Clinical trial NCT02095548: Phase 1, Dose Escalation Study Evaluating the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of SM04690 in Moderate to Severe Knee Osteoarthritis (OA)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Moderate to Severe Osteoarthritis
Lead sponsor: Biosplice Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2014-03-26
Enrollment: 61
Sex: ALL
Minimum age (years): 50
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Safety assessments for this study will include adverse events, dose limiting toxicity (DLT), physical exams, vital signs, ECGs, and clinical laboratory tests
timeFrame: during 24 weeks
measure: Additional safety assessment of bone loss as measured by CT of the knee
timeFrame: during 24 weeks
measure: The following PK parameters will be determined from the plasma of SM04690; Cmax, Tmax, AUC0-t, AUC0-∞, and t1/2
timeFrame: during 12 weeks
Secondary outcomes:
measure: Change from baseline pain over the last 48 hours using a Visual Analog Scale (VAS)
timeFrame: during 24 weeks
measure: Change from baseline per Western Ontario and McMaster Osteoarthritis (WOMAC) assessment of disease scale
timeFrame: During 24 weeks
measure: Change from baseline per physician global assessment of disease scale
timeFrame: during 24 weeks
measure: Change from baseline in joint space width as measured by X-ray
timeFrame: during 24 weeks
measure: Change from baseline of cartilage volume and thickness as measure by MRI
timeFrame: during 24 weeks
measure: Change from baseline of biomarkers of cartilage synthesis and cytokines
timeFrame: during 24 weeks
Other outcomes:
Locations:
city: Tucson
country: United States
state: Arizona
city: El Cajon
country: United States
state: California
city: Walnut Creek
country: United States
state: California
city: Miami
country: United States
state: Florida
city: Boston
country: United States
state: Massachusetts
city: Duncansville
country: United States
state: Pennsylvania
city: Dallas
country: United States
state: Texas
Study officials:
References:
citation: 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.