Treatment of Idiopathic Pulmonary Fibrosis(IPF) by REGEND001

An Open-labelled Clinical Study to Explore the Safety, Tolerability and Preliminary Efficacy of REGEND001 Autologous Therapy Product for Treatment of Idiopathic Pulmonary Fibrosis (IPF).

Idiopathic pulmonary fibrosis (IPF) is a serious chronic (long term) disease with injury of lung tissues. REGEND001 Autologous Therapy Product, made from bronchial basal cells with ability to regenerate lung tissue, is promising to IPF treatment. In this study, a single-armed clinical trial is ongoing to assess the safety and tolerability of REGEND001 Autologous Therapy Product in treatment of IPF. Different doses of REGEND001 Autologous Therapy Product is evaluated to establish a dose-response relationship and to recommend appropriate dose for subsequent clinical trials.

Study Overview

• Status: Completed
• Conditions: Idiopathic Pulmonary Fibrosis
• Intervention / Treatment: Drug: REGEND001 Autologous Therapy Product

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Zuojun Xu, M.D.; Phone Number: 86-10-69156114; Email: xuzj@hotmail.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China
      • Peking Union Medical College Hospital, Chinese Academy of Medical Sciences
  • Guangdong
    • Guangzhou, Guangdong, China
      • The First Affiliated Hospital of Guangzhou Medical University
  • Shanghai
    • Shanghai, Shanghai, China
      • Ruijin Hospital, Shanghai Jiao Tong University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 48 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female, aged between 50 to 75;
• Subjects diagnosed with IPF according to guidelines for the diagnosis of idiopathic pulmonary fibrosis 2018 edition;
• Subjects with 30%~79% of the predicted value in diffusing capacity for carbon monoxide (DLCO) and more than 50% of the predicted value in forced vital capacity (FVC) in pulmonary function tests 3 months before screening;
• Subjects with typical High-resolution computed tomography (HR-CT) imaging findings of idiopathic pulmonary fibrosis in the past 12 months;
• Subjects tolerant to bronchofiberscope;
• Subjects fully informed of the purpose, method and possible discomfort of the trial, agreeing to participate in the test, and voluntarily signing the informed consent;
• Subjects with good adherence, willingness to take medication and regular follow-up examinations as required by the protocol ；
• Subjects able to understand and cooperate with the completion of pulmonary function tests.

Exclusion Criteria:

• Subjects who cannot tolerate cell therapy
• Pregnant or lactating women;
• Subjects with syphilis or any of human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV) positive antibody; Of which stable HBV carriers after drug treatment (DNA titer ≤500 IU/mL or copy number <1000 copies/mL) and cured hepatitis C patients (HCV RNA is negative) can be enrolled；
• Subjects with malignant tumors or a history of malignant tumors;
• Subjects with taking drugs which caused lung fibroblast such as amiodarone in a long term before screening;
• Subjects with infections in lung or other site, including bacterial and viral infections, requiring intravenous treatment before cell transplantation;
• Subjects with a history of invasive or noninvasive mechanical ventilation within 4 weeks;
• Subjects with any of the following lung diseases: asthma, active tuberculosis, pulmonary embolism, pneumothorax, pulmonary hypertension, pneumoconiosis, etc.; lung cancer, bronchiolitis obliterans or other active lung disease; Pneumonia currently or within the last 4 weeks; Pneumonectomy Previously;
• Subjects needing oxygen therapy currently (oxygen therapy time> 15h/d);
• Subjects suffering from serious other systemic diseases, such as myocardial infarction, unstable angina, liver cirrhosis, acute glomerulonephritis, connective tissue disease, etc.;
• Subjects with following results : leukopenia (leukopenia < 4×10^9/L) or agranulocytosis (leukocyte < 1.5×10^9/L or neutrophils < 0.5×10^9/L) of any cause; Blood creatinine > 2.5 times the upper limit of normal; Alanine transaminase (ALT) and Aspartate transaminase (AST) > 2.5 times the upper limit of normal values in the laboratory tests.
• Subjects with a history of mental illness or suicide risk, epilepsy or other central nervous system disorders
• Subjects with severe arrhythmias (such as ventricular tachycardia, frequent supraventricular tachycardia, atrial fibrillation, atrial flutter, etc.) or atrioventricular block of degree II or above, shown by 12-lead Electrocardiogram (ECG);
• Subjects with a history of abusing alcohol and illicit drug;
• Subjects who are allergic to cattle products;
• Subjects who participated in other clinical trials in the past 3 months;
• Subjects with poor compliance and difficult to complete the investigation;
• Investigators, employees of research centers or family members of them (none of whom are suitable to participate in the trial to ensure the objectivity of the research);
• Subjects who had an acute exacerbation of IPF or hospitalized for other respiratory diseases 3 or more times in the past 1 year;
• Subjects who take nintedanib for medication within 1 month, or plan to continue taking nintedanib for medication;
• Subjects with other acquired or congenital immunodeficiency disorders, or with a history of organ transplantation or cell transplant therapy;
• Subjects whose expected survival may be less than one year judged by the investigator;
• Male participants of childbearing potential and female participants within childbearing age were reluctant to use effective contraception from the time of signing the informed consent to 6 months after cell therapy;
• Subjects assessed as inappropriate to participate in this clinical trial by investigator.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: REGEND001 autologous bronchial basal cells; Transplantation of autologous bronchial basal cells	Drug: REGEND001 Autologous Therapy Product; Transplantation of REGEND001 Autologous Therapy Product for dosage re-escalation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and severity of the cell therapy-related adverse events (AEs)	Dose escalation is based on incidence of cell therapy-related AEs. Severity of cell therapy-related adverse events (AEs) is evaluated according to Common Terminology Criteria for Adverse Events (CTCAE).	Within 24 weeks after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of complication related to bronchoscopy	REGEND001 Autologous Therapy Product is given to subjects by bronchoscopy. Thus, incidence of complication related to bronchoscopy is adapted to assess the safety of the products.	Within 24 weeks after treatment
Change of lung diffusing capacity for single-breath carbon monoxide (DLCO-sb) from baseline	DLCO-sb is measured by the single-breath method. It is considered a measure of the conductance of CO across the alveolar-capillary membrane and its binding with hemoglobin.	4, 12, and 24 weeks after treatment
Change of forced vital capacity (FVC) from baseline	FVC indicates the volume of air that can forcibly be blown out after full inspiration.	4 weeks after treatment, 12 weeks after treatment and 24 weeks after treatment
Change of the ratio of diffusing capacity for carbon monoxide/ the alveolar volume (DLCO/VA) from baseline	The DLCO test refers to the diffusing capacity for carbon monoxide in the lungs. It's a type of pulmonary function test that helps to assess how well gas is exchanged between the lungs and the bloodstream.Since DLCO is affected by the amount of inhaled gas and lung volume, the subject's alveolar ventilation (VA) should be considered when evaluating diffusion function to exclude the effect of lung volume on diffusion volume.	4 weeks after treatment, 12 weeks after treatment and 24 weeks after treatment
Change of 6-minute-walk test (6MWT) from baseline	The 6MWT is a commonly used test for the objective assessment of functional exercise capacity by testing the distance patients can walk at the fastest speed within 6 minutes.	4 weeks after treatment, 12 weeks after treatment, and 24 weeks after treatment
Change of St. George's respiratory questionnaire (SGRQ) scale from baseline	Quality of life was assessed by St. George's respiratory questionnaire (SGRQ) scale. Total score, ranged from 0 to 100, is the sum of points from all items. A higher value represents a worse outcome.	4 weeks after treatment, 12 weeks after treatment, and 24 weeks after treatment
Change of imaging of lung by high resolution computed tomography (HR-CT)	Images of lung will be analyzed to indicate the newly-derived pulmonary structure.	24 weeks after treatment
Idiopathic pulmonary fibrosis (IPF) exacerbation events	Frequency and severity of IPF exacerbation events will be evaluated.	Within 24 weeks after treatment
Blood routine	Number of cases of participants with abnormal laboratory test results.	Within 24 weeks after treatment.
Urine routine	Number of cases of participants with abnormal laboratory test results.	Within 24 weeks after treatment.
Blood biochemistry	Number of cases of participants with abnormal laboratory test results.	Within 24 weeks after treatment
12-lead Electrocardiogram (ECG)	Number of cases of participants with abnormal 12-lead Electrocardiogram (ECG)	Within 24 weeks after treatment
Carcinoembryonic antigen (CEA)	CEA is a tumor marker used for early diagnosis of lung cancer.	Baseline, 12 weeks after treatment, 24 weeks after treatment
Neuron-specific enolase (NSE)	NSE is a tumor marker significantly elevated in small cell lung cancer.	Baseline, 12 weeks after treatment, 24 weeks after treatment
Cytokeratin-19-fragment (CYFRA21-1)	CYFRA21-1 is a tumor marker which has important value for the pathological classification and prognosis evaluation of lung cancer.	Baseline, 12 weeks after treatment, 24 weeks after treatment
Squamous cell carcinoma antigen (SCC)	SCC is a specific marker for lung squamous cell carcinoma.Tumor markers are monitored to assess the safety.	Baseline, 12 weeks after treatment, 24 weeks after treatment

Collaborators and Investigators

• Sponsor: Regend Therapeutics
• Collaborators: Peking Union Medical College Hospital; Ruijin Hospital; The First Affiliated Hospital of Guangzhou Medical University; Regend Therapeutics XLotus (Jiangxi) Co, Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): July 19, 2021
• Primary Completion (Actual): June 9, 2023
• Study Completion (Actual): June 9, 2023

Study Registration Dates

• First Submitted: November 15, 2022
• First Submitted That Met QC Criteria: December 19, 2022
• First Posted (Actual): December 20, 2022

Study Record Updates

• Last Update Posted (Actual): October 12, 2023
• Last Update Submitted That Met QC Criteria: October 10, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Interstitial; Fibrosis; Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis
• Other Study ID Numbers: XHYX-IND-IPF-P1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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