Efficacy and Safety Study of HLCM051(MultiStem®) for Pneumonic Acute Respiratory Distress Syndrome

NCT03807804 | Completed Phase 2

• 1 other identifier: B04-02
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 29

Brief Summary

The primary object of this clinical study is to investigate the efficacy of HLCM051 in patients with ARDS caused by pneumonitis.

Conditions

Respiratory Distress Syndrome, Adult

Outcome Measures

Primary Outcomes (35)

• Ventilator-free days (VFD)(ARDS caused by pneumonia cohort)

  VFD for 28 days after administration of the investigational product

  28 days after administration of the investigational product

• Adverse events(ARDS caused by COVID-19 cohort)

  The number and rate of adverse events

  From informed consent to 180 days after administration of the investigational product

• Change from baseline in systolic blood pressure(ARDS caused by COVID-19 cohort)

  Change from baseline in systolic blood pressure(mmHg)

  From screening to 180 days after administration of the investigational product

• Change from baseline in diastolic blood pressure(ARDS caused by COVID-19 cohort)

  Change from baseline in diastolic blood pressure(mmHg)

  From screening to 180 days after administration of the investigational product

• Change from baseline in pulse rate(ARDS caused by COVID-19 cohort)

  Change from baseline in pulse rate(beats/min)

  From screening to 180 days after administration of the investigational product

• Change from baseline in respiration(ARDS caused by COVID-19 cohort)

  Change from baseline in respiration(breath/min)

  From screening to 180 days after administration of the investigational product

• Change from baseline in oxygen saturation(ARDS caused by COVID-19 cohort)

  Change from baseline in oxygen saturation(%)

  From screening to 180 days after administration of the investigational product

• Change from baseline in body temperature(ARDS caused by COVID-19 cohort)

  Change from baseline in body temperature(C)

  From screening to 180 days after administration of the investigational product

• Change from baseline in red blood cell count(ARDS caused by COVID-19 cohort)

  Change from baseline in red blood cell count(/uL)

  From screening to 180 days after administration of the investigational product

• Change from baseline in hemoglobin(ARDS caused by COVID-19 cohort)

  Change from baseline in hemoglobin(g/dL)

  From screening to 180 days after administration of the investigational product

• Change from baseline in hematocrit(ARDS caused by COVID-19 cohort)

  Change from baseline in hematocrit(%)

  From screening to 180 days after administration of the investigational product

• Change from baseline in leukocyte count(ARDS caused by COVID-19 cohort)

  Change from baseline in leukocyte count(/uL)

  From screening to 180 days after administration of the investigational product

• Change from baseline in neutrophils(ARDS caused by COVID-19 cohort)

  Change from baseline in neutrophils(%)

  From screening to 180 days after administration of the investigational product

• Change from baseline in eosinophils(ARDS caused by COVID-19 cohort)

  Change from baseline in eosinophils(%)

  From screening to 180 days after administration of the investigational product

• Change from baseline in basophils(ARDS caused by COVID-19 cohort)

  Change from baseline in basophils(%)

  From screening to 180 days after administration of the investigational product

• Change from baseline in lymphocytes(ARDS caused by COVID-19 cohort)

  Change from baseline in lymphocytes(%)

  From screening to 180 days after administration of the investigational product

• Change from baseline in monocytes(ARDS caused by COVID-19 cohort)

  Change from baseline in monocytes(%)

  From screening to 180 days after administration of the investigational product

• Change from baseline in platelet count(ARDS caused by COVID-19 cohort)

  Change from baseline in platelet count(/uL)

  From screening to 180 days after administration of the investigational product

• Change from baseline in asparate aminotransferase(AST)(ARDS caused by COVID-19 cohort)

  Change from baseline in asparate aminotransferase(AST)(IU/L)

  From screening to 180 days after administration of the investigational product

• Change from baseline in alanine aminotransferase(ALT)(ARDS caused by COVID-19 cohort)

  Change from baseline in alanine aminotransferase(ALT)(IU/L)

  From screening to 180 days after administration of the investigational product

• Change from baseline in alkaline phosphatase(ALP)(ARDS caused by COVID-19 cohort)

  Change from baseline in alkaline phosphatase(ALP)(IU/L)

  From screening to 180 days after administration of the investigational product

• Change from baseline in total bilirubin(ARDS caused by COVID-19 cohort)

  Change from baseline in total bilirubin(mg/dL)

  From screening to 180 days after administration of the investigational product

• Change from baseline in blood urea nitrogen(BUN)(ARDS caused by COVID-19 cohort)

  Change from baseline in blood urea nitrogen(BUN)(mg/dL)

  From screening to 180 days after administration of the investigational product

• Change from baseline in creatinine(ARDS caused by COVID-19 cohort)

  Change from baseline in creatinine(mg/dL)

  From screening to 180 days after administration of the investigational product

• Change from baseline in sodium(Na)(ARDS caused by COVID-19 cohort)

  Change from baseline in sodium(Na)(mmol/L)

  From screening to 180 days after administration of the investigational product

• Change from baseline in potassium(K)(ARDS caused by COVID-19 cohort)

  Change from baseline in potassium(K)(mmol/L)

  From screening to 180 days after administration of the investigational product

• Change from baseline in chloride(Cl)(ARDS caused by COVID-19 cohort)

  Change from baseline in chloride(Cl)(mmol/L)

  From screening to 180 days after administration of the investigational product

• Change from baseline in calcium(Ca)(ARDS caused by COVID-19 cohort)

  Change from baseline in calcium(Ca)(mg/dL)

  From screening to 180 days after administration of the investigational product

• Change from baseline in blood sugar(ARDS caused by COVID-19 cohort)

  Change from baseline in blood sugar(mg/dL)

  From screening to 180 days after administration of the investigational product

• Change from baseline in urinary protein(ARDS caused by COVID-19 cohort)

  Change from baseline in urinary protein(- to \>= 4+)

  From screening to 180 days after administration of the investigational product

• Change from baseline in urinary sugar(ARDS caused by COVID-19 cohort)

  Change from baseline in urinary sugar(- to \>= 4+)

  From screening to 180 days after administration of the investigational product

• Change from baseline in uric blood(ARDS caused by COVID-19 cohort)

  Change from baseline in uric blood(- to \>= 4+)

  From screening to 180 days after administration of the investigational product

• Change from baseline in urinary sediment(RBC)(ARDS caused by COVID-19 cohort)

  Change from baseline in urinary sediment(RBC)(/HPF)

  From screening to 180 days after administration of the investigational product

• Change from baseline in urinary sediment(WBC)(ARDS caused by COVID-19 cohort)

  Change from baseline in urinary sediment(WBC)(/HPF)

  From screening to 180 days after administration of the investigational product

• Change from baseline in urinary sediment(Other)(ARDS caused by COVID-19 cohort)

  Change from baseline in urinary sediment(Other)(/HPF)

  From screening to 180 days after administration of the investigational product

Study Arms (3)

HLCM051 group【ARDS caused by pneumonia cohort】

EXPERIMENTAL

* Patients will receive the standard therapy * A single, one-time dose of HLCM051 9.0×108 (±20%) cells are intravenously infused as a naturally dropped single dose over 30 to 60 minutes at the maximum infusion speed of 10 mL/minute

Biological: HLCM051

Standard treatment group【ARDS caused by pneumonia cohort】

NO INTERVENTION

•Patients will receive the standard therapy

HLCM051 group【ARDS caused by COVID-19 cohort 】

EXPERIMENTAL

* Patients will receive the standard therapy * A single, one-time dose of HLCM051 9.0×108 (±20%) cells are intravenously infused as a naturally dropped single dose over 30 to 60 minutes at the maximum infusion speed of 10 mL/minute

Biological: HLCM051

Interventions

HLCM051 BIOLOGICAL

HLCM051 is the stem cell product that can be mass-produced, being derived from adult adhesive stem cells that were taken from bone marrow of healthy unrelated donors from whom the informed consent was obtained, and proliferated ex vivo.

HLCM051 group【ARDS caused by COVID-19 cohort 】; HLCM051 group【ARDS caused by pneumonia cohort】

Eligibility Criteria

• Age: 20 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of informed consent by the patient or his/her legal representative in case the patient is incapable of giving consent due to sedation etc
• Male or female aged 20 to 90 years at informed consent (Asians only)
• Patients with ARDS caused by pneumonia of those who were diagnosed as having ARDS according to the Berlin Definition
• Patients who are confirmed to have the following findings in the Berlin Definition within the same 24 hours 1)PaO2/FiO2 (P/F) ratio ≤ 300 mmHg with positive end-expiratory pressure (PEEP) ≥ 5 cmH2O 2)Bilateral opacities on chest X-ray or CT (not fully explained by effusions, lobar/lung collapse, and nodular shadow) 3)Respiratory failure that cannot be explained by cardiac failure and fluid overload
• Patients who underwent chest high-resolution computed tomography (HRCT)
• Patients with HRCT score ≥211 according to the abbreviated HRCT scoring system
• Patients with APACHE II score \<27 at the diagnosis of ARDS
• Patients who underwent artificial respiration with intubation
• Patients who can start receiving the investigational product within 72 hours (3 days) after the diagnosis of ARDS
• Patients whose condition is expected to be stable for at least 4 hours after initiating investigational product administration "Stable" means the condition where there is no need for significant sustained increase in FiO2 or PEEP and the supportive care for the cardiovascular system is not required (e.g. an increase in the dose of norepinephrine or epinephrine by ≥0.1 mcg/kg/min or an increase in the dose of inotropic agent or vasopressor by ≥20% besides norepinephrine and epinephrine for blood pressure control)
• Women who are neither pregnant, breastfeeding, planning to become pregnant during the study period. Women of childbearing potential must agree on the use of appropriate contraceptive methods under the guidance of investigators through the completion of the clinical study
• Male patients who have female partners of childbearing potential must agree on the use of appropriate contraceptive methods under the guidance of investigators through the completion of the clinical study

You may not qualify if:

• Patients without life expectancy of 48 hours
• Patients who are under artificial dialysis at screening
• Patients whose life expectancy is \<6 months because of complications at screening
• Patients under ventilator at home due to chronic respiratory disease
• Patients who have been on mechanical ventilation for ≥ 1 week
• Patients with obvious honeycomb lung at screening consistent with pre-existing late-stage interstitial lung disease
• Patients with clinically evident findings consistent with diffuse alveolar hemorrhage
• Patients with chronic respiratory disease that requires continuous domiciliary oxygen therapy
• Patients with severe COPD (stage III or severe according to the GOLD Classification)
• Patients with chronic pulmonary hypertension (class III or IV according to the World Health Organization Classification of Functional Status of Patients With Pulmonary Hypertension)
• Patients with a history of lung lobectomy, single-lung pneumonectomy or pulmonary transplantation
• Patients who are appropriate to be treated with extracorporeal membrane oxygenation (ECMO) at screening
• Patients who were resuscitated after cardio-respiratory arrest
• Patients with a history of ST-segment elevation myocardial infarction within 6 months before informed consent
• Patients with mean arterial (blood) pressure (MAP) \<60 mmHg despite treatment with one or more vasopressor or cardiotonic agent

Sponsors & Collaborators

• Healios K.K.: lead

Study Sites (29)

Investigational Site Number 027

Nagoya, Aichi-ken, Japan

Location

Investigational Site Number 028

Nagoya, Aichi-ken, Japan

Location

Investigational Site Number 005

Seto, Aichi-ken, Japan

Location

Investigational Site Number 020

Toyoake, Aichi-ken, Japan

Location

Investigational Site Number 003

Hirosaki, Aomori, Japan

Location

Investigational Site Number 007

Iizuka, Fukuoka, Japan

Location

Investigational Site Number 019

Ōgaki, Gifu, Japan

Location

Investigational Site Number 011

Sapporo, Hokkaido, Japan

Location

Investigational Site Number 010

Kobe, Hyōgo, Japan

Location

Investigational Site Number 013

Kobe, Hyōgo, Japan

Location

Investigational Site Number 017

Takarazuka, Hyōgo, Japan

Location

Investigational Site Number 025

Yokohama, Kanagawa, Japan

Location

Investigational Site Number 029

Yokohama, Kanagawa, Japan

Location

Investigational Site Number 018

Kashihara, Nara, Japan

Location

Investigational Site Number 026

Suita, Osaka, Japan

Location

Investigational Site Number 022

Ōtsu, Shiga, Japan

Location

Investigational Site Number 014

Izumo, Shimane, Japan

Location

Investigational Site Number 024

Bunkyō-Ku, Tokyo, Japan

Location

Investigational Site Number 021

Chuo Ku, Tokyo, Japan

Location

Investigational Site Number 009

Itabashi-ku, Tokyo, Japan

Location

Investigational Site Number 006

Minato-Ku, Tokyo, Japan

Location

Investigational Site Number 004

Shinagawa-Ku, Tokyo, Japan

Location

Investigational Site Number 008

Shinjuku-Ku, Tokyo, Japan

Location

Investigational Site Number 023

Shinjuku-Ku, Tokyo, Japan

Location

Investigational Site Number 012

Hiroshima, Japan

Location

Investigational Site Number 001

Kumamoto, Japan

Location

Investigational Site Number 002

Kyoto, Japan

Location

Investigational Site Number 015

Nagasaki, Japan

Location

Investigational Site Number 016

Saga, Japan

Location

Related Publications (1)

• Ichikado K, Kotani T, Kondoh Y, Imanaka H, Johkoh T, Fujimoto K, Nunomiya S, Kawayama T, Sawada M, Jenkins E, Tasaka S, Hashimoto S. Clinical efficacy and safety of multipotent adult progenitor cells (invimestrocel) for acute respiratory distress syndrome (ARDS) caused by pneumonia: a randomized, open-label, standard therapy-controlled, phase 2 multicenter study (ONE-BRIDGE). Stem Cell Res Ther. 2023 Aug 22;14(1):217. doi: 10.1186/s13287-023-03451-z.

  PMID: 37608287 DERIVED

MeSH Terms

Conditions

Respiratory Distress Syndrome

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Respiration Disorders

Study Officials

• Kazuya Ichikado, M.D., Ph.D.

  Saiseikai Kumamoto Hospital

  PRINCIPAL INVESTIGATOR

• Satoru Hashimoto, M.D., Ph.D.

  University Hospital, Kyoto Prefectural University of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 【ARDS caused by pneumonia cohort】Parallel Assignment 【ARDS caused by COVID-19 cohort】Single group

Study Record Dates

• First Submitted: January 8, 2019
• First Posted: January 17, 2019
• Study Start: January 1, 2019
• Primary Completion: December 14, 2021
• Study Completion: December 14, 2021
• Last Updated: January 17, 2024

Record last verified: 2021-04

Locations

JP (29)