A Study to Investigate the Safety and Effectiveness of Different Doses of Sprifermin in Participants With Osteoarthritis of the Knee (FORWARD)

Merck KGaA (EMD Serono)

Status and phase: Completed; Phase 2

Conditions: Osteoarthritis, Knee

Treatments: Drug: Sprifermin; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT01919164

EMR700692_006

2011-003059-20 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 549 patients

Sex: All

Ages: 40 to 85 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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549 participants in 5 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo

Sprifermin (AS902330) 30 mcg/placebo - 2 Cycles

Experimental group

Description:

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.

Treatment:

Drug: Sprifermin

Drug: Placebo

Sprifermin (AS902330) 30 mcg- 4 Cycles

Experimental group

Description:

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.

Treatment:

Drug: Sprifermin

Sprifermin (AS902330) 100 mcg/Placebo (2 cycles)

Experimental group

Description:

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.

Treatment:

Drug: Sprifermin

Drug: Placebo

Sprifermin (AS902330) 100 mcg- 4 Cycles

Placebo Comparator group

Description:

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.

Treatment:

Drug: Sprifermin