A First-in-Human Study of XSTEM-OA in Patients With Knee Osteoarthritis

Study Overview
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Brief Summary
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The aim of the study is to assess safety, tolerability and preliminary efficacy of XSTEM-OA when administered as a single intra-articular injection to patients with symptomatic knee osteoarthritis. The study is divided into two parts; a dose escalation (Part A) and a dose expansion part (Part: B). Three dose levels are planned to be evaluated in Part A and selected dose level(s) will be further expanded in Part B.

Official Title
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A First-in-Human Open-Label Phase 1/2a Study to Evaluate Safety, Tolerability and Efficacy of a Single Intra-Articular Injection of Allogeneic Mesenchymal Stem Cells Selected for Integrin α10β1 (XSTEM-OA) in Adult Patients With Symptomatic Knee Osteoarthritis

Conditions
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Osteoarthritis, Knee

Intervention / Treatment
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* Biological: XSTEM-OA


Participation Criteria
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Eligibility Criteria
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Major inclusion criteria: Aged ≥40 and ≤75 years at Screening Radiological evidence of predominantly medial osteoarthritis in the knee, uni- or bilateral, of KL grade II to III Moderate to severe pain associated with osteoarthritis in the knee as measured by a VAS pain score of ≥35 and ≤90 mm Major exclusion criteria: Body mass index (BMI) of ≥35 at Screening Ongoing signs or symptoms of systemic or local infection Known knee infection in the study knee within 6 months of Screening History of clinically relevant concomitant joint disease, clinically-relevant knee deformities, or any clinically significant medical history of the ligament, or realignment surgery or joint replacement surgery Medical history of any autoimmune disease History of surgery in the study knee that occured within 6 months of Screening Treatment with immunosuppressive therapy (systemic or local) or any medication affecting the bone or cartilage metabolism within 6 months of Screening Patients who are immunocompromised as caused by a disease

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 75 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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: XSTEM-OA<br>Single intra-articular injection of XSTEM-OA | Biological: XSTEM-OA<br>* XSTEM-OA is an allogeneic, adipose tissue-derived, integrin alpha10beta1-selected and expanded mesenchymal stem cell (MSC) product for the treatment of osteoarthritis.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability: Adverse events (AEs) | Incidence, nature and severity of treatment-related AEs assessed by the Common Terminology Criteria for Adverse Events (CTCAE) | From start of study until 18 months after injection | 
| Safety and tolerability: 12-lead electrocardiogram (ECG) | Change in 12-lead electrocardiograms (ECGs) compared to baseline. | From start of study until 18 months after injection | 
| Safety and tolerability: Laboratory examinations | Changes in laboratory tests compared to baseline. The clinical laboratory tests include haematology, chemistry, coagulation and urinalysis. | From start of study until 18 months after injection | 
| Safety and tolerability: Physical examinations | Changes in physical examination compared to baseline. | From start of study until 18 months after injection | 
| Safety and tolerability: Vital signs | Changes in vital signs compared to baseline. Vital signs include blood pressure, pulse rate, respiratory rate and oral body temperature. | From start of study until 18 months after injection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Preliminary efficacy: Changes in Visual Analogue Scale (VAS) for pain compared to baseline |  | From start of study until 18 months after injection | 
| Preliminary efficacy: Changes in Knee injury and Osteoarthritis Outcome Score (KOOS) compared to baseline |  | From start of study until 18 months after injection | 
| Preliminary efficacy: Change in EuroQoL 5 Dimension 5 Level test (EQ-5D-5L) compared to baseline |  | From start of study until 18 months after injection | 
| Preliminary efficacy: Change in 40 m fast paced walk test compared to baseline |  | From start of study until 18 months after injection | 
| Preliminary efficacy: Change in cartilage structure compared to baseline, based on MRI assessment of cartilage volume and composition |  | From start of study until 18 months after injection | 
| Preliminary efficacy: Change in whole knee health compared to baseline, based on MRI assessment by the MRI Osteoarthritis Knee Score (MOAKS) |  | From start of study until 18 months after injection | 
| Preliminary efficacy: Change in inflammatory activity compared to baseline, based on MRI assessment of synovial thickness and synovial blood flow |  | From start of study until 18 months after injection | 
| Preliminary efficacy: Changes in joint space narrowing based on x-ray compared to baseline |  | From start of study until 18 months after injection |