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

Phase 1

Completed

• Conditions: Moderate to Severe Osteoarthritis
• Interventions: Drug: SM04690, 0.23mg/2mL; Drug: SM04690, 0.03mg/2mL; Drug: SM04690, 0.07mg/2mL; Drug: Placebo

• Registration Number: NCT02095548
• Lead Sponsor: Biosplice Therapeutics, Inc.

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2014-03
• Study First Submitted: 2014-03-18
• Study First Submitted QC: 2014-03-24
• Study First Posted: 2014-03-26
• Primary Completion: 2015-09
• Study Completion: 2015-09
• Status Verified: 2015-12
• Last Update Submitted: 2015-12-08
• Last Update Posted: 2015-12-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 61

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
SM04690, 0.23mg/2mL	SM04690, 0.23mg/2mL	Single, intra-articular injection of SM04690, 0.23mg/2mL
SM04690, 0.03mg/2mL	SM04690, 0.03mg/2mL	Single, intra-articular injection of SM04690, 0.03mg/2mL
SM04690, 0.07mg/2mL	SM04690, 0.07mg/2mL	Single, intra-articular injection of SM04690, 0.07mg/2mL
Placebo	Placebo	Single, intra-articular injection of placebo

Primary Outcome Measures

Name	Time	Method
The following PK parameters will be determined from the plasma of SM04690; Cmax, Tmax, AUC0-t, AUC0-∞, and t1/2	during 12 weeks
Additional safety assessment of bone loss as measured by CT of the knee	during 24 weeks
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

Secondary Outcome Measures

Name	Time	Method
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
Change from baseline per physician global assessment of disease scale	during 24 weeks
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 in joint space width as measured by X-ray	during 24 weeks