the proportion of male participants was 56.2% (109/194 participants) in the 375/125 mg group and 54.5% (103/189 participants) in the placebo group, respectively. The median age (range) was 38.0 (13-69) years and 38.0 (12-69) years, respectively.

Phase 2a Part: A total of 69 participants, including 60 with mild/moderate SARS-CoV-2 infection and 9 with asymptomatic SARS-CoV-2 infection, were randomized in a 1:1:1 ratio to the 375/125 mg group, the 750/250 mg group, and the placebo group. The ITT population, which is the primary analysis population for efficacy, comprised 47 participants (40 [14, 12, 14] with mild/moderate SARS-CoV-2 infection and 7 [2, 2, 3] with asymptomatic SARS-CoV-2 infection). The mITT population, the primary analysis population for efficacy, consisted of 43 participants excluding 4 from the ITT (37 [13, 12, 12] with mild/moderate SARS-CoV-2 infection and 6 [2, 2, 2] with asymptomatic SARS-CoV-2 infection). Phase 2b Part: A total of 428 participants with mild/moderate SARS-CoV-2 infection were randomized in a 1:1:1 ratio to the 375/125 mg group, the 750/250 mg group, and the placebo group. The ITT1 population, the primary analysis population for efficacy, comprised 341 participants (114, 116, 111). Phase 3 Part: A total of 1821 participants with mild/moderate SARS-CoV-2 infection were randomized in a 1:1:1 ratio to the 375/125 mg group, the 750/250 mg group, and the placebo group. The ITT population comprised 1798 participants (603, 595, 600). The ITT population with population with < 72 hours from the onset of COVID-19 to randomization, which is the primary analysis population, comprised 347 participants in the 375/125 mg group and 343 participants in the placebo group. Phase 2b/3 Part: A total of 605 participants with asymptomatic/mild symptoms only SARS-CoV-2 infections were randomized in a 1:1:1 ratio to the 375/125 mg group, the 750/250 mg group, and the placebo group. The ITT population comprised 572 participants (194, 189, 189).

Phase 2a, 2b, 3 Parts marged analysis: A total of 2288 participants (763 in the 375/125 mg group, 759 in the 750/250 mg group, and 766 in the placebo group) were included in the safety analysis population. No deaths were reported and all other serious TEAEs which occurred in 1 participant in the 375/125 mg group and 3 participants in the placebo group were considered unrelated to the study intervention. TEAEs leading to discontinuation of study intervention were reported in 6 participants of the 375/125 mg group, 6 participants of the 750/250 mg group, and 2 participants of the placebo group. Of those, 5 events in the 375/125 mg group, 2 events in the 750/250 mg group, and 2 events in the placebo group were considered related to the study intervention, but all these events were resolved or resolving after discontinuation of study intervention. Phase 2b/3 Part: A total of 604 participants (201 in the 375/125 mg group, 202 in the 750/250 mg group, 201 in the placebo group) were included in the safety analysis population. No deaths were reported in any of the intervention groups. Other serious TEAEs were reported in 2 participants in the 750/250 mg group, both of which were considered unrelated to the study intervention. TEAEs leading to discontinuation of study intervention were reported in 1 participant in the 375/125 mg group and 2 participants in the 750/250 mg group. Of these events, 1 event in each the 375/125 mg group and the 750/250 mg group was considered related to the study intervention and was resolved or resolving after the discontinuation of study intervention.

The main efficacy results in Phase 2a, 2b, 3 Parts are shown as below. Phase 2a Part: In the mITT population, the means (SDs) of the changes from baseline in viral titer (log10 [TCID50/mL]) were -1.05 (1.17), -2.03 (1.21), and -0.86 (0.93) in the 375/125 mg group, the 750/250 mg group, and the placebo group, respectively on Day 2, -2.42 (1.42), -2.81 (1.21), and -1.54 (0.74) on Day 4, and -2.56 (1.35), -2.76 (1.19), and -2.08 (0.91) on Day 6. The change from baseline in viral titer was significant in the 750/250 mg group compared to the placebo group at Days 2 and 4 (p=0.0212 and p=0.0083, respectively). Phase 2b Part: In the ITT1 population, the means (SDs) of the time-weighted average changes in total score of 12 COVID-19 symptoms from Day 1 up to Day 6 were -5.95 (4.02), -5.42 (3.70), and -4.92 (3.25) in the 375/125 mg group, the 750/250 mg group, and the placebo group, respectively. No significant difference was indicated in the 375/125 mg group or the 750/250 mg group compared with the placebo group. The LS means of the changes were greater in both the 375/125 mg group and the 750/250 mg group compared with the placebo group. The LS means of the changes in SARS-CoV-2 viral titer on Day 4 decreased by approximately 0.4 log10 (TCID50/mL) in the 375/125 mg group and the 750/250 mg group compared with the placebo group, and a significant difference was indicated in both the 375/125 mg group and the 750/250 mg group compared with the placebo group (p<0.0001). Phase 3 Part: In the ITT population with < 72 hours from the onset of COVID-19 to randomization, the time to resolution of 5 COVID-19 symptoms as median (95% CI) was 167.9 (145.0, 197.6) hours in the 375/125 mg group and 192.2 (174.5, 238.3) hours in the placebo group. A statistically significant difference was shown (stratified Peto-Prentice's generalized Wilcoxon test; one-sided p=0.0204)

In this study, S-217622 demonstrated an antiviral effect and improvement of clinical symptoms, and no notable safety concern was identified.

Mar. 04, 2025

Sept. 13, 2022

https://journals.asm.org/doi/10.1128/aac.00697-22

Yes

Individual patients data will be shared according to the Clinical Trial Data Transparency Policy of Shionogi (http://www.shionogi.co.jp/en/company/policy/cl inical-trial.html). Requests from researchers will be reviewed by an Independent Review Panel, consisting of third-party experts, with regard to the validity and feasibility of the research that the researchers intend to carry out. When the request is approved by the panel, the researchers will be requested to execute a contract (which will have certain requirements with respect to personal data privacy, confidentiality, and compliance with the law) with Shionogi before being provided with access to the clinical trial data. Individual patient data will be shared after anonymization in order to protect the privacy of study participants and to comply with laws and regulations (including but not limited to the terms of the patient informed consent forms).

https://jrct.mhlw.go.jp/latest-detail/jRCT2031210350

Gomez JuanCarlos

Shionogi & Co., Ltd.

1-8, Doshomachi 3-chome, Chuo-ku, Osaka, Osaka

shionogiclintrials-admin@shionogi.co.jp

Corporate Communications Department

Shionogi & Co., Ltd.

1-8, Doshomachi 3-chome, Chuo-ku, Osaka, Osaka

+81-6-6209-7885

shionogiclintrials-admin@shionogi.co.jp

Complete

Sept. 27, 2021

Interventional

randomized controlled trial

double blind

placebo control

parallel assignment

treatment purpose

For mild/moderate SARS-CoV-2-infected participants:
- Participants who were diagnosed as SARS-CoV-2 positive within 120 hours before randomization.
- Participants with time from COVID-19 onset to randomization of =< 120 hours.
- Participants who have at least one moderate or severe symptom among the following 12 symptoms of COVID-19 at the time of randomization.
(low energy or tiredness, muscle or body aches, headache, chills or shivering, feeling hot or feverish, stuffy or runny nose, sore throat, cough, shortness of breath, nausea, vomiting, diarrhea)
For asymptomatic SARS-CoV-2-infected participants (Phase 2a Part):
- Participants who were diagnosed as SARS-CoV-2 positive within 120 hours before randomizationt.
- Participants who have none of the following 14 symptoms of COVID-19 within 2 weeks before randomization.
(low energy or tiredness, muscle or body aches, headache, chills or shivering, feeling hot or feverish, taste disorder, smell disorder, stuffy or runny nose, sore throat, cough, shortness of breath, nausea, vomiting, diarrhea)
For asymptomatic/only mild symptoms SARS-CoV-2-infected participants (Phase 2b/3 Part):
- Participants who were diagnosed as SARS-CoV-2 positive within 120 hours before randomizationt.
- Participants who do not have any symtoms of moderate or severe symptom among the 12 symptoms of COVID-19 at the time of randomization.

Common for Phase 2a Part and Phase 2b/3 Part
And commmon for mild/moderate and asumptomatic SARS-CoV-2-infected participants
- Participants with a percutaneous oxygen saturation (SpO2) during wakefulness of =< 93% (room air)
- Participants strongly suspected to have pneumonia
- Participants who need oxygen administration
- Participants who need a mechanical ventilation
- Participants who are strongly suspected to have worsening of symptoms of SARS-CoV-2 infection within 48 hours after randomization, in the opinion of the investigator/subinvestigator
- Participants with suspected active and systemic infections requiring treatment at the time of randomization (excluding SARS-CoV-2)
- Current or chronic history of moderate or severe liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
- Current or chronic history of moderate or severe kidney disease
- Participants who have used any of the following drugs within 7 days prior to randomization
(approved/unapproved drugs for the treatment of SARS-CoV-2 infection, antiviral, antibacterial, or antifungal drugs [excluding topical use])
- Participants who have used any of the following drugs within 14 days prior to randomization
(strong CYP 3A inhibitor, strong CYP 3A inducer, products containing St. John's wort)

Both

COVID-19

S-217622
Oral administration of S-217622 tablet once daily for 5 days (5 times in total)
Placebo
Oral administration of placebo tablet once daily for 5 days (5 times in total)

Phase 2a Part
Change from baseline in SARS-CoV-2 viral titer at each time point
Phase 2b Part
Time-weighted average change in total score of 12 COVID-19 symptoms from Day 1 up to Day 6
Change from baseline on Day 4 in SARS-CoV-2 viral titer
Phase 3 Part
Time to resolution of 5 COVID-19 symptoms
Change from baseline on Day 4 in the amount of SARS-CoV-2 viral RNA
Time to the first negative SARS CoV-2 viral titer
Phase 2b/3 Part
Primary endpoint and key secondary endpoint are not set.

+81-3-5491-4478

Sept. 10, 2021

Republic of Korea/Republic of Singapore/Socialist Republic of Vietnam