Study to Evaluate the Efficacy and Safety of EP-104IAR in Patients With Osteoarthritis of the Knee

Phase 2

Completed

Conditions: Osteoarthritis, Knee

Interventions: Drug: EP-104IAR 25 mg
Drug: Vehicle

Registration Number: NCT04120402

Lead Sponsor: Eupraxia Pharmaceuticals Inc.

Brief Summary: The purpose of this study is to evaluate the safety, efficacy and pharmacokinetics (PK) of EP-104IAR in patients with osteoarthritis (OA) of the knee

Detailed Description: This is a randomized, double-blind, placebo-controlled, single injection, 24-week study to evaluate the safety, efficacy and PK of EP-104IAR in subjects with osteoarthritis knee pain

Following screening and baseline assessments to determine eligibility, each participant will receive a single IA injection of either EP-104IAR or placebo (vehicle). Participants will be followed up for 24 weeks following the injection for safety, PK and efficacy assessments.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 318

Inclusion Criteria

Males or females, aged ≥40 years
Body Mass Index (BMI) ≤ 40.0 kg/m2
Diagnosis of primary OA of the Index knee, with symptoms present for at least 6 months
OA severity Grade 2 or 3 (based on Kellgren Lawrence Grading Scale)
Unsatisfactory pain relief from at least 2 prior standard OA treatments
Qualifying pain in the Index knee during the baseline period
Ambulatory (without the need for a cane/other walking aide)
Female subjects willing to use highly effective birth control methods to prevent pregnancy
Willing and able to comply with study procedures and restrictions, including abstaining from use of restricted medications.

Key

Exclusion Criteria

OA of the Index knee due to acute injury or trauma, or unstable joint
X-ray evidence of chondrocalcinosis
Diagnosed or suspected ipsilateral hip OA
Knee pain that is not attributable to OA of the knee
Any other disorders that impact mobility, strength or sensation, or are a co-existent source of pain or inflammation that interfere with assessment of knee pain and function
History of infection in the Index knee
Skin breakdown on the Index knee where the injection will take place
Total Knee Replacement, or any other surgery (including arthroscopy) for the Index knee within prior 12 months, or planned surgery during the study
Total Knee Replacement Surgery of the non-Index knee within prior 6 months, or planned surgery (any location) during the study that would require a restricted medication
IA injection of corticosteroids in any joint within prior 3 months or IA injection of extended-release corticosteroids in any joint within prior 6 months
IA injection in the Index knee of platelet rich plasma, or other prolotherapy within prior 3 months, or hyaluronic acid within prior 6 months
Recent, current or planned use of corticosteroids for any indication (except for permitted uses)
Recent, current or planned use of prohibited medications (including analgesics, marijuana, investigational drugs and devices, immunosuppressive therapy), or unwilling or unable to stop using prohibited medications during the study.
Conditions including: sarcoidosis, amyloidosis, osteomyelitis, Cushing's Syndrome, hepatic or renal disease, Psychotic disorder, bipolar disorder, symptomatic depressive or anxiety disorders.
Current malignancy of any type, or history of a malignancy within prior 12 months
Active or quiescent systemic fungal, bacterial (including tuberculosis) viral (including HIV, Hepatitis B or C) or parasitic infections, or ocular herpes simplex, or any recent infection requiring IV or oral antibiotics
Laboratory results indicative of adrenal insufficiency, diabetes or renal or hepatic disease.
Positive urine drug screen for a substance of abuse
Females who are pregnant, lactating
Known or suspected hypersensitivity or contraindication to ingredients in the study drug

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
EP-104IAR 25 mg	EP-104IAR 25 mg	A single use intra-articular injection containing 25 mg of EP-104IAR
Placebo (vehicle)	Vehicle	A single use intra-articular injection containing no active ingredients

Primary Outcome Measures

Name	Time	Method
Difference in Change From Baseline Between EP-104IAR and Vehicle in WOMAC Pain Subscale	12 weeks	Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale (scores scaled 0-10, with 10 being the worst). Least squares mean from a mixed model for repeated measures (MMRM) for change from baseline with fixed effects for site, treatment, week, treatment-by-week interaction; random effect for subject; and covariate baseline WOMAC pain score.

Secondary Outcome Measures

Name	Time	Method
Difference in Change From Baseline Between EP-104IAR and Vehicle in WOMAC Function Subscale	12 weeks	Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) function subscale (scores scaled 0-10, with 10 being the worst). Function subscale includes questions related to the physical functioning of osteoarthritis e.g. stair use, standing, walking etc. From a mixed model for repeated measures (MMRM) for change from baseline with fixed effects for site, treatment, week, treatment-by-week interaction; random effect for subject; and covariate baseline WOMAC function score.
Difference Between EP-104IAR and Vehicle in the Area Under the Curve (AUC) of WOMAC Pain Subscale	12 weeks	Area under the curve in change from baseline Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale (scores scaled 0-10, with 10 being the worst) from Week 0 to Week 12 was calculated on a per-individual basis using the linear trapezoidal rule. AUC was normalized to account for subjects whose actual days and nominal days at Week 12 differed. Treatments were compared using an ANCOVA model containing site; individual baseline WOMAC Pain; and treatment group as covariates.
Difference in Change From Baseline Between EP-104IAR and Vehicle in WOMAC Pain Subscale	24 weeks	Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale (scores scaled 0-10, with 10 being the worst). Least squares mean from a mixed model for repeated measures (MMRM) for change from baseline with fixed effects for site, treatment, week, treatment-by-week interaction; random effect for subject; and covariate baseline WOMAC pain score.
Difference Between EP-104IAR and Vehicle in OMERACT-OARSI Strict Responders	12 weeks	Outcome Measures in Rheumatology-Osteoarthritis Research Society International (OMERACT-OARSI) strict responders are defined as at least 50% improvement (decrease from baseline) in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain or function subscales (scores scaled 0-10, with 10 being the worst) and an absolute change of at least 2 in the respective score. Patients who discontinued prior to Week 12 were considered non-responders.

Trial Locations

Locations (11): The Parker Institute, Frederiksberg Hospital
🇩🇰
Frederiksberg, Denmark
CCR Czech a.s
🇨🇿
Pardubice, Czechia
CCR Brno, s.r.o
🇨🇿
Brno, Czechia
CCR Prague, s.r.o
🇨🇿
Prague, Czechia
Sanos Clinic Nordjylland
🇩🇰
Gandrup, Denmark
Sanos Clinic Herlev
🇩🇰
Herlev, Denmark
Sanos Clinic Syddanmark
🇩🇰
Vejle, Denmark
NZOZ BIF-MED s.c
🇵🇱
Bytom, Poland
Somed CR
🇵🇱
Łódź, Poland
DC-MED
🇵🇱
Świdnica, Poland
Medyczne Centrum Hetmańska
🇵🇱
Poznań, Poland