A Phase IIa, Adaptive, Double-Blind, Randomized, Placebo-Controlled, Multi-Center Study in Hospitalized Patients Infected with Severe and Critical SARS-CoV-2 to Assess the Safety, Pharmacokinetics, Pharmacodynamics and Efficacy of MRG-001
试验速览
- 阶段
- 2 期
- 状态
- Other
- 发起方
- Medregen LLC
- 入组人数
- 40
- 试验地点
- 3
- 主要终点
- To evaluate the safety of MRG-001 in Severe and Critical SARS CoV-2 patients
研究概览
简要总结
This study is a randomized, placebo controlled, Phase IIa study in male and female subjects with severe and critical COVID-19. Hospitalized subjects with severe and critical SARS-CoV-2 infection (defined as WHO clinical improvement Scale 5 – 7) will be enrolled into the study.The study follows an adaptive design. It will be conducted in 2 stages.Both, Stage I and Stage II will be a double blinded study.Stage I: 40 subjects will be randomized into MRG-001 and placebo treatment arms at the ratio of 1:1. The attempt will be made to recruit near equal proportion of subjects across the different countries, however, considering the unpredictable nature of COVID-19 pandemic, the actual proportions may vary.The study will consist of a Screening Assessment (Day -7 to 1), a Treatment Period (Day 1 to 13 – alternate days), Follow-Up visits on Days 14, 15, 28 and End-of-Study (EOS) (Telephonic interview if discharged) at Day 60, unless improvement allows for discharge from hospital without oxygen support.
A dose level of 0.0067 mL/kg body weight of MRG-001 will be planned for subjects. (Plerixafor: 0.16 mg/kg and Tacrolimus: 0.0033mg/kg). All the subjects enrolled will receive standard treatment as per the respective national regulations along with IMP.Subjects will receive doses of MRG-001 or placebo on Days 1, 3, 5, 7, 9, 11 and 13 unless improvement allows for discharge from hospital off oxygen. Follow-up PK, PD and safety assessments will be scheduled on Days 14 and 15 and safety assessments will be conducted on Days 14, 28 and day 60 or at day of discharge, whichever follows first.Pharmacokinetic and Pharmacodynamic assessments will be performed for 20 subjects randomized to MRG-001 treatment groupand 20 subjects in placebo group. If the subjects are discharged earlier, the follow up, PK, PD and safety assessments will be performed on the day of discharge. If they complete the full course of treatment and they remain in the hospital, the follow up days would include days 14, 15, 28 and day 60. However, if they get discharged prior to day 14, only telephonic assessment is needed on days 14, 28and day 60 but not on day 15.The estimated duration of study participation (Screening through EOS Visit) for an individual subject will be approximately two months
Stage 2: This stage of the trial will be conducted based on Stage Iefficacy analysis results.Decisions on the sample size estimation, determination of efficacy end points will be based on the Stage I efficacy analysis results.
研究设计
- 研究类型
- Interventional
- 分配方式
- Permuted block randomization, fixed
- 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
- •1 Subject voluntarily agrees to participate in this study and is able to provide written informed consent or has a legal representative who can provide informed consent or is enrolled under International Conference on Harmonization (ICH) E6 (R2) 4.8.15 emergency use provisions as deemed necessary by the investigator (where permitted according to local law and approved nationally and by the relevant IRB) prior to performing any of the Screening Visit procedures.
- •2 Males and females over 18 years of age, inclusive, at the time of signing the ICF.
- •3 Hospitalized, with COVID-19 symptoms of respiratory illness caused by SARS-CoV-2 infection (defined as Scale 5 – 7 on the WHO 8-point ordinal scale for clinical improvement.
- •4 Laboratory confirmation SARS-CoV-2 by real time polymerase chain reaction in the respiratory tract (NP swab, oropharyngeal swab, tracheal aspirate, BAL) lesser or equal to 14 days prior to randomization.
- •5 Radiologic findings compatible with diagnosis of SARS-CoV-2 pulmonary infection 6 Women of childbearing potential must be willing and able to use at least one highly effective contraceptive method for a period from the screening visit until the end of study visit.
- •In the context of this study, an effective method is defined as those which result in low failure rate (i.e. less than 1 percent per year) when used consistently and correctly such as: -Combined (estrogen and progestogen containing) hormonal contraception combined (estrogen and progestogen containing) hormonal contraception (oral, intravaginal, or transdermal) -Progestogen only hormonal contraception associated with inhibition of Ovulation (oral, injectable, implantable) -Intrauterine device (IUD) -Intrauterine hormone releasing system -Vasectomized partner -Bilateral tubal occlusion -True abstinence.
- •When this is in line with the preferred and usual lifestyle of the subject.
- •Periodic abstinence, such as calendar, ovulation, symptothermal, post ovulation methods, and withdrawal are not acceptable methods of contraception.
- •7 Men must be willing to use a double barrier contraception from enrollment until at 5 months after the last dose of study drug, if not abstinent.
排除标准
- •1 Participation in any other clinical trial of an experimental treatment for COVID-19 (remdesivir use is permitted).
- •2 Significant pre existing organ dysfunction prior to randomization -Lung: Receiving supplemental home oxygen therapy at baseline for pre-existing medical condition (other than COVID-19), as documented in medical record.
- •Heart: Pre-existing congestive heart failure defined as an ejection fraction <20% as documented in the medical record.
- •clinically significant ventricular arrhythmias (ventricular tachycardia, ventricular fibrillation), unstable angina, myocardial infarction (past 3 months), heart and coronary vessel surgery (past 3 months), significant valvular heart disease, uncontrolled arterial hypertension with systolic blood pressure >180 mm Hg and diastolic blood pressure >110 mm Hg. -Renal: End-stage renal disease requiring renal replacement therapy or eGFR <30 mL/min -Liver: Severe chronic liver disease defined as Child Pugh Class C -Hematologic: Baseline platelet count <50,000/mm3 3 Concurrent treatment or prior use of drugs with actual or possible direct acting immunomodulatory activity against ARDS in COVID-19 is prohibited including JAK1/JAK2 inhibitor ruxolitinib, baricitinib and tofacitinib.
- •However, IL-6 inhibitors such as tocilizumab, sarilumab are allowed if given >72 hours prior to first study dose.
- •Corticosteroids are permitted throughout the study.
- •4 History of splenectomy or splenomegaly (spleen weighing >750 g) 5 Body mass index of >45 kg/m2 at screening 6 Underlying malignancy, or other condition, with estimated life expectancy of less than two months 7 Known family history of long QT syndrome (Torsades de Pointes) or currently taking medication that prolongs QT interval 8 Currently taking immunomodulating biologics (e.g., interferons, interleukin).
- •9 Extracorporeal membrane oxygenation (ECMO) 10 Use of two or more vasopressors 11 Female subjects who are pregnant or breastfeeding or planning to breastfeed at any time through 90 days after last dose of IP.
- •12 Received a live attenuated vaccine within 30 days prior to enrollment.
- •13 Positive test for Hepatitis B surface antigen (HBsAg), Hepatitis C antibody, human immunodeficiency virus (HIV) antibody or Active tuberculosis or a history of inadequately treated tuberculosis.
- •14 Ongoing immunosuppression: solid organ transplant recipients 15 Has used an investigational drug within 30 days prior to Screening.
- •16 History of hypersensitivity to MRG-001 (plerixafor [AMD3100, 24 mg/mL]) and tacrolimus [FK506, 0.5 mg/mL]) or any of the excipients or to medicinal products with similar chemical structure 17 Current treatment with an anti-viral medication for COVID-19 (e.g. hydroxychloroquine, lopinavir/ritonavir), other than remdesivir 18 Unable to understand the protocol requirements, instructions and study related restrictions, the nature, scope and possible consequences of the clinical study 19 Unlikely to comply with the protocol requirements, instructions and study related restrictions, e.g., uncooperative attitude, inability to return for follow-up visits and improbability of completing the clinical study.
- •21 Vulnerable subjects defined as individuals whose willingness to volunteer in a clinical study may be unduly influenced by the expectation, whether justified or not, of benefits associated with participation, or of a retaliatory response from senior members of a hierarchy in case of refusal to participate (e.g., persons in detention, minors and those incapable of giving consent) 22 Any condition that in the opinion of the treating physician will increase the risk for the participant.
结局指标
主要结局
To evaluate the safety of MRG-001 in Severe and Critical SARS CoV-2 patients
时间窗: From Baseline to Day 60 or discharge
次要结局
- -To evaluate the efficacy of MRG-001 in Severe and Critical(SARS-CoV-2 patients.)