Clinical trial NCT06111846: Study of Human Bone Marrow Mesenchymal Stem Cells in APAP
Official title: An Open-label Phase IIa Study to Evaluate the Safety and Preliminary Efficacy of HBMMSC Injection in the Treatment of APAP
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Autoimmune Pulmonary Alveolar Proteinosis
Lead sponsor: Jiuzhitang Maker (Beijing) Cell Technology Co.,Ltd.
Sponsor class: OTHER
Collaborators: name: The First Affiliated Hospital of Guangzhou Medical University
First posted: 2023-11-01
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Alveolar-arterial difference in oxygen tension (A-aDO2)
timeFrame: 24 weeks
Secondary outcomes:
measure: Safety and tolerability
timeFrame: 48 weeks
measure: Difference in pulmonary function
timeFrame: 4 weeks, 12 weeks, 24 weeks, 48 weeks
measure: Alveolar-arterial oxygen difference (A-aDO2)
timeFrame: 48 weeks
measure: Difference in 6-minute walk distance (6MWD)
timeFrame: 4 weeks, 12 weeks, 24 weeks, 48 weeks
measure: Percutaneous arterial oxygen saturation (SpO2)
timeFrame: 4 weeks, 12 weeks, 24 weeks, 48 weeks
measure: Difference in modified Medical Research Council（mMRC）
timeFrame: 4 weeks, 12 weeks, 24 weeks, 48 weeks
measure: Difference in St. George's Respiratory Questionnaire（SGRQ）
timeFrame: 4 weeks, 12 weeks, 24 weeks, 48 weeks
measure: Imaging（Chest CT score ）
timeFrame: 24 weeks, 48 weeks
measure: Difference in Disease severity score (DSS)
timeFrame: 24 weeks, 48 weeks
measure: Difference in arterial partial pressure of oxygen (PaO2)
timeFrame: 24 weeks, 48 weeks
measure: Difference in Krebs Von den Lungen-6（KL-6）
timeFrame: 2 weeks，4 weeks, 12 weeks, 24 weeks
measure: Difference in carcinoembryonic antigen（CEA）
timeFrame: 2 weeks，4 weeks, 12 weeks, 24 weeks
measure: Difference in lactate dehydrogenase (LDH)
timeFrame: 2 weeks，4 weeks, 12 weeks, 24 weeks
measure: Number of Rescue whole lung lavage (WLL) in 108 weeks
timeFrame: 108 weeks
Other outcomes:
Locations:
city: Beijing
country: China
facility: JiuzhitangMakerBeijingCellTech
state: daxing
Study officials:
References: