Study of Human Bone Marrow Mesenchymal Stem Cells in APAP

An Open-label Phase IIa Study to Evaluate the Safety and Preliminary Efficacy of HBMMSC Injection in the Treatment of APAP

The purpose of this open-label phase IIa clinical trial study is to evaluate the safety and preliminary efficacy of hBMMSC intravenous treatment in patients with aPAP.

Study Overview

• Status: Active, not recruiting
• Conditions: Autoimmune Pulmonary Alveolar Proteinosis
• Intervention / Treatment: Drug: human Bone Marrow Mesenchymal Stem Cell (hBMMSC)

Detailed Description

Autoimmune pulmonary alveolar proteinosis (aPAP) is a rare lung disease for which there is no specific drug treatment. Currently, the standard treatment strategy for PAP is whole-lung lavage (WLL), which is invasive and has limited therapeutic efficacy. The purpose of this study is to evaluate the safety and preliminary efficacy of hBMMSC intravenous treatment in patients with aPAP. The clinical trial intends to involve 10 participants. The trial is expected to last approximately 2 years.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • daxing
    • Beijing, daxing, China, 100021
      • JiuzhitangMakerBeijingCellTech

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female aged 18 years or older
• Patients diagnosed with aPAP by both CT and biopsy (TBLB, TBCB, or surgical lung biopsy) or bronchoalveolar perfusion (BAL) as well as GM-CSF autoantibodies in serum positive
• No remission was demonstrated by CT, pulmonary function test results,or blood gas analysis at least 2 times (at least 3 months apart) before enrollment
• At rest PaO2≤70 mmHg
• Fertile participants must receive effective medical contraception (for both male and female participants, up to one year after the last study dosing)
• Voluntary signed informed consent

Exclusion Criteria:

• Diagnosed with hereditary PAP, secondary PAP, or another type of PAP
• Received whole lung lavage（WLL） therapy within 6 months before enrollment
• Received previous GM-CSF therapy within 6 months before enrollment
• Received other clinical trial treatment within 3 months before enrollment
• Participated in other stem cell studies within 1 year before enrollment
• Inflammatory disease or autoimmune disorder requiring treatment associated with significant immunosuppression (e.g. more than 10 mg/day systemic prednisolone)
• Active infection (viral, bacterial, fungal or mycobacterial), which may affect the assessment of efficacy in the trial
• History of malignant tumors
• Known allergic reactions to any of the ingredients in the study drug
• Participants who, in the opinion of the investigator, would aggravate any other serious pre-existing medical condition are not suitable for this trial
• Women who are known to be pregnant, breastfeeding, have a positive pregnancy test (which will be detected during the screening process), or plan to become pregnant during the trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental: hBMMSC; 1.0×10^6/kg hBMMSC (participant's body weight) single dose 2.0×10^6/kg hBMMSC (participant's body weight) single dose 2.0×10^6/kg hBMMSC (participant's body weight) administered twice	Drug: human Bone Marrow Mesenchymal Stem Cell (hBMMSC); Group 1: 1.0×10^6 cells/kg (participant's body weight) single dose (n=3) Group 2: 2.0×10^6 cells/kg (participant's body weight) single dose (n=3) Group 3: 2.0×10^6 cells/kg (participant's body weight) administered twice (n=4); Other Names: hBMMSC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Alveolar-arterial difference in oxygen tension (A-aDO2)	The changes of alveolar-arterial difference in oxygen tension (A-aDO2) relative to baseline were assessed in the hBMMSC treated group after 24 weeks of treatment.	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability	Number of participants with serious and non-serious adverse events	48 weeks
Alveolar-arterial oxygen difference (A-aDO2)	Change from Baseline in the A-aDO2 as measured	48 weeks
Difference in 6-minute walk distance (6MWD)	Change from Baseline in the 6MWD as measured	4 weeks, 12 weeks, 24 weeks, 48 weeks
Percutaneous arterial oxygen saturation (SpO2)	Change from Baseline in the SpO2 as measured	4 weeks, 12 weeks, 24 weeks, 48 weeks
Difference in modified Medical Research Council（mMRC）	Change from Baseline in the mMRC as tested	4 weeks, 12 weeks, 24 weeks, 48 weeks
Difference in St. George's Respiratory Questionnaire（SGRQ）	Change from Baseline in the SGRQ as tested	4 weeks, 12 weeks, 24 weeks, 48 weeks
Imaging（Chest CT score ）	Parenchymal lung density determined by quantitative computed tomography (CT) densitometry. Change from Baseline (Day 0) in the parenchymal densitometry as measured at 24 and 48 weeks	24 weeks, 48 weeks
Difference in Disease severity score (DSS)	Change from Baseline in the DSS score	24 weeks, 48 weeks
Difference in arterial partial pressure of oxygen (PaO2)	Change from Baseline in the PaO2 as measured	24 weeks, 48 weeks
Difference in Krebs Von den Lungen-6（KL-6）	Change from Baseline in the KL-6 as measured	2 weeks，4 weeks, 12 weeks, 24 weeks
Difference in carcinoembryonic antigen（CEA）	Change from Baseline in the CEA as measured	2 weeks，4 weeks, 12 weeks, 24 weeks
Difference in lactate dehydrogenase (LDH)	Change from Baseline in the LDH as measured	2 weeks，4 weeks, 12 weeks, 24 weeks
Number of Rescue whole lung lavage (WLL) in 108 weeks	Criteria for performing WLL were based on symptoms, decreased exercise capacity, and/or worsening of clinical symptoms of aPAP as judged by the investigator that the participant developed hypoxemia or decreased oxygen saturation	108 weeks
Difference in pulmonary function	Pulmonary function tests include diffusing capacity of the lung for carbon monoxide(DLCO),forced vital capacity(FVC), forced expiratory volume in one second(FEV1).Change from Baseline in the DLCO、FVC、 FEV1 as measured	4 weeks, 12 weeks, 24 weeks, 48 weeks

Collaborators and Investigators

• Sponsor: Jiuzhitang Maker (Beijing) Cell Technology Co.,Ltd.
• Collaborators: The First Affiliated Hospital of Guangzhou Medical University

Study record dates

Study Major Dates

• Study Start (Actual): December 25, 2023
• Primary Completion (Estimated): July 22, 2025
• Study Completion (Estimated): August 30, 2026

Study Registration Dates

• First Submitted: October 19, 2023
• First Submitted That Met QC Criteria: October 26, 2023
• First Posted (Actual): November 1, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 19, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Pulmonary Alveolar Proteinosis
• Other Study ID Numbers: MKMSC-CT-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No