CTRI/2021/12/038577进行中（未招募）2 期
A phase 2 Randomized, Double-blind, Placebo-controlled Trial and Open-Label Extension to Evaluate Safety and Efficacy of Deupirfenidone (LYT-100) in Post-acute COVID-19 Respiratory Disease.
适应症
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- PureTech
- 入组人数
- 168
- 试验地点
- 6
- 主要终点
- To evaluate the effect of LYT-100 on the change in distance walked on six-minute walk test (6MWT) performed as per the American Thoracic Society/European Respiratory Society Guidelines (Crapo et al 2002).
研究概览
简要总结
This is a Phase 2 Randomized, Double-blind, Placebo-controlled Trial and Open Label Extension to Evaluate the Safety and Efficacy of Deupirfenidone (LYT-100) in Post-acute COVID-19 Respiratory Disease.
This study will be conducted in two parts, A and B. Part A is a phase 2 multi-centre randomized, double-blind, parallel arm, placebo-controlled study being conducted to evaluate the safety and efficacy of Study drug (LYT-100) compared to placebo in post-acute adult patients with COVID-19 respiratory disease who were treated with supplemental oxygen (including MV, ECMO or any other means of oxygen administration) in the hospital for at least 1 day and have required only low flow nasal oxygen or no oxygen supplementation for at least 72 hours prior to screening. The second part of the study, Part B, is an open-label extension (OLE) in which eligible patients who completed Part A will be enrolled and treated with open-label study drug (LYT-100) for an additional 91 days.
The study will be performed in approximately 35 clinical sites in Europe, the US, Asia, South America, UK and LATAM.
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 80.00 Year(s)（—）
- 性别
- All
入选标准
- •Inclusion Criteria-Part A:
- •Positive result of a molecular RT-qPCR diagnostic test or SARS-CoV-2 RNA result from a clinical specimen deemed clinically associated with the current episode of illness, warranting hospital admission as per investigator’s judgement, or previously hospitalized (central and/or local laboratory COVID-19 test results are accepted from any biological material source)
- •Hospitalization for COVID -19 respiratory disease and treated with supplemental oxygen (including MV, ECMO or any other means of oxygen administration) in hospital for at least 1 day
- •Male or female, aged ≥18 to ≤80 years of age, inclusively at the time of informed consent
- •Able to perform and willing to comply with all study procedures and requirements
- •Able to bear weight and ambulate a minimum of 10 m distance (use of inhaled oxygen permitted)
- •Randomization day is dependent on type of qualifying respiratory support and date of initial confirmed COVID-19 diagnosis as described in Table 1
- •COVID-19 pneumonia findings on imaging (chest X-ray or CT Scan) with a minimum of two lung lobes involvement
- •Shortness of breath ≥ grade 3 on mBDS dyspnea scale
- •Laboratory parameters (CBC, biochemistry) deemed by the investigator as acceptable and/or not clinically significant to enroll the patient
- •Women of childbearing potential (WOCBP) must be non-pregnant and non-lactating, and must be abstinent from heterosexual intercourse for 90 days following last dose of study medication or agree to use one of the acceptable, highly effective double contraception: a.
- •oral, intravaginal, or transdermal combined (estrogen and progesterone containing) hormonal contraception associated with inhibition of ovulation b.
- •oral, injectable, or implantable progestogen-only hormonal contraception associated with inhibition of ovulation c.
- •intrauterine device (IUD)
- •Male patients must be surgically sterile (> 30 days since vasectomy with no viable sperm), abstinent, or if engaged in sexual relations with a WOCBP, the participant and his partner must be surgically sterile (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy, bilateral oophorectomy) or using an acceptable, highly effective contraceptive method from screening until study completion, including the follow-up period and an additional 90 days after the last dose of study medication
- •Males will not donate sperm for at least 90 days after the last dose of study medication
- •Partners of male patients and female patients will report pregnancy occurring within 90 days from cessation of study medication
- •Patients can be on other medication (on and off label), apart from the ones specifically outlined in the Exclusion Criteria to treat COVID-19 respiratory disease that the investigator deems clinically relevant in combination with the study drug
- •Patients can concomitantly receive any standard of care as per investigators’ clinical decision; standard of care may encompass any approved medication, on or off label apart from the ones specifically outlined in the exclusion criteria.
- •Concomitant medication may be other medication(s) apart from the ones specifically outlined in the Exclusion Criteria.
- •Inclusion Criteria-Part B:
- •Patient must have completed Part A of the study, through Day 91 of treatment.
- •In the opinion of the Investigator, the patient is a good candidate for continued treatment.
排除标准
- •Inclusion Criteria-Part A:
- •Positive result of a molecular RT-qPCR diagnostic test or SARS-CoV-2 RNA result from a clinical specimen deemed clinically associated with the current episode of illness, warranting hospital admission as per investigator’s judgement, or previously hospitalized (central and/or local laboratory COVID-19 test results are accepted from any biological material source)
- •Hospitalization for COVID -19 respiratory disease and treated with supplemental oxygen (including MV, ECMO or any other means of oxygen administration) in hospital for at least 1 day
- •Male or female, aged ≥18 to ≤80 years of age, inclusively at the time of informed consent
- •Able to perform and willing to comply with all study procedures and requirements
- •Able to bear weight and ambulate a minimum of 10 m distance (use of inhaled oxygen permitted)
- •Randomization day is dependent on type of qualifying respiratory support and date of initial confirmed COVID-19 diagnosis as described in Table 1
- •COVID-19 pneumonia findings on imaging (chest X-ray or CT Scan) with a minimum of two lung lobes involvement
- •Shortness of breath ≥ grade 3 on mBDS dyspnea scale
- •Laboratory parameters (CBC, biochemistry) deemed by the investigator as acceptable and/or not clinically significant to enroll the patient
- •Women of childbearing potential (WOCBP) must be non-pregnant and non-lactating, and must be abstinent from heterosexual intercourse for 90 days following last dose of study medication or agree to use one of the acceptable, highly effective double contraception: a.
- •oral, intravaginal, or transdermal combined (estrogen and progesterone containing) hormonal contraception associated with inhibition of ovulation b.
- •oral, injectable, or implantable progestogen-only hormonal contraception associated with inhibition of ovulation c.
- •intrauterine device (IUD)
- •Male patients must be surgically sterile (> 30 days since vasectomy with no viable sperm), abstinent, or if engaged in sexual relations with a WOCBP, the participant and his partner must be surgically sterile (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy, bilateral oophorectomy) or using an acceptable, highly effective contraceptive method from screening until study completion, including the follow-up period and an additional 90 days after the last dose of study medication
- •Males will not donate sperm for at least 90 days after the last dose of study medication
- •Partners of male patients and female patients will report pregnancy occurring within 90 days from cessation of study medication
- •Patients can be on other medication (on and off label), apart from the ones specifically outlined in the Exclusion Criteria to treat COVID-19 respiratory disease that the investigator deems clinically relevant in combination with the study drug
- •Patients can concomitantly receive any standard of care as per investigators’ clinical decision; standard of care may encompass any approved medication, on or off label apart from the ones specifically outlined in the exclusion criteria.
- •Concomitant medication may be other medication(s) apart from the ones specifically outlined in the Exclusion Criteria.
- •Inclusion Criteria-Part B:
- •Patient must have completed Part A of the study, through Day 91 of treatment.
- •In the opinion of the Investigator, the patient is a good candidate for continued treatment.
- •Exclusion Criteria-Part A:
- •Patients who cannot follow-up with study participation requirements
- •Investigator considers patient is inappropriate to enroll in the trial
- •Patients with history of Idiopathic Pulmonary Fibrosis (IPF), lung cancer, pulmonary arterial hypertension, other interstitial lung diseases, severe cardiac insufficiency (grade IV) are excluded irrespective of whether they are actively being medicated for those conditions or not.
- •Pre-existing co-morbid conditions preventing outcome assessments, e.g., neurological, medical, orthopedic injury/disability, disease or condition that would prevent ability to transfer and walk for 6 minutes, prior to confirmed COVID-19 diagnosis
- •Co-morbid diagnosis of tuberculosis
- •Unstable angina or myocardial infarction in the last month prior to screening
- •Pre-existing co-morbidity associated with life expectancy less than 1 year
- •Present life expectancy less than 3 days and/or LDH > 360
- •Body mass index ≥ 45kg/m2
- •Resting heart rate of ≥ 120 bpm, systolic blood pressure of > 180 mm Hg and a diastolic blood pressure of > 100 mm Hg and/or or a fall in pulse oximetry oxygen saturation (SpO2) to <80% upon ambulation
- •Patients on MV, ECMO, NIV, HFNO or other high flow oxygen (FiO2 ≥35% and flow rate ≥ 8 lpm) within the last 72 hours prior to screening
- •History of anaphylactic reaction (particularly reactions to general anesthetic agents); allergic reaction due to any drug which led to significant morbidity; prior allergic reaction to pirfenidone.
- •Known symptoms of dysphagia or known difficulty in swallowing capsules and/or total gastrectomy
- •Patients undergoing dialysis or hemoperfusion, or with a history of dialysis or hemoperfusion, or anticipated to require dialysis or hemoperfusion within 72 hours of screening or severe renal impairment (defined as creatinine clearance rate <30 mL/min) at the time of screening/baseline.
- •Use of any of the following drugs: a.
- •Treatment with steroids under institutional protocols and guidelines to manage COVID-19 pneumonia/respiratory symptoms is allowed.
- •Use of steroids off-label to treat non-COVID-19 related conditions is not allowed.
- •â€¢ Inhaled corticosteroids are allowed.
- •â€¢ Patients that received prior convalescent plasma are allowed; however, concomitant convalescent plasma is excluded.
- •Excluded agents • Patients on concomitant experimental anti-viral, anti-fibrotic or anti-inflammatory therapies are excluded.
- •â€¢ Any investigational agent not explicitly on this list should be reviewed by the medical monitor prior to initiating therapy or enrolling participant.
- •Other inhibitors of CYP1A2 (including but not limited to methoxsalen or mexiletine) e.
- •Inducers of CYP1A2 (such as phenytoin), CYP2C9 or 2C19 (including but not limited to carbamazepine or rifampin) f.
- •Drugs associated with substantial risk for prolongation of the QTc interval (including but not limited to moxifloxacin, quinidine, procainamide, amiodarone, sotalol).
- •Note that QTc prolongation is not an all / nothing drug effect, and specifically the administration drugs such as hydroxychloroquine do not preclude participation in this trial but does mandate measurement of the QTc every 6 hours until deemed necessary in accordance with investigator judgement g.
- •Vaccination with a live vaccine is not permitted during the period from 4 weeks prior to screening to 4 weeks after the last dose h.
- 另有 7 项未显示
结局指标
主要结局
To evaluate the effect of LYT-100 on the change in distance walked on six-minute walk test (6MWT) performed as per the American Thoracic Society/European Respiratory Society Guidelines (Crapo et al 2002).
时间窗: All patients will be treated up to 91 consecutive days during the study treatment period. Study assessments are at Days 14, 28, 56 and Day 91 ± 3 days.
次要结局
- To assess the longer-term safety, tolerability, and efficacy of LYT-100 through up to 182 days of treatment(Patients who complete 91 days of treatment in Part A and who are eligible may elect to participate in Part B. All patients will be treated in Part B up to 91 consecutive days, with study assessments on Days 91, 105, 119, 147 and 182.)
研究者
研究点 (6)
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