A Multicenter, Randomized, Double-blind, Placebo Controlled, Parallel-group Trial to Investigate the Efficacy and Safety of Different Intra Articular (i.a.) Dosages of Sprifermin in Subjects With Primary Osteoarthritis of the Knee
Overview
- Phase
- Phase 2
- Intervention
- Placebo
- Conditions
- Osteoarthritis, Knee
- Sponsor
- EMD Serono Research & Development Institute, Inc.
- Enrollment
- 549
- Locations
- 2
- Primary Endpoint
- Change From Baseline in Cartilage Thickness in the Total Femorotibial Joint as Evaluated by Quantitative Magnetic Resonance Imaging (qMRI) at Year 2
- Status
- Completed
- Last Updated
- 5 years ago
Overview
Brief Summary
This was a multicenter, randomized, double-blind, placebo-controlled, parallel-group Phase 2 trial of Sprifermin administered intra-articularly in participants with primary osteoarthritis of the knee and Kellgren-Lawrence Grade 2 or 3. The trial was intended to investigate the efficacy and safety of different intra articular dosages of Sprifermin in these individuals.
Detailed Description
Participants were equally randomized to either one of 4 treatment arms or a placebo arm. The trial consists of a Screening period lasting up to 42 days, a two-year double-blind placebo-controlled (DBPC) treatment phase, which begins at randomization (Week 0) and ends at Year 2, and a 3-year extended follow-up phase.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Age from 40 to 85 years; of either sex
- •Primary femorotibial osteoarthritis according to American College of Rheumatology (ACR) clinical and radiographic criteria , and meeting protocol-specified X-ray criteria in the target knee at screening
- •Pain score in the target knee and/or the need for regular symptomatic treatment of knee pain with paracetamol (acetaminophen), systemic non-steroidal anti-inflammatory drugs (NSAIDs) including cyclooxygenase (COX)-2 selective inhibitors (coxibs), or tramadol on most days in the previous month (that is, more than half of the days in the previous month)
- •A history of pain due to Osteoarthritis in the target knee for at least 6 months
- •A protocol-specified pain score for the target knee in response to Question 1 of the WOMAC pain index ("how much pain have you had \[in the target knee, over the past 48 hours\] when walking on a flat surface?") after washout of at least 5 half-lives of analgesic medication(s): acetaminophen, topical or oral NSAIDS, coxibs, opioids, and/or tramadol
- •Women of childbearing potential must use a form of contraception with a failure rate of less than 1 percent per year throughout the trial
Exclusion Criteria
- •Malalignment of greater than 5 degrees in the femorotibial axis of the target knee
- •Clinical signs of inflammation (redness) in the target knee
- •Intra-articular administration of corticosteroids or hyaluronic acid into either knee within 6 months before Screening
- •Planned knee surgery (affecting either the target or the contralateral knee) within the next two years
- •Concomitant conditions or treatments deemed to be incompatible with trial participation
- •Any contraindication to MRI according to MRI guidelines, including the inability to undergo a knee MRI exam because of inability to fit in the scanner or knee coil
- •Pregnancy or breastfeeding
- •Participation in another clinical trial within the 30 days (or 5 half-lives of the investigated compound, whichever is longer) before screening
- •Legal incapacity or limited legal capacity
Arms & Interventions
Placebo
Participants received Placebo matched to Sprifermin as intra-articular injection once every week for 3 consecutive weeks for 4 cycles, that is at week 0, 1, 2 in Cycle 1; at week 26, 27, 28 in Cycle 2; at week 52, 53, 54 in Cycle 3 and at week 78, 79, 80 in Cycle 4 at interval of 6 months.
Intervention: Placebo
Sprifermin (AS902330) 30 mcg/placebo - 2 Cycles
Participants received Sprifermin 30 mcg as intra-articular injection once every week for 3 consecutive weeks for 2 alternative cycles, that is at week 0, 1, 2 in Cycle 1 and at week 52, 53, 54 in Cycle 3; and received placebo matched to Sprifermin once every week for 3 consecutive weeks for 2 alternative cycles, that is at week 26, 27, 28 in Cycle 2 and at week 78, 79, 80 in Cycle 4 at interval of 6 months.
Intervention: Sprifermin
Sprifermin (AS902330) 30 mcg/placebo - 2 Cycles
Participants received Sprifermin 30 mcg as intra-articular injection once every week for 3 consecutive weeks for 2 alternative cycles, that is at week 0, 1, 2 in Cycle 1 and at week 52, 53, 54 in Cycle 3; and received placebo matched to Sprifermin once every week for 3 consecutive weeks for 2 alternative cycles, that is at week 26, 27, 28 in Cycle 2 and at week 78, 79, 80 in Cycle 4 at interval of 6 months.
Intervention: Placebo
Sprifermin (AS902330) 30 mcg- 4 Cycles
Participants received Sprifermin 30 micrograms (mcg) as intra-articular injection once every week for 3 consecutive weeks for 4 cycles, that is at week 0, 1, 2 in Cycle 1; at week 26, 27, 28 in Cycle 2; at week 52, 53, 54 in Cycle 3 and at week 78, 79, 80 in Cycle 4 at interval of 6 months.
Intervention: Sprifermin
Sprifermin (AS902330) 100 mcg/Placebo (2 cycles)
Participants received Sprifermin 100 mcg as intra-articular injection once every week for 3 consecutive weeks for 2 alternative cycles, that is at week 0, 1, 2 in Cycle 1 and at week 52, 53, 54 in Cycle 3; and received placebo matched to Sprifermin once every week for 3 consecutive weeks for 2 alternative cycles, that is at week 26, 27, 28 in Cycle 2 and at week 78, 79, 80 in Cycle 4 at interval of 6 months.
Intervention: Sprifermin
Sprifermin (AS902330) 100 mcg/Placebo (2 cycles)
Participants received Sprifermin 100 mcg as intra-articular injection once every week for 3 consecutive weeks for 2 alternative cycles, that is at week 0, 1, 2 in Cycle 1 and at week 52, 53, 54 in Cycle 3; and received placebo matched to Sprifermin once every week for 3 consecutive weeks for 2 alternative cycles, that is at week 26, 27, 28 in Cycle 2 and at week 78, 79, 80 in Cycle 4 at interval of 6 months.
Intervention: Placebo
Sprifermin (AS902330) 100 mcg- 4 Cycles
Participants received Sprifermin 100 mcg as intra-articular injection once every week for 3 consecutive weeks for 4 cycles, that is at week 0, 1, 2 in Cycle 1; at week 26, 27, 28 in Cycle 2; at week 52, 53, 54 in Cycle 3 and at week 78, 79, 80 in Cycle 4 at interval of 6 months.
Intervention: Sprifermin
Outcomes
Primary Outcomes
Change From Baseline in Cartilage Thickness in the Total Femorotibial Joint as Evaluated by Quantitative Magnetic Resonance Imaging (qMRI) at Year 2
Time Frame: Baseline, Year 2 (Week 104)
The change in cartilage thickness at 2 years was calculated based on quantitative magnetic resonance imaging (qMRI).
Secondary Outcomes
- Change From Baseline in the 20-meter Walk Test at Week 12, 26, 38, 52, 64, 78, 90 and 104(Baseline, Week 12, 26, 38, 52, 64, 78, 90 and 104)
- Change From Baseline in Minimal Joint Space Width (mJSW) in the Medial and Lateral Compartments as Evaluated by X-ray at Week 52 and 104(Baseline, Week 52 and 104)
- Changes From Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale, Stiffness Subscale, Physical Function Subscale and Total Score at Week 52, Week 78 and Week 104(Baseline, Week 52, Week 78 and Week 104)
- Change From Baseline in Cartilage-Volume in the Medial and Lateral Compartments as Well as in the Total Femorotibial Joint at Week 26, 52, 78 and 104(Baseline, Week 26, 52, 78 and 104)
- Change From Baseline in the Patient's Global Assessment (PGA) at Week 12, 26, 38, 52, 64, 78, 90 and 104(Baseline, Week 12, 26, 38, 52, 64, 78, 90 and 104)
- Change From Baseline in Cartilage Thickness in the Medial and Lateral Compartments as Well as in the Total Femorotibial Joint(Medial and Lateral: Baseline, Week 26, 52, 78 and 104; Total: Baseline, Week 26, 52 and 78)
- Serum Levels of Sprifermin/FGF-18(Pre-dose at Week 0, 2 hours post-dose at Week 1 and 2 of Cycle 1, 2, 3 and 4 (each cycle is of 28 days))
- Synovial Fluid Levels of Sprifermin/FGF-18(Pre-dose at Week 0, 2 hours post-dose at Week 1 and 2 of Cycle 1, 2, 3 and 4 (each cycle is of 28 days))