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

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

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.

Study Overview

• Status: Completed
• Conditions: Moderate to Severe Osteoarthritis
• Intervention / Treatment: Drug: Placebo; Drug: SM04690, 0.03mg/2mL; Drug: SM04690, 0.07mg/2mL; Drug: SM04690, 0.23mg/2mL

• Study Type: Interventional
• Enrollment (Actual): 61
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States
  • California
    • El Cajon, California, United States
    • Walnut Creek, California, United States
  • Florida
    • Miami, Florida, United States
  • Massachusetts
    • Boston, Massachusetts, United States
  • Pennsylvania
    • Duncansville, Pennsylvania, United States
  • Texas
    • Dallas, Texas, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Biosplice Therapeutics, Inc.

Publications and helpful links

General Publications

• Yazici Y, McAlindon TE, Fleischmann R, Gibofsky A, Lane NE, Kivitz AJ, Skrepnik N, Armas E, Swearingen CJ, DiFrancesco A, Tambiah JRS, Hood J, Hochberg MC. A novel Wnt pathway inhibitor, SM04690, for the treatment of moderate to severe osteoarthritis of the knee: results of a 24-week, randomized, controlled, phase 1 study. Osteoarthritis Cartilage. 2017 Oct;25(10):1598-1606. doi: 10.1016/j.joca.2017.07.006. Epub 2017 Jul 13.

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (Actual): September 1, 2015
• Study Completion (Actual): September 1, 2015

Study Registration Dates

• First Submitted: March 18, 2014
• First Submitted That Met QC Criteria: March 24, 2014
• First Posted (Estimate): March 26, 2014

Study Record Updates

• Last Update Posted (Estimate): December 10, 2015
• Last Update Submitted That Met QC Criteria: December 8, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Anti-Inflammatory Agents; Lorecivivint
• Other Study ID Numbers: SM04690-01