Phase 1, Dose Escalation Study Evaluating the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of SM04690 in Moderate to Severe Knee Osteoarthritis (OA)

Study Overview
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Brief Summary
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The purpose of this study is to find the optimal dose of SM04690 that can be safely given by intra-articular injection into the target knee joint of subjects with moderate to severe osteoarthritis.

Official Title
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A Phase 1, Placebo-Controlled, Double-Blind, Dose-Escalation Study Evaluating the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of SM04690 Injected in the Target Knee Joint of Moderately to Severely Symptomatic Osteoarthritis Subjects

Conditions
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Moderate to Severe Osteoarthritis

Intervention / Treatment
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* Drug: SM04690, 0.03mg/2mL
* Drug: SM04690, 0.07mg/2mL
* Drug: SM04690, 0.23mg/2mL
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with primary OA in target knee by American College of Rheumatology (ACR) criteria Screening pain criteria sufficient as assessed by WOMAC and VAS scores Ability to read and understand the informed consent Exclusion Criteria: Women who are pregnant or lactating or child bearing potential, men must use a barrier method of contraception Any condition, including laboratory findings, that in the opinion of the investigator constitutes a risk or contraindication for participation in the study or that could interfere with the study objectives, conduct or evaluation Body mass index >40 Major knee surgery in the target knee within 12 months prior to study or planned surgery during the study period History of malignancy within the last 5 years Participation in a clinical research trial within 12 weeks prior Treatment of the target knee with intra-articular steroids within 2 months or hyaluronic acid derivatives within 6 months Effusion of the target knee requiring aspiration within 3 months Use of electrotherapy or acupuncture for OA within 4 weeks Significant and clinically evident misalignment of the target knee Any known active infections Any chronic condition that has not been well controlled for a minimum of 3 months

Ages Eligible for Study
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Minimum Age: 50 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SM04690, 0.03mg/2mL<br>Single, intra-articular injection of SM04690, 0.03mg/2mL | Drug: SM04690, 0.03mg/2mL<br> <br> |
| Experimental: SM04690, 0.07mg/2mL<br>Single, intra-articular injection of SM04690, 0.07mg/2mL | Drug: SM04690, 0.07mg/2mL<br> <br> |
| Experimental: SM04690, 0.23mg/2mL<br>Single, intra-articular injection of SM04690, 0.23mg/2mL | Drug: SM04690, 0.23mg/2mL<br> <br> |
| Placebo Comparator: Placebo<br>Single, intra-articular injection of placebo | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety assessments for this study will include adverse events, dose limiting toxicity (DLT), physical exams, vital signs, ECGs, and clinical laboratory tests |  | during 24 weeks | 
| Additional safety assessment of bone loss as measured by CT of the knee |  | during 24 weeks | 
| The following PK parameters will be determined from the plasma of SM04690; Cmax, Tmax, AUC0-t, AUC0-∞, and t1/2 |  | during 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline pain over the last 48 hours using a Visual Analog Scale (VAS) |  | during 24 weeks | 
| Change from baseline per Western Ontario and McMaster Osteoarthritis (WOMAC) assessment of disease scale |  | During 24 weeks | 
| Change from baseline per physician global assessment of disease scale |  | during 24 weeks | 
| Change from baseline in joint space width as measured by X-ray |  | during 24 weeks | 
| Change from baseline of cartilage volume and thickness as measure by MRI |  | during 24 weeks | 
| Change from baseline of biomarkers of cartilage synthesis and cytokines |  | during 24 weeks |