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

A Phase 2, Randomized, Double-Blind, Vehicle-Controlled Study Evaluating the Safety, Efficacy and Pharmacokinetics of Single Dose EP-104IAR for 24 Weeks in Patients With Osteoarthritis of the Knee

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

Study Overview

• Status: Completed
• Conditions: Osteoarthritis, Knee
• Intervention / Treatment: Drug: EP-104IAR 25 mg; Drug: Vehicle

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.

• Study Type: Interventional
• Enrollment (Actual): 318
• Phase: Phase 2

Contacts and Locations

Study Locations

• Czechia
  • Brno, Czechia
    • CCR Brno, s.r.o
  • Pardubice, Czechia
    • CCR Czech a.s
  • Prague, Czechia
    • CCR Prague, s.r.o
• Denmark
  • Frederiksberg, Denmark
    • The Parker Institute, Frederiksberg Hospital
  • Gandrup, Denmark
    • Sanos Clinic Nordjylland
  • Herlev, Denmark
    • Sanos Clinic Herlev
  • Vejle, Denmark
    • Sanos Clinic Syddanmark
• Poland
  • Bytom, Poland
    • NZOZ BIF-MED s.c
  • Poznań, Poland
    • Medyczne Centrum Hetmańska
  • Warsaw, Poland
    • SOMED CR
  • Łódź, Poland
    • SOMED CR
  • Świdnica, Poland
    • DC-MED

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key 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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: EP-104IAR 25 mg; A single use intra-articular injection containing 25 mg of EP-104IAR	Drug: EP-104IAR 25 mg; Single 5 mL intra-articular injection
Placebo Comparator: Placebo (vehicle); A single use intra-articular injection containing no active ingredients	Drug: Vehicle; Single 5 mL intra-articular injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in Change From Baseline Between EP-104IAR and Vehicle in WOMAC Pain Subscale	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.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in Change From Baseline Between EP-104IAR and Vehicle in WOMAC Function Subscale	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.	12 weeks
Difference Between EP-104IAR and Vehicle in the Area Under the Curve (AUC) of WOMAC Pain Subscale	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.	12 weeks
Difference in Change From Baseline Between EP-104IAR and Vehicle in WOMAC Pain Subscale	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.	24 weeks
Difference Between EP-104IAR and Vehicle in OMERACT-OARSI Strict Responders	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.	12 weeks

Collaborators and Investigators

• Sponsor: Eupraxia Pharmaceuticals Inc.
• Collaborators: NBCD A/S
• Investigators: Study Director: Amanda Malone, Eupraxia Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): September 10, 2021
• Primary Completion (Actual): May 17, 2023
• Study Completion (Actual): June 1, 2023

Study Registration Dates

• First Submitted: October 7, 2019
• First Submitted That Met QC Criteria: October 7, 2019
• First Posted (Actual): October 9, 2019

Study Record Updates

• Last Update Posted (Actual): June 25, 2024
• Last Update Submitted That Met QC Criteria: May 29, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee
• Other Study ID Numbers: EP-104IAR-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No