Study on Safety and Efficacy of Two Doses of PRS CK STORM in the Modulation of the Cytokine Storm for the Treatment of Acute Respiratory Distress Syndrome (ARDS) Caused by SARS-Cov-2, Influenza A, Influenza B and Respiratory Syncytial Virus (RSV)

NCT06684379 | Recruiting Phase 1

• 2 other identifiers: PRSCK-21P012023-507700-32-00
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

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 Monocytes and fat-derived Mesenchymal Stromal Cells (PRS CK STORM) in the modulation of the cytokine storm for the treatment of the acute respiratory distress syndrome (ARDS) caused by SARS-Cov-2, influenza A, influenza B and respiratory syncytial virus (RSV) in recently hospitalized participants (less than 3 days) 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 for the treatment of ARDS 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 ARDS-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 hospitalized for ARDS 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 ARDS 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.

Conditions

SARS-CoV-2; Influenza, Human; Respiratory Syncytial Virus Infections; Respiratory Distress Syndrome

Keywords

SARS-CoV-2 infection; Causing atypical respiratory disease (COVID-19); 2019 Novel Coronavirus; COVID-19 Virus; SARS Coronavirus 2; COVID-19-associated cytokine storm; Lung Diseases; Pneumonia; M2-macrophages; Mesenchymal cells; Influenza A Virus; Influenza B Virus; RSV Infection; Acute Respiratory Distress Syndrome; ARDS, Human; Respiratory Distress Syndrome, Acute; Cytokine storm

Outcome Measures

Primary Outcomes (12)

• Adverse Events (AEs)

  Number and proportion of subjects experiencing AEs.

  Up to 12 months

• Serious adverse events (SAEs)

  Number and proportion of subjects experiencing SAEs

  Up to 12 months

• Treatment-emergent adverse events (TEAEs)

  Number and proportion of subjects experiencing TEAEs

  Up to 12 months

• Safety measures: Clinical evaluation through physical examination

  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

  Day 7, Day 30, Day 90 and Day 365

• Changes from Baseline in vital signs: body temperature

  Body Temperature of participants will be measure d in Celsius (ºC)

  From Day 1 to Day 7, Day 30, Day 90 and Day 365

• Changes from Baseline in vital signs: oximetry

  Levels of blood oxygen saturation (SpO2) using a pulse oximeter will be measured in percentage

  From Day 1 to Day 7, Day 30, Day 90 and Day 365

• Changes from Baseline in vital signs: Heart rate

  Heart rate will be measured as number of beats per minute (bpm)

  From Day 1 to Day 7, Day 30, Day 90 and Day 365

• Changes from Baseline in vital signs: Respiratory rate

  Respiratory rate will be measured as number of breaths taken per minute (Breaths/min) .

  From Day 1 to Day 7, Day 30, Day 90 and Day 365

• Changes from Baseline in vital signs: Diastolic Blood Pressure

  Diastolic blood pressure will be measured in mmHg

  From Day 1 to Day 7, Day 30, Day 90 and Day 365

• Changes from Baseline in vital signs: Systolic blood pressure

  Systolic blood pressure will be measured in mmHg

  : From Day 1 to Day 7, Day 30, Day 90 and Day 365

• Safety measures: electrocardiograms (ECG)

  Cardiac dysfunction will be monitored by 12-lead ECGs. Abnormal or normal readings will be evaluated

  Day 7, Day 30, Day 90 and Day 365

• Safety measures: Laboratory results

  Abnormal or normal laboratory test results (biochemistry, hematology, coagulation, and urinalysis) will be evaluated

  Day 1, Day 3, Day 6, Day 7, Day 30, Day 90 and Day 365

Secondary Outcomes (11)

• 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

Other Outcomes (2)

• Variations in anti-inflamatory cytokine levels

  Day 1, Day 3 and Day 6

• Variation in pro-inflammatory cytokine levels

  Day 1, Day 3 and Day 6

Study Arms (3)

Saline Solution 0,9% for injection

ACTIVE COMPARATOR

Participants will receive a single 10 mL dose Intravenous (IV) infusion of normal saline (0.9%)

Drug: Placebo comparator

PRS CK STORM - dose A

EXPERIMENTAL

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

Drug: PRS CK STORM

PRS CK STORM - dose B

EXPERIMENTAL

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.

Drug: PRS CK STORM

Interventions

Placebo comparator DRUG

A single dose of saline solution 0.9% for infusion

Also known as: Saline Solution

Saline Solution 0,9% for injection

PRS CK STORM DRUG

A single dose of PRS CK STORM (dose A) for infusion

PRS CK STORM - dose A

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent by the patient 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.
• Hospitalized patients with a diagnosis of ARDS confirmed by Berlin criteria.
• 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.
• Participants to be hospitalized or who have been admitted for less than 3 days and who have had symptoms up to a maximum of 10 days prior to screening.
• 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.

You may not qualify if:

• Failure to perform screening or baseline examinations.
• Body Mass Index (BMI) more than or equal to 35.
• Irreversible critical condition.
• Active autoimmune diseases or severe immunosuppression.
• 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: 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 60 (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 except skin malignancies (other than melanoma) or indolent prostate cancer
• 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 \[HCV ribonucleic acid (RNA) detectable in any subject with positive anti-HCV antibody (HCV Ab)\].
• Other serious active viral infections apart from SARS-CoV-2, influenza A, influenza B or RSV that require specific antimicrobial treatment.

Sponsors & Collaborators

• PEACHES BIOTECH: lead

Study Sites (1)

Hospital Universitario de Fuenlabrada

Fuenlabrada, Madrid, 28942, Spain

RECRUITING

Related Publications (4)

• Lapuente JP, Gomez G, Marco-Brualla J, Fernandez P, Desportes P, Sanz J, Garcia-Gil M, Bermejo F, San Martin JV, Algaba A, De Gregorio JC, Lapuente D, De Gregorio A, Lapuente B, Gomez S, Andres MLV, Anel A. Evaluation in a Cytokine Storm Model In Vivo of the Safety and Efficacy of Intravenous Administration of PRS CK STORM (Standardized Conditioned Medium Obtained by Coculture of Monocytes and Mesenchymal Stromal Cells). Biomedicines. 2022 May 8;10(5):1094. doi: 10.3390/biomedicines10051094.

  PMID: 35625831 BACKGROUND

• Centro de Coordinación y Alertas Sanitarias (coord.). Manejo clínico del COVID-19: atención hospitalaria. Madrid: Ministerio de Sanidad; 2020.

  BACKGROUND

• Clinical practice guidelines for influenza [Internet]. Geneva: World Health Organization; 2024. Available from http://www.ncbi.nlm.nih.gov/books/NBK607904/

  PMID: 39374347 BACKGROUND

• Lapuente JP, Blazquez-Martinez A, Marco-Brualla J, Gomez G, Desportes P, Sanz J, Fernandez P, Garcia-Gil M, Bermejo F, San Martin JV, Algaba A, De Gregorio JC, Lapuente D, De Gregorio A, Lapuente B, Andres MV, Anel A. Cytokine Profile and Anti-Inflammatory Activity of a Standardized Conditioned Medium Obtained by Coculture of Monocytes and Mesenchymal Stromal Cells (PRS CK STORM). Biomolecules. 2022 Mar 31;12(4):534. doi: 10.3390/biom12040534.

  PMID: 35454123 RESULT

MeSH Terms

Conditions

Influenza, Human; Respiratory Syncytial Virus Infections; Respiratory Distress Syndrome; COVID-19; Lung Diseases; Pneumonia; Cytokine Release Syndrome

Interventions

Saline Solution

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Pneumovirus Infections; Paramyxoviridae Infections; Mononegavirales Infections; Respiration Disorders; Pneumonia, Viral; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• David Bernal, Dr.

  Hospital Universitario de Fuenlabrada

  PRINCIPAL INVESTIGATOR

• Guillermo Soria Fernández-Llamazares, Dr

  Hospital Universitario de Fuenlabrada

  STUDY CHAIR

Central Study Contacts

Francesca Sarno, Dr.

CONTACT

+34 674 747 199; francesca.sarno@livingcells.org

Juan Carlos de Gregorio

CONTACT

+34 607964152; jcg@peaches.es

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Subjects will be randomized in blocks; the study will be conducted in 2 parts in sequential groups of two increasing doses of PRS CK STORM (A and B) and consecutively evaluated in 2 sentinel groups of 4 patients. Patients will be randomized to receive treatment in groups of 2, for 5 consecutive days, until 48 hours after the last drug administration (short-term safety follow-up period).

Study Record Dates

• First Submitted: October 23, 2024
• First Posted: November 12, 2024
• Study Start: October 2, 2024
• Primary Completion (Estimated): October 2, 2026
• Study Completion (Estimated): October 2, 2026
• Last Updated: August 7, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)