A Trial to Evaluate the Safety, Tolerability, and Efficacy of NCR100 Injection in the Treatment of Subjects With KOA

Study Overview
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Brief Summary
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This clinical study is to investigate the safety and efficacy of NCR100 injection in subjects with knee osteoarthritis (KOA). It is a dose-escalating, open label study in adult KOA subjects.

Detailed Description
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Knee osteoarthritis (KOA) is a kind of degenerative joint disease and there are over 300 million cases worldwide. The aim of this clinical trial is to evaluate the safety, tolerability, and efficacy of human pluripotent stem cell derived mesenchymal stromal cells (NCR100) injection in the treatment of subjects with knee osteoarthritis.

Official Title
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A Phase I, Open Label, Single Arm, Multiple Center, Dose Escalation Clinical Trial to Evaluate the Safety, Tolerability and Efficacy of Human Induced Pluripotent Stem Cell Derived Mesenchymal Stromal Cells (NCR100) Injection in the Treatment of Subjects With Knee Osteoarthritis

Conditions
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Knee Osteoarthritis

Intervention / Treatment
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* Biological: NCR100 injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who understand and voluntarily sign the Informed Consent Form（ICF） before the enrolment; Age: 40-80 years old, both genders; Diagnosis of knee osteoarthritis based on American College of Rheumatology criteria; Subjects with KOA who have persistent pain for more than six months, or aggravation or recurrence of osteoarthritis after routine medication; Kellgren-Lawrence grade: II-III; McMaster Universities Osteoarthritis Index (WOMAC): 24-72. Exclusion Criteria: Subjects previously diagnosed of secondary knee osteoarthritis, or those diagnosed with hip/ankle joint disease requiring medical intervention; Subjects who suffering from other diseases that cause damage to knee joint function or affect joints; Subjects who have received allogeneic mesenchymal progenitor (stem/stromal) cell therapy; Subjects who have history of knee joint injury; Subjects who have undergone knee arthroscopic surgery; Subjects who received painkillers ( eg,opioids/nonsteroidal anti-inflammatory analgesics ) to treat knee osteoarthritis; Subjects who have orally taken traditional Chinese medicine; Subjects who have received intra-articular drug injection to treat knee osteoarthritis; Subjects with glucosamine, chondroitin sulfate, or diacetate therapy before investigational drug intervention Subjects with acute reactive knee osteoarthritis; Severe eversion deformity in target knee joint; Known or suspected allergy or a history of allergies; Subjects with abnormal results of laboratory examination: Hepatic Insufficiency (ALT > 2xULN or Aspartate aminotransferase（AST） > 2xULN), renal dysfunction (creatinine clearance rate ≤60ml/min or blood urea nitrogen(BUN) > 2× ULN), Coagulation Defects (INR > 1.5) or severe hematological diseases (Grade 3 or above anemia Hb < 8 g/dL, Grade 2 or above thrombocytopenia platelet count(PLT) < 75×10^9/L) ; BMI≥30 kg/m^2 ; Severe systemic infection or local knee joint infection; Subjects who have received systemic glucocorticoid therapy before intervention or need to take systemic glucocorticoid therapy during the treatment; Subjects who have history of acute myocardial infarction or with heart diseases e.g.uncontrolled angina pectoris, uncontrolled arrhythmias, severe heart failure (NYHA > III), QT prolongation, and are determined by investigators as not suitable to participate in this clinical trial; Subjects with peripheral or central nervous system disorders that may interfere with knee joint pain and functional assessment, Subjects who have contraindications to MRI; Subjects who have poor physical condition and are unable to walk autonomously; Subjects with alcohol or drug addiction or with a clear history of mental disorders or with a history of drug abuse or drug use of psychotropic substances; Subjects with infection with hepatitis B virus(HBV), hepatitis C virus(HCV), HIV, and treponema pallidum confirmed by laboratory tests; Pregnant or lactating female subjects, or subjects who are unable to comply with contraceptives from the study period to 6 months after the end of this study; Subjects who have participated in other clinical trials and have used other study products; Subjects with severe and poorly controlled comorbidities and not suitable for this clinical trial; Subjects who are not suitable for this clinical trial for other reasons.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NCR100 injection<br>Cohort1:Low dose NCR100 injection; Cohort2:Mid-low dose NCR100 injection; Cohort3:Mid-high dose NCR100 injection; Cohort4:High dose NCR100 injection. | Biological: NCR100 injection<br>* Subjects will receive a one-dose intra-articular NCR100 injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Event(AE) or Serious Adverse Event(SAE) | Number of participants with treatment-related adverse events or serious adverse events as assessed by CTCAE v5.0 | Week1,Week2,Week4 | 
| Dose-Limiting Toxicity(DLT) | Number of participants with Dose-limiting toxicity in 28 days after injection | 4 weeks after injection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum plasma concentration(Cmax) |  | 30minutes before administration,24hours,1week,2week,4week,8week,12week and 24week after administration | 
| Elimination half life of drug(T1/2) |  | 30minutes before administration,24hours,1week,2week,4week,8week,12week and 24week after administration | 
| Time after doing at which maximun plasma concentration is reached(Tmax) |  | 30minutes before administration,24hours,1week,2week,4week,8week,12week and 24week after administration | 
| Area under the plasma concentration-time curve(AUC) |  | 30minutes before administration,24hours,1week,2week,4week,8week,12week and 24week after administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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KOA, Mesenchymal Stromal Cells