Efficacy and Safety of SR1375 in Adult Patients With CAP

Официальное название

A Randomized, Double-blind, Placebo-controlled Phase II Study to Evaluate the Efficacy and Safety of SR1375 in Hospitalized Adult Patients With Community-acquired Pneumonia

Обзор

This is a phase 2 study to evaluate the efficacy and safety of SR1375 in hospitalized adult patients with CAP. Patients will receive SR1375 or placebo for 8 weeks. The study duration for each patient is up to 10 weeks.

Подробное описание

This is a randomized, double-blind and placebo-controlled phase 2 study comparing SR1375 with placebo in adult patients with CAP. It consists of a screening period, a double-blind treatment period, and a post-treatment safety follow-up period. Baseline NIAID-OS 8-point scale score will be checked for eligibility. Around 240 eligible subjects will be recruited and randomized into four arms at 1:1:1:1 ratio to receive SR1375 0.3mg, SR1375 1mg, SR1375 3mg or placebo orally daily for 56 days. Subjects, investigators, all clinical study site staffs, and the Sponsor will remain blinded to treatment assignment during the study. Subjects will receive regular treatments as per his/her condition by investigator. After completion of double-blind treatment period, subjects will continue to complete the safety follow-up for 14 days.

Вмешательства

• Препарат SR1375 capsule 3mg+regular treatments
  SR1375 capsule 3mg QD orally+CAP regular treatments
• Препарат SR1375 capsule 1mg+regular treatments
  SR1375 capsule 1mg QD orally+CAP regular treatments
• Препарат SR1375 capsule 0.3mg+regular treatments
  SR1375 capsule 0.3mg QD orally+CAP regular treatments
• Препарат Placebo capsule+regular treatments
  Placebo capsule QD orally+CAP regular treatments

Первичные конечные точки

• National Institute of Allergy and Infectious Diseases-Outcome Study (NIAID-OS) 8-point scale score [Срок оценки: Up to Day 28]

Вторичные конечные точки (12)

• Proportion of subjects ≥ 2 points improvement in National Institute of Allergy and Infectious Diseases-Outcome Study (NIAID-OS) 8-point scale score [Срок оценки: Up to Day 28]
• National Institute of Allergy and Infectious Diseases-Outcome Study (NIAID-OS) 8-point scale score [Срок оценки: Up to Day 14]
• All-cause mortality rate [Срок оценки: Up to Day 56]
• Proportion of subjects with invasive mechanical ventilation, Extracorporeal Membrane Oxygenation(ECMO) or all-cause death. [Срок оценки: Up to Day 56]
• Partial Pressure of Oxygen(PaO2)/Fraction of Inspiration Oxygen(FiO2) [Срок оценки: Up to Day 28]
• Proportion of subjects admitted in ICU or all-cause death [Срок оценки: Up to Day 56]
• Proportion of subjects ≤ 2 points in NIAID-OS 8-point scale [Срок оценки: Up to Day 56]
• Survival days without invasive mechanical ventilation or ECMO [Срок оценки: Up to Day 56]
• Survival days without ICU admission [Срок оценки: Up to Day 56]
• Days of hospitalization [Срок оценки: Up to Day 56]
• All-cause readmission rate [Срок оценки: Up to Day 56]
• Readmission rate due to pneumonia [Срок оценки: Up to Day 56]

Критерии участия

Критерии включения

• The subject or their legally acceptable representative (LAR) has voluntarily signed the informed consent form (ICF) prior to any study-related procedures, and the subject is willing and able to comply with all study requirements, restrictions, and procedures. If consent is provided by an LAR for a subject with limited or no capacity to consent, re-consenting may be performed if the subject regains capacity.
• Aged 18 to 85 years.
• Diagnosis of CAP
• Prior to screening, the subject has been receiving standard-of-care treatment for pneumonia in a medical institution, including at least 3 days of intravenous (IV) anti-infective therapy, with no clinical improvement.
• Chest CT showing multi-lobar infiltrates, and for subjects not receiving invasive mechanical ventilation, an oxygenation index (PaO2/FiO2 ratio) between 100 and 300 mmHg.
• Expected to require continued hospitalization for at least 7 days from the time of signing the ICF.
• Baseline NIAID-OS 8-point scale score of 5 points and transcutaneous oxygen saturation ≤ 93% without oxygen inhalation, 6 points or 7points. (5 points refer to hospitalization with oxygen therapy; 6 points refer to hospitalization with high flow oxygen therapy or non-invasive mechanical ventilation. 7 points refer to hospitalization with invasive mechanical ventilation).High oxygen flow refers to ≥ 4 L/min.)
• With ≥ 1 high risk factors including chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, type 2 diabetes, chronic kidney disease, coronary heart disease, age ≥ 65 years, moderate obesity (body mass index>32.5kg/m2), etc.
• Participants of women of childbearing potential(WOCBP) and male participants with WOCBP partners must agree to use one or more effective contraceptive methods during the treatment period and until 90 days after the last administration.

Критерии исключения

• Patients who are currently receiving or are expected to require ECMO treatment within 24 hours.
• Presence of active tuberculosis (TB) or severe asthma.
• History of unstable angina or acute myocardial infarction within 3 months prior to screening, or stroke within 4 weeks prior to screening.
• Received chemotherapy and/or immunotherapy for a malignant tumor within 4 weeks prior to randomization, or are planned to receive such treatment during the study period; presence of a hematological malignancy not in complete remission; or a lung tumor with concurrent obstructive pneumonia.
• Presence of any concomitant disease that is expected to result in death within 12 weeks after randomization.
• Prior use of JAK inhibitors (e.g., Baricitinib), interleukin receptor inhibitors (e.g., Tocilizumab), or any investigational drug in another clinical trial, where the last dose was administered less than 5 half-lives before the first dose of the study drug in this trial.
• ALT) or AST > 3 times the upper limit of normal (ULN).
• eGFR < 30 mL/min/1.73 m² (calculated using the Chronic Kidney Disease Epidemiology Collaboration \[CKD-EPI\] formula); however, patients undergoing dialysis may be included upon the investigator's assessment of their suitability for the trial.
• Presence of clinically significant abnormalities on ECG that may seriously affect subject safety, e.g., QTcF > 480 ms.
• Female subjects who are pregnant, lactating, or have a positive serum β-HCG pregnancy test.
• Presence of any severe systemic disease or clinical condition that, in the investigator's judgment, makes the subject unsuitable for participation in this study.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Китай · 29 центров

• Fuyang People's Hospital — Fuyang
• Peking University Third Hospital — Пекин
• Zhangzhou Hospital — Zhangzhou
• Gaozhou People's Hospital — Gaozhou
• The First Affiliated Hospital of Sun Yat-sen University — Гуанчжоу
• The Third Affiliated Hospital of Southern Medical University — Гуанчжоу
• Nanfang Hospital — Гуанчжоу
• The First Affiliated Hospital of Shantou University Medical College — Shantou
• … и ещё 21 центр

Идентификаторы

NCT: NCT06577558 · SR1375-204

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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