RESPIRE - A Randomized, Double-Blind, Placebo-Controlled, Multi-Centre Clinical Trial to Evaluate the Safety and Efficacy of ATR-002 in Adult Hospitalized Patients with COVID-19
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 220
- 试验地点
- 7
- 主要终点
- Clinical severity status on a 7 point ordinal scale at Day 15
研究概览
简要总结
This is a Phase 2, multi-center, randomized, double-blind, controlled, parallel group, two-arm clinical trial (ATR-002 vs. placebo). The study will assess the efficacy and safety of ATR-002 versus a matching placebo, as well as pharmacokinetics of ATR-002 in adult hospitalized patients with COVID-19. Study participants will additionally receive throughout the clinical trial any treatment that is considered standard of care as per local standards. To minimize bias, the clinical trial will be randomized and double-blind. Following screening procedures, eligible study participants will be centrally assigned to randomized investigational medicinal product (IMP) using Interactive Response Technology (IRT). The control group will receive matching placebo to the treatment (ATR-002) group. Drug concentration information will not be reported to study sites or blinded study personnel until the clinical trial has been unblinded. An independent Data Monitoring Committee will convene in accordance with clinical trial progress, i.e. after 20 study participants have been treated and then again after each 50 study participants have been treated. In addition, special meetings can take place if concerns about the safety of study participants arise. The clinical trial comprises a screening period of up to approximately 24 hours (on Day –1), followed by a 6-day treatment period on Days 1 to 6, and follow-up at defined time points up to Day 90.
Study participants will receive IMP (ATR-002 or placebo) orally once daily for 6 days. The daily dose of ATR-002 will be 900 mg on Day 1 and 600 mg on Days 2 to 6.
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Participant and Investigator Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 99.00 Year(s)（—）
- 性别
- All
入选标准
- •Informed Consent
- •Capable of giving signed informed consent as described in Section 10.1.3, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
- •Study participant must be at least 18 years of age at the time of signing the ICF.
- •Type of Participant and Disease Characteristics 3.1 Study participants in India with a laboratory confirmed diagnosis of SARS-CoV-2 infection presenting as moderate COVID-19 requiring hospitalization for COVID-19 and for medical reasons (see Section 8 and CLINICAL MANAGEMENT PROTOCOL: COVID-19, Government of India, Version 5, 03.07.20).
- •3.2 At least one of the following clinical features need to be present: Dyspnea Hypoxia Fever Cough AND 3.3 SpO2 between 90% and 93% on room air AND 3.4 Respiratory Rate more or equal to 24 and less than 30 breaths per minute Patients presenting to the hospital without a laboratory confirmed SARS-CoV-2 infection will be tested locally for SARS-CoV-2 during the screening period.
- •For sites in the EU: A CE certified SARS-CoV-2 PCR test kit is required to confirm infection.
- •For sites outside the EU: SARS-CoV-2 PCR test kits certified according to local regulations are required to confirm infection.
- •Male or female.
- •Pregnancy and Contraception Contraceptive use by women and men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
- •A female study participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies: a.
- •She is not a WOCBP as defined in Section 10.3.
- •Is a WOCBP and is using a contraceptive method that is highly effective, with a failure rate of <1%, as described in Section 10.3.2 during the IMP period and for at least 4 weeks after the last dose of IMP.
- •The investigator should evaluate the potential for contraceptive method failure (e.g., noncompliance, recently initiated) in relationship to the first dose of IMP.
- •A WOCBP must have a negative urine pregnancy test within 24 hours before the first dose of IMP, see Section 8.3.
- •If a urine pregnancy test cannot be confirmed as negative (e.g., an ambiguous result), a serum pregnancy test is required locally.
- •In such cases, the participant must not be randomized if the serum pregnancy result is positive.
- •If a serum pregnancy test is required as per local regulations, a serum pregnancy test is required locally.
- •A male study participant is eligible to participate if: a.
- •He is azoospermic b.
- •The partner is not a WOCBP as defined in Section 10.3.
- •The partner is a WOCBP and is using a contraceptive method that is highly effective, with a failure rate of <1%, as described in Section 10.3.2 during the IMP period and for at least 90 days after the last dose of IMP.
- •He acknowledges that sperm donation is prohibited from the first dose of IMP until at least 90 days after the last dose of IMP.
排除标准
- •Patient’s clinical condition is worsening rapidly.
- •Requiring ICU admission or ventilator support at screening or at randomization.
- •Suspected bacterial, fungal, viral, or other infection (besides COVID-19).
- •History of any of the following: malignant disease, autoimmune disease, or severe liver, kidney, blood, cardiac, pulmonary, neurological, or endocrine disease as judged by the investigator.
- •The medical monitor should be contacted by the investigator.
- •5.1 Patients with uncontrolled hypertension (BP ≥ 140/90 mmHg).
- •Clinically significant cardiac conduction abnormalities, including QTc prolongation of > 450 milliseconds.
- •Family history of Long QT Syndrome.
- •Heart failure class 3, or 4, as defined by the New York Heart Association (NYHA).
- •9.1 History of acute coronary syndrome (including myocardial infarction), coronary angioplasty, stenting, or thromboembolic event within 24 weeks prior to screening.
- •Patients with implanted defibrillators or permanent pacemakers.
- •Poorly controlled diabetes mellitus with an HbA1c > 7.5 %.
- •Renal disease including glomerulonephritis, nephritic syndrome, Fanconi Syndrome, or renal tubular acidosis.
- •Renal failure requiring renal replacement therapy or moderate renal impairment as defined by having an estimated glomerular filtration rate (eGFR, CKD-EPI) < 45 ml/min/1.73m
- •Chronic Obstructive Pulmonary Disease (COPD) GOLD C, or D, or hospitalization for exacerbation of COPD within 24 weeks prior to screening.
- •Other chronic lung diseases including cystic fibrosis, neuromuscular diseases, severe chest wall deformities, interstitial lung diseases, outpatient chronic non-invasive ventilation due to chronic respiratory failure.
- •Asthma with a symptom control level of "uncontrolled", according to current GINA guidelines.
- •Currently suffering from diseases that seriously affect the immune system, such as: human immunodeficiency virus (HIV) infection, or the blood system, or splenectomy, or organ/ stem cell transplantation.
- •Known Hepatitis B or C infection.
- •Any medical condition, physical examination finding or laboratory abnormality that, in the opinion of the investigator, might confound the results of the study or pose an additional risk to the patient.
- •Alanine transaminase (ALT) or aspartate transaminase (AST) >3.0 x ULN.
- •Prior/Concomitant Therapy
- •Taking concomitant medication metabolized by CYP2C8 and/ or CYP2C9 and listed as “prohibited†in Section 10.
- •Any such treatments must be washed out for 30 days or at least 5 half-lives prior to randomization, whichever is longer, unless a formal written standard of care policy document requires otherwise.
- •Inclusion needs to be approved by the investigator and medical monitor.
- •Taking medication that may seriously affect the immune system, e.g., chemotherapy, unless considered and documented as standard of care (e.g., corticosteroids) to treat COVID-
- •Prior/Concurrent Clinical Study Experience
- •Currently participating in other clinical trials or previous treatment with an investigational medicinal product within 5 half-lives or 30 days (whichever is longer) prior to randomization.
- •Other Exclusions
- •Known allergy or hypersensitivity to the IMP (including excipients).
- •Study participant is pregnant or breastfeeding.
- •Patient has been committed to an institution by virtue of an order issued either by the judicial or the administrative authorities.
结局指标
主要结局
Clinical severity status on a 7 point ordinal scale at Day 15
时间窗: Day 15
Time from randomization to discharge from hospital
时间窗: Day 15
Time to resolution of fever defined as ≤36.6°C (axilla) ≤37.2°C (oral) or ≤37.8°C (rectal or tympanic) for at least 24 hours without antipyretics for 24 hours.
时间窗: Day 15
Time to discharge from hospital or to score of ≤2 maintained for 24 hours in NEWS2 whichever occurs first
时间窗: Day 15
Time to SpO2 94% on room air maintained for 24 hours
时间窗: Day 15
次要结局
- Clinical severity status on a 7 point ordinal scale at Day 15(Time from randomization to discharge from hospital)