A Study of NCR100 Injection for the Treatment of Knee Osteoarthritis（ KOA）

A Study to Evaluate the Safety, Tolerability and Efficacy of NCR100 Injection for the Treatment of Knee Osteoarthritis（ KOA）

This clinical study is to investigate the safety and efficacy of NCR100 injection in subjects with knee osteoarthritis (KOA). It contains two parts dose-escalating, and blind random study in adult KOA subjects.

Study Overview

• Status: Not yet recruiting
• Conditions: Knee Osteoarthritis
• Intervention / Treatment: Biological: NCR100; Other: 0.9% Normal saline

Detailed Description

Knee osteoarthritis(KOA) is a kind of degenerative joint disease characterized by chronic inflammation loss of articular cartilage and subchondral bone remodeling.In China, the estimated number of patients diagnosed with KOA reached 37.35millon. The aim of this sudy 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.

• Study Type: Interventional
• Enrollment (Estimated): 162
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Yanqiu Li, PHD; Phone Number: 021-64369181; Email: yqli@nuwacell.com
• Study Contact Backup: Name: Changqing 021-64369181, PHD; Phone Number: 021-64369181

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Subjects who understand and voluntarily sign the Informed Consent Form（ICF） before the enrolment;
• Age: 40-65 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
• Kellgren-Lawrence grade: II-III

Exclusion Criteria:

• Subjects previously diagnosed of secondary knee osteoarthritis, or those diagnosed with hip/ankle joint disease requiring medical intervention;
• Suffering from other diseases that impair knee function or joints;
• Have received stem cell therapy;
• Have knee injury history;
• Experienced knee surgery, or plan to undergo knee surgery;
• Received analgesics to relieve pain before Investigational Medicinal Product(IMP) injections;
• Have used traditional Chinese medicine to treat KOA within 4 weeks;
• Have used intra-articular injection of drugs to treat KOA within 12 weeks;
• Received glucosamine,chondroitin sulfate, or diacetate therapy before investigational drug intervention within 12 weeks;
• Subjects with acute phase of knee osteoarthritis;
• Severe deformity of the knee;
• Known or suspected allergy or a history of allergies;
• Abnormal results of laboratory examination as follows: Hepatic Insufficiency （Alanine Aminotransferase>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≥30kg/m^2
• Severe systemic infection or local knee joint infection;
• Have received systemic glucocorticoid therapy before intervention or need to take systemic glucocorticoid therapy during the treatment;
• Have a history of acute myocardial infarction or severe heart diseases,QT prolongation;
• Subjects with peripheral or central nervous system disorders that may interfere assessments;
• Have contraindications to Magnetic Resonance Imaging(MRI)
• Subjects who are unable to walk on his own;
• Subjects with alcohol/drug addiction/abuse or mental disorders;
• Pregnant or lactating, or unable to comply with contraceptives within 6 months after end of study;
• Have participated in other clinical trials within 12 weeks before the screening;
• Severe and poorly controlled comorbidities;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NCR100 injection; Subjects will receive four injections of NCR100	Biological: NCR100; Subjects will receive multiple intra-articular NCR100 injections.
Placebo Comparator: 0.9% Normal saline; Subjects will receive four injections of 0.9% Normal saline	Other: 0.9% Normal saline; Subjects will receive multiple intra-articular 0.9% Normal saline injections.
Experimental: NCR100 injection and 0.9% Normal saline; Subjects will receive two injections of 0.9% Normal saline and two injections of NCR100	Biological: NCR100; Subjects will receive multiple intra-articular NCR100 injections.; Other: 0.9% Normal saline; Subjects will receive multiple intra-articular 0.9% Normal saline injections.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose-Limiting Toxicity(DLT)	Number of participants with Dose-limiting toxicity in 28 days	4 weeks after first injection
The Western Ontario and McMaster Universities osteoarthritis index(WOMAC)	Differences of WOMAC scores in changes from baseline between the experimental group and the control group	48 weeks after first injection

Secondary 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 assessed by CTCAE v5.0	Within 48 weeks of the first infusion
Visual analogue scale (VAS)	Differences in changes from baseline between experimental groups and the control group.	8 weeks, 12 weeks, 24 weeks, 36 weeks and 48 weeks
Differences in changes from baseline at 8 weeks, 12 weeks, 24 weeks and 36 weeks of the Western Ontario and McMaster Universities Arthritis Index (WOMAC) between the experimental groups and the control group	WOMAC scores include three subscale scores (pain, stiffness, and physical function)	8 weeks, 12 weeks, 24 weeks and 36 weeks
Differences in changes from baseline to 24 weeks and 48 weeks in cartilages with various regions	Magnetic resonance imaging (MRI) is used to scan images of knees.	24 weeks and 48 weeks

Collaborators and Investigators

• Sponsor: Nuwacell Biotechnologies Co., Ltd.
• Collaborators: Shanghai 6th People's Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): February 20, 2025
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): November 15, 2028

Study Registration Dates

• First Submitted: December 16, 2024
• First Submitted That Met QC Criteria: December 16, 2024
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 16, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: KOA; Mesenchymal Stromal Cells
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Arthritis; Joint Diseases; Rheumatic Diseases; Osteoarthritis; Osteoarthritis, Knee
• Other Study ID Numbers: NCR100-1002

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