Clinical Study to Assess the Safety and Preliminary Efficacy of HCR040 in Acute Respiratory Distress Syndrome

Phase 1/2 Clinical Study to Assess the Feasibility, Safety, Tolerability and Preliminary Efficacy of the Administration of HCR040, Allogeneic Adipose-derived Adult Mesenchymal Stem Cells, in Acute Respiratory Distress Syndrome

The main objective of the study is to assess the feasibility, safety, and tolerability of the administration of HCR040, a drug whose active substance is HC016, allogeneic adipose-derived adult mesenchymal stem cells expanded and pulsed with H2O2, in patients with acute respiratory distress syndrome.

Study Overview

• Status: Completed
• Conditions: Acute Respiratory Distress Syndrome
• Intervention / Treatment: Drug: HCR040 (Phase 1); Drug: Placebo (Phase 2); Drug: HCR040 (Phase 2)

Detailed Description

HCR040 is an investigational medicinal product whose active substance is HC016, allogeneic adipose-derived adult mesenchymal stem cells expanded and pulsed with H2O2.

The main purpose of this study is to evaluate the safety and tolerability of a single administration of HCR040 using: a) two sequential escalating doses administered 96 hours post-injury to participants with moderate to severe acute respiratory distress syndrome (ARDS); and b) the determined maximum tolerated dose administered 96 hours post-injury to participants with moderate to severe ARDS. The study also includes initial exploration of efficacy.

Treatment is administered by intravenous injection.

The study has been divided into two phases:

Phase 1 (open label): 6 participants with moderate to severe ARDS will be included in 2 sequential cohorts.

Phase 2 (randomized, controlled, double-blind): 20 participants with moderate to severe ARDS will be randomly divided into two groups (control and treated).

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Spain
  • Madrid, Spain, 28040
    • Fundación Jimenez Díaz
  • Bizkaia
    • Barakaldo, Bizkaia, Spain, 48903
      • Hospital Universitario de Cruces

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Men and women ≥ 18 years
• Patients with criteria of moderate to severe ARDS according to the Berlin Conference.
• Berlin criteria of moderate to severe ARDS given simultaneously during the 24 hours prior to entry into the study
• Patients with invasive mechanical ventilation in controlled mode (VC, PC or VCRP) adjusted to Vt≤8 mL/kg, Ppl <30 cmH2O and minimum PEEP of 8 cmH2O

Exclusion Criteria:

• Participation in a previous clinical study within 28 days prior to the ARDS situation
• Administration of a previous cell therapy product in the 5 years prior to this ARDS clinical situation
• Inability to obtain Informed Consent
• Hemodynamic instability that contraindicates the intravenous cellular administration, within the defined time frame for inclusion in the study
• Alveolar hemorrhage or hemoptysis
• LTSV situation (Limitation of life support treatments)
• Major trauma in the previous 5 days
• Neoplastic processes at any time
• EPOC or severe home asthma or any other type of chronic respiratory disease requiring respiratory oxygen
• Known Child-Pugh liver disease score > B9
• Pregnant women or women of childbearing age who are not using an adequate method of contraception, or who, if they are using it, are not willing to continue using it for the duration of the trial. If the patient is menopausal or sterile, it must be documented in the medical record
• Women who are breastfeeding if unwillingly to stop at the time of recruitment
• Pulmonary transplant
• Known grade III or IV pulmonary hypertension
• States of hypercoagulability
• History of DVP or PE in the last 6 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HCR040 (Phase 1); Participants with moderate to severe acute respiratory distress syndrome (6 patients)	Drug: HCR040 (Phase 1); (Phase 1) Intravenous administration. Open label dose escalation, 3 patients in cohort 1 (1 million cells/kg) and 3 patients in cohort 2 (2 million cells/kg); Other Names: Allogeneic adipose-derived adult mesenchymal stem cells expanded and pulsed with H2O2
Placebo Comparator: Control group (Phase 2); Participants with moderate to severe acute respiratory distress syndrome (10 patients)	Drug: Placebo (Phase 2); (Phase 2) Intravenous administration of vehicle solution; Other Names: Saline solution
Experimental: HCR040 (Phase 2); Participants with moderate to severe acute respiratory distress syndrome (10 patients)	Drug: HCR040 (Phase 2); (Phase 2) Intravenous administration of the maximum tolerated dose (1 million cells/kg or 2 million cells/kg); Other Names: Allogeneic adipose-derived adult mesenchymal stem cells expanded and pulsed with H2O2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of adverse events as a measure of safety and tolerability of a single dose of HCR040 when administered by intravenous injection	One year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average stay in the Intensive Care Unit (ICU) 28 days after the administration of HCR040		Day 28
Sequential Organ Failure Assessment (SOFA) index at 3, 7, 14, 21, and 28 days after the administration of HCR040	SOFA index from 0 to 4 where lower scores represent improvement	Day 28
Mechanical ventilation-free days 28 days after the administration of HCR040		Day 28
Percent mortality 28 days after the administration of HCR040		Day 28
Daily pulmonary mechanics values (Ppl, DP, CRS)		One year
Determination of lung damage using the Murray scale at day 3, 7, 14 and 28 after the administration of HCR040	Murray scale from 0 to 4 where lower scores represent improvement	Day 28
Vasopressor-free days 28 days after the administration of HCR040		Day 28
ICU-free days 28 days after the administration of HCR040		Day 28

Collaborators and Investigators

• Sponsor: Histocell, S.L.
• Investigators: Principal Investigator: Fermin Labayen Beraza, MD, Hospital de Cruces

Study record dates

Study Major Dates

• Study Start (Actual): December 10, 2019
• Primary Completion (Actual): August 16, 2021
• Study Completion (Actual): February 27, 2022

Study Registration Dates

• First Submitted: February 26, 2020
• First Submitted That Met QC Criteria: February 26, 2020
• First Posted (Actual): February 28, 2020

Study Record Updates

• Last Update Posted (Actual): February 28, 2024
• Last Update Submitted That Met QC Criteria: February 27, 2024
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: ARDS; cell therapy; Acute Respiratory Distress Syndrome; acute lung injury; mesenchymal stem cells; anti-inflammation; allogenic
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Disease; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; Syndrome; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury; Anti-Infective Agents, Local; Anti-Infective Agents; Hydrogen Peroxide
• Other Study ID Numbers: ALICELL-CT-01; 2019-002688-89 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No