Human Umbilical Cord Mesenchymal Stem Cell Injection for the Treatment of Interstitial Lung Disease

Phase 1

Not yet recruiting

• Conditions: Interstitial Lung Disease
• Interventions: Drug: Human umbilical cord mesenchymal stem cell injection

• Registration Number: NCT06534528
• Lead Sponsor: Shanghai Life Science & Technology

Brief Summary

Main objective: To explore the safety and tolerability of human umbilical cord mesenchymal stem cell injection in the treatment of interstitial lung disease (ILD); Secondary objective: To explore the preliminary effectiveness of human umbilical cord mesenchymal stem cell therapy for interstitial lung disease (ILD) and recommend appropriate cell therapy doses for subsequent clinical studies; Exploring the immunogenicity of human umbilical cord mesenchymal stem cell injection in the treatment of interstitial lung disease (ILD).

Detailed Description

Not available

Study Timeline

• Status Verified: 2024-07
• Study First Submitted: 2024-07-12
• Study First Submitted QC: 2024-07-30
• Last Update Submitted: 2024-07-30
• Study First Posted: 2024-08-02
• Last Update Posted: 2024-08-02
• Study Start: 2024-10-01
• Primary Completion: 2025-10-01
• Study Completion: 2027-10-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

• Gender not limited, age ≥ 18 years old (including threshold);
• Clinical diagnosis of interstitial lung disease;
• Blood biochemistry tests must meet the following criteria: alanine aminotransferase (ALT) ≤ 2.5 × ULN, aspartate aminotransferase (AST) ≤ 2.5 × ULN, total bilirubin (TBIL) ≤ 2 × ULN, direct bilirubin (DBIL) ≤ 1.5 × ULN, or creatinine (Cr) ≤ 3 × ULN;
• The diffusion capacity of carbon monoxide (DLCO) (corrected by Hb) in lung function tests within the previous 3 months is 30% to 80% of the expected value (including 30% and 80%); Forced vital capacity (FVC) is 40% to 70% of the estimated value (including 40% and 70%)

Exclusion Criteria

• Within the first 3 days of enrollment, use high-dose corticosteroids (equivalent to methylprednisolone>240 mg/day) or irregularly use systemic corticosteroids;
• For patients receiving immunosuppressive therapy, unstable background treatment with cyclophosphamide, mycophenolate mofetil/sodium, methotrexate, or other immunosuppressive monotherapy is not allowed (combination therapy is not allowed)
• Diagnose IPF patients who have previously taken drugs that may cause or worsen pulmonary fibrosis;
• Individuals with a history of mechanical ventilation or concurrent infectious pneumonia or asthma within the previous month prior to screening; Patients with airway obstruction disease (FEV1/FVC<0.7 before using bronchodilators); Patients with other clinically significant serious abnormalities in the lungs; Currently requiring oxygen therapy treatment (oxygen therapy time>15h/d);
• Pregnant and lactating women
• Screening for malignant tumors that have occurred within the past 5 years, excluding cervical carcinoma in situ, squamous cell carcinoma of the skin, or basal cell carcinoma that have been previously treated for curative purposes;
• Individuals who have been hospitalized for 3 or more times due to acute exacerbation of ILD or other respiratory diseases within the past year prior to screening
• There is evidence that subjects currently have digestive system, urinary system, cardio cerebrovascular, blood system, nervous system, mental and metabolic diseases that may affect safety, such as type 2 diabetes with poor blood sugar control, hypertension with poor blood pressure control, etc
• have a history of abuse or drug use of psychotropic substances
• individuals allergic to human serum albumin, anesthetics, or their components
• Select participants who have participated in any other clinical trials within the previous 3 months;
• individuals who have previously received stem cell therapy
• Researchers have determined that the expected survival period may be less than 1 year;
• Subjects who cannot tolerate bronchoscopy examination (including but not limited to: active massive hemoptysis; severe hypertension and arrhythmia;

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Dose escalation	Human umbilical cord mesenchymal stem cell injection	Four different doses were set, and three subjects in each dose plan received human umbilical cord mesenchymal stem cell injection successively. Each subject received a single dose of 6.0\*10\^6, 3.0\*10\^7,6.0\*10\^7, and 9.0\*10\^7 cells / person.

Primary Outcome Measures

Name	Time	Method
Maximum tolerated dose per dose (MTD)	From the first administration to 4 weeks after administration	The maximum tolerable dose (MTD) of a single administration depends on whether dose limiting toxicity (DLT) occurs within 4 weeks after the first administration, for example (1) Hematological toxicity of grade 3 and above caused by the treatment of human umbilical cord mesenchymal stem cell injection. There are grade 3 and above non hematological toxic reactions caused by the treatment of human umbilical cord mesenchymal stem cell injection, except for the following cases, (3) Any other toxicity related to cell therapy that is higher than the baseline level is judged as clinically significant and / or unacceptable by the investigator and the sponsor, (4) There are acute exacerbations and serious adverse events (SAE) of IPF related to the treatment of human umbilical cord mesenchymal stem cell injection (which may be related, likely to be related and definitely related)

Secondary Outcome Measures

Name	Time	Method
Preliminary efficacy evaluation：lung function	The 4th, 12th, 24th week after administration	Changes from baseline in lung function (forced vital capacity, diffusion capacity for carbon monoxide) in the treatment of Interstitial lung disease(ILD), and to recommend the appropriate dose of cell therapy for subsequent clinical studies.; Forced vital capacity(FVC) in litre(L); Diffusion capacity for carbon monoxide(DLCO) in ml/min/mmHg
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]：Pulse	The 4th, 12th, 24th week after administration	Pulse in beats per minute
Preliminary efficacy evaluation: St. George's respiratory questionnaire(SGRQ)	The 4th, 12th, 24th week after administration	Changes from baseline in score of St. George's respiratory questionnaire(SGRQ). To study the value of St George s respiratory questionnaire(SGRQ) in evaluating the life quality of patients with ILD, and to recommend the appropriate dose of cell therapy for subsequent clinical studies.; St. George's respiratory questionnaire(SGRQ) score: Range 0-100,The higher the score, the more severe the impact of the disease on symptoms, activities, and daily life.
Preliminary efficacy evaluation: dyspnea score	The 4th, 12th, 24th week after administration	Changes from baseline in value of dyspnea score. To study the value of dyspnea score(modified Medical Research Council, mMRC) in evaluating the life quality of patients with ILD, and to recommend the appropriate dose of cell therapy for subsequent clinical studies.; Dyspnea score(mMRC)：Range 0-4,mMRC levels 0-1 indicate few symptoms, mMRC levels 2-3 indicate multiple symptoms, and level 4 indicates difficulty breathing at the slightest level of activity.
Preliminary efficacy evaluation: cough score	The 4th, 12th, 24th week after administration	Changes from baseline in value of cough score. To study the value of cough score(Cough Evaluation Test, CET) in evaluating the life quality of patients with ILD, and to recommend the appropriate dose of cell therapy for subsequent clinical studies.; Cough score(Cough Evaluation Test, CET)：Range 5-25, the higher the score, the more severe the daytime cough, the greater the impact of nighttime cough on sleep, and the greater the impact of cough on daily life and psychology.
Preliminary efficacy evaluation: 6-minute walk test	The 4th, 12th, 24th week after administration	Changes from baseline in result of 6-minute walk test (grade and distance) in the treatment of Interstitial lung disease(ILD), and to recommend the appropriate dose of cell therapy for subsequent clinical studies.; Draw a straight distance of 30.5 meters (100 feet) on a flat surface, and place a chair at each end as a marker. The subjects walked back and forth between them, with the pace determined by their own physical abilities. The personnel monitoring on the side report the time every 2 minutes and record any discomfort such as shortness of breath or chest pain that the subject may experience.
Preliminary efficacy evaluation: Frequency of acute exacerbation events	The 4th, 12th, 24th week after administration	Changes from baseline in Frequency of acute exacerbation events in the treatment of Interstitial lung disease(ILD), and to recommend the appropriate dose of cell therapy for subsequent clinical studies
Preliminary efficacy evaluation: High Resolution Computed Tomography scores(HRCT score)	The 4th, 12th, 24th week after administration	Changes from baseline in chest High Resolution Computed Tomography scores(Warrick score) in the treatment of Interstitial lung disease(ILD), and to recommend the appropriate dose of cell therapy for subsequent clinical studies.; HRCT score(Warrick score): Range 0-30,the higher the score, the more severe the lesion type and the wider the lesion range.
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]：Blood pressure	The 4th, 12th, 24th week after administration	Blood pressure in millimeter of mercury(mmHg)
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]：respiration rate	The 4th, 12th, 24th week after administration	Respiration rate in times/minute
Blood routine	The 4th, 12th, 24th week after administration	White blood cell count (WBC) in 10\^9/L; Neutrophil count (Neu) in 10\^9/L; Lymphocyte count (Lym) in 10\^9/L; Monocyte count (Mon) in 10\^9/L; Eosinophil count (Eos) in 10\^9/L; Basophil count(Bas) in 10\^9/L; Red blood cell count (RBC) in 10\^9/L; Platelets(PLT) in 10\^9/L; Hemoglobin (HGB) in g/L; Mean corpuscular hemoglobin concentration (MCHC) in g/L; Hematocrit (HCT) in percentage(%); Mean corpuscular volume (MCV) in femtoliter(fL).
Concentration of Lung tumor markers	The 4th, 12th, 24th week after administration	Cytokeratin 19 fragment (CYFRA21-1) in ng/mL; Neuron specific enolase (NSE) in ng/mL; Squamous cell carcinoma antigen (SCC) in ng/mL; Carcinoembryonic antigen (CEA) in ng/mL; Carbohydrate antigen(CA125) in Unit/mL.
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]：body temperature	The 4th, 12th, 24th week after administration	Body temperature in centigrade(℃)
Blood gas analysis	The 4th, 12th, 24th week after administration	PH; Arterial partial pressure of oxygen (PaO2) in mmHg Arterial partial pressure of carbon dioxide (PaCO2) in mmHg
Electrocardiogram	The 4th, 12th, 24th week after administration	Heart rate in beats/minute; PR interval in millisecond(ms) QRS interval in millisecond(ms) QT interval (uncorrected) in millisecond(ms)
Blood biochemistry	The 4th, 12th, 24th week after administration	Total protein (TP) in g/L; Albumin (ALB) in g/L; Total bilirubin (TBIL) in umol/L, Direct bilirubin (DBIL) in umol/L, Total bile acid (TBA) in umol/L, Creatinine (Cr) in umol/L, Uric acid (UriC) in umol/L; Alanine aminotransferase (ALT) in U/L Aspartate aminotransferase (AST) in U/L; Alkaline phosphatase (ALP) in U/L; Gamma glutamyl transpeptidase (GGT) in U/L; Lactate dehydrogenase (LDH) in U/L; Fasting blood glucose (Glu) in mmol/L; Potassium ions (K+) in mmol/L; Sodium ions (Na+) in mmol/L; Chloride ions (Cl -) in mmol/L; Calcium ions (Ca2+) in mmol/L; Glycated hemoglobin (HbA1c) in percentage(%);