Double-blind, Randomized, Placebo-controlled, Pilot Clinical Trial to Evaluate the Safety, Tolerability and Efficacy of Two Doses of a Conditioned Medium From a Co-culture of M2-macrophages and Fat-derived Mesenchymal Cells (PRS CK STORM) in the Modulation of the Cytokine Storm in Patients With Acute Respiratory Infection Caused by SARS-Cov-2, Influenza A, Influenza B and Respiratory Syncytial Virus (RSV)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 50
- 试验地点
- 4
- 主要终点
- Adverse Events (AEs)
研究概览
简要总结
The purpose of this clinical trial is to evaluate the safety, tolerability and efficacy of two doses (dose A and dose B) of Standardized Conditioned Medium Obtained by Coculture of M2-macrophages and fat-derived Mesenchymal Stromal Cells (PRS CK STORM) in the modulation of the cytokine storm in participants with acute respiratory infection caused by SARS-Cov-2, influenza A, influenza B and respiratory syncytial virus (RSV) in need for oxygen therapy.
The main questions it aims to answer are:
- Are both doses of PRS CK STORM (dose A and dose B) safe as an intravenous drug to modulate inflammatory processes, such as the cytokine storm in participants with SIRS caused by SARS-Cov-2, influenza A, influenza B and RSV?
- Are both doses of PRS CK STORM (dose A and dose B) effective as an intravenous drug to modulate SIRS-associated cytokine storm caused by SARS-Cov-2, influenza A, influenza B and RSV compared to the control group?
- What are the anti-inflammatory and pro-inflammatory cytokine profiles after treatment with two different doses of PRS CK STORM in participants with SIRS caused by SARS-Cov-2, influenza A, influenza B and RSV?
Researchers will compare both doses of PRS CK STORM with the control group to test whether the anti-inflammatory action of PRS CK STORM is safe and effective in modulating the cytokine storm for the treatment of SIRS caused by SARS-Cov-2, influenza A, influenza B and RSV. In addition, the anti-inflammatory and pro-inflammatory cytokine profiles after treatment PRS CK STORM compared to placebo group in these participants will be also studied.
详细描述
This is a double-blind, randomized, phase I/II pilot clinical trial of two doses of PRS CK STORM in adult participants with SIRS caused by SARS-Cov-2, influenza A, influenza B and RSV All participants will receive the standard of care for SIRS, according to its viral origin:
- Clinical management of COVID-19: hospital care (Centro de Coordinación de Alertas y Emergencias Sanitarias, 2020).
- Clinical practice guidelines for influenza (WHO, 2024). Participants who meet the eligibility criteria will be randomized in blocks to reach the 2:2:1 ratio (dose A: dose B: placebo).
This study consists of two parts:
Part 1: Doses A and B of PRS CK STORM will be evaluated in 2 groups of 4 participants (3:1; PRS CK STORM: placebo). It starts with a first sentinel group of 4 participants who will be assigned to placebo or study drug dose A. First, only 2 participants will randomly be assigned to receive the active treatment of dose A or placebo for 5 consecutive days. These 2 first participants will be followed up to 48h after the last drug administration (short-term safety follow-up period) when a safety assessment will be completed before treating the other 2 participants in this group.
If the study drug is considered safe during the short-term safety assessment planned 48h after the last drug administration, then 2 additional participants will be treated with dose A for 5 consecutive days to complete the first sentinel group of 4 participants. These 2 participants will be followed up to 48h after the last study drug administration before moving to dose B.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent by the participant or legal representative prior to the initiation of any study-specific procedure.
- •Males and females aged ≥ 18 years old at the time of the consent.
- •Confirmed diagnosis of SARS-CoV-2, influenza virus A, influenza virus B or RSV pneumonia by positive RT-PCR (results of a PCR prior to screening will be valid only if the PCR has been done for all 4 viruses and in 3 days prior to the screening visit). PCR will include the analysis of SARS-Cov-2, influenza A, influenza B and RSV.
- •Diagnosis of systemic inflammatory response syndrome (SIRS), defined by the satisfaction of any two of the criteria below:
- •Body temperature over 38 ºC or under 36 ºC.
- •Heart rate greater than 90 beats/minute.
- •Respiratory rate higher than 20 breaths/min or PaCO2 lower than 32 mmHg.
- •Leukocyte count higher than 12000/μL, lower than 4000/μL or over 10% immature forms or bands.
- •Need for oxygen therapy.
- •Female participants must be, either surgically sterilized or at least 1 year postmenopausal (confirmed by follicle-stimulating hormone [FSH] more than 20 international units [Ius] only for women under 54) or using adequate birth control (hormonal contraception, intrauterine contraceptive device, double barrier methods [condom with spermicide, diaphragm with spermicide, or condom and diaphragm]) or sexual abstinence for up to 90 days after the last treatment administration. Male participants must be willing to use barrier contraception (condom) for up to 90 days after the last treatment administration.
排除标准
- •Failure to perform screening or baseline examinations.
- •Body Mass Index (BMI) more than or equal to
- •Irreversible critical condition, as assessed by the investigator.
- •Active autoimmune diseases or severe immunosuppression, unless stable and controlled for at least 3 months prior to the inclusion in the study.
- •Clinically significant, advanced or unstable disease that may interfere with primary or secondary variable evaluations, may bias the clinical assessment, such as:
- •Liver function test abnormalities or other signs of hepatic insufficiency not justified by a pulmonary acute inflammation process: Aspartate transaminase (AST), alanine transaminase (ALT) more than 3 per upper limit of the reference range, total bilirubin more than or equal to 2 mg/dL; except for subjects with isolated elevation of indirect bilirubin relating to Gilbert syndrome.
- •Renal insufficiency (serum creatinine more than 2 mg/dL (more than 150 μmol/L) and creatinine clearance less than 30 (according to Cockcroft-Gault formula).
- •Myocardial infarction, unstable angina, heart failure within 3 months before screening.
- •Bradycardia (heartbeat less than 50/min).
- •Atrioventricular block (type II / Mobitz II and type III), congenital long QT syndrome, sinus node dysfunction or prolonged QTcF interval (males more than 450 msec and females more than 470 msec using Fridericia's formula: QTc = QT/ RR^2 ).
- •Uncontrolled diabetes mellitus (blood glucose level above 500 mg/dL) at the time of admission.
- •Malignant tumors within the last 5 years, unless stable during that time. Skin malignancies (other than melanoma) and indolent prostate cancer are excluded from this criterion.
- •Metastases.
- •Human Immunodeficiency Virus (HIV), HBV [hepatitis B surface antigen (HBs Ag) positive (+), or detected sensitivity on the HBV deoxyribonucleic acid (DNA), polymerase chain reaction (PCR) qualitative test for hepatitis B core antibody (HBc Ab) positive subjects] or HCV [HCV ribonucleic acid (RNA) detectable in any subject with positive anti-HCV antibody (HCV Ab)].
- •Inability to comply with the study and monitoring procedures.
- •Pregnant and breastfeeding females (pregnancy test positive).
- •Suspected or known active drug or alcohol abuse.
- •Enrollment in another investigational drug study within 1 month before the screening
- •Subject who has any condition, including any psychological or psychiatric condition, in the opinion of the Investigator, would compromise the safety of the subject or the quality of the data and renders the subject an unsuitable candidate for the study.
研究组 & 干预措施
PRS CK STORM - dose A
A sterile secretome derived from the co-culture of M2-type macrophages and ASC (adipose stromal cells) containing 116,059 pg/mL Tissue Inhibitor of Matrix Metalloproteinase- 1 (TIMP-1). Participants will receive a total dose of 1,160,585.366 pg of TIMP-1 via IV infusion
干预措施: PRS CK STORM (Drug)
PRS CK STORM - dose B
A sterile secretome derived from the co-culture of M2-type macrophages and ASC (adipose stromal cells) containing 232,017 pg/mL TIMP-1. Participants will receive a total dose of 1,160,585.366 pg of TIMP-1 via IV infusion.
干预措施: PRS CK STORM (Drug)
Saline Solution 0,9% for injection
Participants will receive 2 vials, containing each 10 mL of Intravenous (IV) infusion of normal saline (0.9%)
干预措施: Placebo comparator (Drug)
结局指标
主要结局
Adverse Events (AEs)
时间窗: Up to 12 months
Number and proportion of subjects experiencing AEs.
Serious adverse events (SAEs)
时间窗: Up to 12 months
Number and proportion of subjects experiencing SAEs
Treatment-emergent adverse events (TEAEs)
时间窗: Up to 12 months
Number and proportion of subjects experiencing TEAEs
Safety measures: Clinical evaluation through physical examination
时间窗: Day 7, Day 30, Day 90 and Day 365
Number and proportion of subjects with abnormal findings of physical examination parameters (head, ears, Nervous system,Gastrointestinal system, Respiratory system, Lymph nodes Musculoskeletal system, Neck, Throat, Cardiovascular system, Skin, Nose) will be evaluated
Changes from Baseline in vital signs: body temperature
时间窗: From Day 1 to Day 7, Day 30, Day 90 and Day 365
Body Temperature of participants will be measure d in Celsius (ºC)
Changes from Baseline in vital signs: oximetry
时间窗: From Day 1 to Day 7, Day 30, Day 90 and Day 365
Levels of blood oxygen saturation (SpO2) using a pulse oximeter will be measured in percentage
Changes from Baseline in vital signs: Heart rate
时间窗: From Day 1 to Day 7, Day 30, Day 90 and Day 365
Heart rate will be measured as number of beats per minute (bpm)
Changes from Baseline in vital signs: Respiratory rate
时间窗: From Day 1 to Day 7, Day 30, Day 90 and Day 365
Respiratory rate will be measured as number of breaths taken per minute (Breaths/min) .
Changes from Baseline in vital signs: Diastolic Blood Pressure
时间窗: From Day 1 to Day 7, Day 30, Day 90 and Day 365
Diastolic blood pressure will be measured in mmHg
Changes from Baseline in vital signs: Systolic blood pressure
时间窗: : From Day 1 to Day 7, Day 30, Day 90 and Day 365
Systolic blood pressure will be measured in mmHg
Safety measures: electrocardiograms (ECG)
时间窗: Day 7, Day 30, Day 90 and Day 365
Cardiac dysfunction will be monitored by 12-lead ECGs. Abnormal or normal readings will be evaluated
Safety measures: Laboratory results
时间窗: Day 1, Day 3, Day 6, Day 7, Day 30, Day 90 and Day 365
Abnormal or normal laboratory test results (biochemistry, hematology, coagulation, and urinalysis) will be evaluated
次要结局
- Severity of ARDS(Up to 12 months)
- Death rate(Day 7, Day 14 and Day 365)
- Average hospital stays (in days)(Up to 12 months)
- Participants requiring admission to Intensive Care Unit (ICU)(Up to 12 months)
- Duration of ICU stay(Up to 12 months)
- Thorax radiological findings(Day 7 and Day 10 Up to 12 months)
- Oximetry levels(Up to 12 months)
- Overall survival (in days)(Up to 12 months)
- Time to progression (in days)(Up to 12 months)
- Need for invasive mechanical ventilation(Up to 12 months)
- Time to invasive mechanical ventilation (in days)(Up to 12 months)
- Death rate(Day 7, Day 14 and Day 365)
- Average hospital stays (in days)(Up to 12 months)
- Participants requiring admission to Intensive Care Unit (ICU)(Up to 12 months)