Clinical trial NCT05506176: A Clinical Study to Evaluate the Efficacy and Safety of SIM0417 Orally Co-Administered With Ritonavir in Symptomatic Adult Participants With Mild to Moderate COVID-19
Official title: A Multicenter, Randomized, Double-blind, Phase Ⅱ/Ⅲ Clinical Study to Evaluate the Efficacy and Safety of SIM0417 Orally Co-Administered With Ritonavir in Symptomatic Adult Participants With Mild to Moderate COVID-19
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: COVID-19
Keywords: Mild to Moderate COVID-19
Lead sponsor: Jiangsu Simcere Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2022-08-18
Enrollment: 1208
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This Phase Ⅱ/Ⅲ study is to evaluate whether or not there is a difference in time recovery of COVID-19 signs and symptoms through Day 29 between SIM0417/ritonavir and placebo.

Detailed description: The efficacy, safety, and tolerability of SIM0417/ritonavir compared to placebo will be investigated. The exposure to SIM0417 in this population will also be investigated.

Eligibility criteria: Inclusion Criteria:

1. Participants ≥18 years of age (or the minimum country-specific age of consent if \>18) at the time of signing the informed consent/assent form.
2. Initial positive SARS-CoV-2 tested by RT-PCR or rapid antigen test within 5 days (120 h) prior to the first dose of study drug collected from any respiratory tract specimen (e.g., oropharyngeal, NP or nasal swab, or saliva).
3. Initial onset of signs/symptoms attributable to COVID-19 within 3 days prior to the day of the first dose of study drug. The onset time of symptoms was defined as the time when body temperature first rose; or the onset of any of these COVID-19 symptoms.
4. At least one of the following symptoms of COVID-19 present within 24 hours prior to the first dose of study drug and meeting severity.
5. Has mild or moderate COVID-19.
6. Participants agree to take highly effective contraceptive measures from signing the informed consent to at least 1 month after the last dose of study intervention.
7. Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
8. Willing and able to provide written informed consent, or with a legal representative who can provide informed consent.

Exclusion Criteria:

1. Urgent or expected need for nasal high-flow oxygen therapy or positive pressure ventilation, invasive mechanical ventilation or Extracorporeal membrane oxygenation(ECMO).
2. Known medical history of active liver disease (other than nonalcoholic hepatic steatosis), including acute or chronic active hepatitis B or C infection, primary biliary cirrhosis, Child-Pugh Class B or C, or acute liver failure.
3. Receiving dialysis or have known moderate to severe renal impairment (ie, eGFR \<45 mL/min/1.73 m2 within 6 months of the screening visit, using the serum creatinine-based CKD-EPI formula).
4. Compromised immune system (including patients receiving long-term immunosuppressant therapy, or those with progressed or relapsed cancer or human immunodeficiency virus \[HIV\] infection).
5. Moderate to severe congestive heart failure (New York Heart Association class III or IV) within 6 months prior to Screening, recent (within the past 6 months prior to Screening) cerebrovascular accident, myocardial infarction, coronary artery stenting, or uncontrolled hypertension (defined as documented systolic blood pressure \> 160 mmHg or diastolic blood pressure \> 100 mmHg).
6. Acute episode of chronic respiratory diseases, including bronchial asthma, chronic obstructive pulmonary disease.
7. Suspected or confirmed concurrent active systemic infection other than COVID-19 (eg, co-infected with influenza) that may interfere with the evaluation of response to the study intervention.
8. Any comorbidity requiring surgery within 14 days prior to study entry, or that is considered life-threatening within 30 days prior to study entry, as determined by the investigator.
9. Has hypersensitivity or other contraindication to any of the components of the study interventions.
10. Other medical or psychiatric conditions including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
11. Clinical signs indicative of severe systemic illness with COVID-19, such as respiratory rate ≥30 per minute, heart rate ≥125 per minute, oxygen saturation (SpO2) of ≤93% on room air or the ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2) \<300 obtained at rest within 24 hours prior to randomization.
12. Treatment with antivirals against SARS-CoV-2 within 14 days prior to the first dose of randomization.
13. Current or expected use of any medications or substances that are highly dependent on CYP3A4 for clearance and for which elevated plasma concentrations may be associated with serious and/or life-threatening events during study treatment and for 4 days after the last dose of study drug (refer to Appendix 6).
14. Concomitant use of any medications or substances that are strong inducers of CYP3A4 are prohibited within 21 days prior to randomization and during study treatment (refer to Appendix 6).
15. Has received (within the past 30 days or 5 × drug half-life prior to randomization, which is longer) or is expected to receive COVID-19 monoclonal antibody or convalescent COVID-19 plasma during study treatment.
16. Systemic glucocorticoid therapy (prednisone ≥ 20 mg/day or equivalent doses of other steroids) for at least 14 consecutive days within 30 days prior to randomization.
17. Has received any SARS-CoV-2 vaccine within 3 months prior to randomization.
18. Participating in another interventional clinical study with an investigational compound or device, including those for COVID-19.
19. Previous administration with any investigational drug or vaccine within 30 days (or as determined by the local requirement) or 5 half-lives (whichever is longer) prior to randomization.
20. Known prior participation in this trial or other trial involving SIM0417.
21. Women who are breastfeeding or have a positive pregnancy test in the pre-dose examinations. The following female patients who have documentation of either a or b below do not need to undergo a pregnancy test in the pre-dose examinations:

    1. Postmenopausal women (defined as cessation of regular menstrual periods for 12 months or more, and confirmed by a follicle-stimulating hormone test if \<60 years old)
    2. Women who are surgically sterile by hysterectomy, bilateral oophorectomy, or tubal ligation
22. Has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant or that could prevent, limit, or confound the protocol-specified assessments.

    For subjects who have conditional ECG at screening only:
23. Clinically relevant or significant electrocardiographic abnormalities (e.g., second-degree type II AV block, left bundle branch block, etc.), including electrocardiographic QT interval corrected for heart rate using Fridericia 's correction formula (QTcF = QT/(RR0.33)) \> 450 ms (males) or \> 470 ms (females).

Primary outcomes:
measure: Time to sustained recovery of 11 COVID-19 symptoms
timeFrame: Baseline through Day 29
Secondary outcomes:
measure: Time to sustained recovery of 5 COVID-19 symptoms
timeFrame: Baseline through Day 29
measure: Time to sustained alleviation of 7 COVID-19 symptoms
timeFrame: Baseline through Day 29
measure: Time to sustained alleviation of 11 COVID-19 symptoms
timeFrame: Baseline through Day 29
measure: Viral load
timeFrame: Baseline through Day 14
measure: SARS-CoV-2 RNA
timeFrame: Baseline through Day 14
measure: Severe COVID-19 disease
timeFrame: Baseline through Day 29
measure: Hospitalization or death
timeFrame: Baseline through Day 29
measure: ICU stay
timeFrame: Baseline through Day 29
measure: Requiring supplemental oxygen
timeFrame: Baseline through Day 29
measure: Requiring mechanical ventilation/ECMO
timeFrame: Baseline through Day 29
measure: Death (all cause)
timeFrame: Baseline through Week 12
measure: WHO clinical progression scale score
timeFrame: Baseline through Day 29
measure: Time to sustained recovery of each targeted COVID-19 symptom
timeFrame: Baseline through Day 29
measure: Proportion of sustained recovery of COVID-19 symptoms
timeFrame: Baseline through Day 29
measure: Severity of COVID-19 symptoms
timeFrame: Baseline through Day 29
measure: Composite symptom score
timeFrame: Baseline through Day 29
measure: Treatment-Related Adverse Events (TEAEs)
timeFrame: Baseline through Day 29
measure: Serious Adverse Events (SAEs)
timeFrame: Baseline through Week 12
measure: The plasma concentration of SIM0417
timeFrame: Baseline through Day 5
Other outcomes:
measure: Time to cessation of SARS-CoV-2 viral shedding (Viral load assessment)
timeFrame: Baseline through Day 29
measure: Hospital and ICU stay
timeFrame: Baseline through Week 12
measure: COVID-19 related medical visits
timeFrame: Baseline through Day 29
measure: WHO clinical progression scale
timeFrame: Baseline through Day 29
measure: Resolution of fever
timeFrame: Baseline through Day 29
measure: Global Impression Questions
timeFrame: Baseline through Day 29
measure: Health Economic Outcome
timeFrame: Baseline through week 12
measure: viral variants
timeFrame: Baseline through Day 29
measure: drug-resistance mutation
timeFrame: Baseline through Day 29
Locations:
city: Hefei
country: China
facility: Hefei First People's Hospital
state: Anhui
city: Beijing
country: China
facility: Beijing Ditan Hospital Captial Medical University
state: Beijing
city: Chongqing
country: China
facility: Chongqing Public Health Medical Center
state: Chongqing
city: Xiamen
country: China
facility: The First Affiliated Hospital of Xiamen University
state: Fujian
city: Guangzhou
country: China
facility: Guangzhou Eighth People's Hospital Guangzhou Medical University
state: Guangdong
city: Maoming
country: China
facility: Maoming People's Hospital
state: Guangdong
city: Qingyuan
country: China
facility: Qingyuan People's Hospital
state: Guangdong
city: Shenzhen
country: China
facility: The Third People's Hospital of Shenzhen
state: Guangdong
city: Zhanjiang
country: China
facility: Central People's Hospital of Zhanjiang
state: Guangdong
city: Zhuhai
country: China
facility: The Fifth Affiliated Hospital Sun Yat-Sen University
state: Guangdong
city: Guiyang
country: China
facility: GuiZhou Province People's Hospital
state: Guizhou
city: Haikou
country: China
facility: Haikou people's Hospital
state: Hainan
city: Sanya
country: China
facility: Hainan Third People's Hospital
state: Hainan
city: Mudanjiang
country: China
facility: Mudanjiang Kangan Hospital
state: Heilongjiang
city: Wuhan
country: China
facility: Wuhan Jinyintan Hospital
state: Hubei
city: Changsha
country: China
facility: The First Hospital of Changsha
state: Hunan
city: Nanjing
country: China
facility: The Second Hospital of Nanjing
state: Jiangsu
city: Nanjing
country: China
facility: ZhongDa Hospital SouthEast University
state: Jiangsu
city: Suzhou
country: China
facility: The Fifth People's Hospital of Suzhou
state: Jiangsu
city: Taizhou
country: China
facility: Taizhou People's Hospital
state: Jiangsu
city: Wuxi
country: China
facility: Wuxi No.5 People's Hospital
state: Jiangsu
city: Xuzhou
country: China
facility: Xuzhou Infectious Disease Hospital
state: Jiangsu
city: Yangzhou
country: China
facility: Subei People's Hospital of Jiangsu province
state: Jiangsu
city: Zhenjiang
country: China
facility: The Third People's Hospital of Zhenjiang
state: Jiangsu
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University
state: Jiangxi
city: Shenyang
country: China
facility: The Sixth People's Hospital of ShenYang
state: Liaoning
city: Jinan
country: China
facility: Shandong Public Health Clinical Center
state: Shandong
city: Shanghai
country: China
facility: Shanghai Public Health Clinical Center
state: Shanghai
city: Chengdu
country: China
facility: Public health clinical center of Chengdu
state: Sichuan
city: Suining
country: China
facility: Suining Central Hospital
state: Sichuan
city: Tianjin
country: China
facility: Tianjin first center hospital
state: Tianjin
city: Hangzhou
country: China
facility: Affliated Hangzhou XiXi Hospital Zhejiang University School of Medicine
state: Zhejiang
city: Huzhou
country: China
facility: Huzhou Central Hospital
state: Zhejiang
city: Ningbo
country: China
facility: HwaMei Hospital University of Chinese Academy of Sciences
state: Zhejiang
city: Wenzhou
country: China
facility: Wenzhou Central Hospital
state: Zhejiang
Study officials:
affiliation: China-Japan Friendship Hospital
name: Chen Wang
role: PRINCIPAL_INVESTIGATOR
References: