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

NCT01919164 | Completed Phase 2 Results DMC

• 2 other identifiers: EMR700692_0062011-003059-20
• Study Type: interventional
• Target: 549
• Locations: 8 countries
• Sites: 13

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.

Conditions

Osteoarthritis, Knee

Keywords

Osteoarthritis of knee; Recombinant Human Fibroblast Growth Factor-18 (rhFGF-18); Sprifermin; Placebo

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Cartilage Thickness in the Total Femorotibial Joint as Evaluated by Quantitative Magnetic Resonance Imaging (qMRI) at Year 2

  The change in cartilage thickness at 2 years was calculated based on quantitative magnetic resonance imaging (qMRI).

  Baseline, Year 2 (Week 104)

Secondary Outcomes (8)

• 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 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 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 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

• 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

Study Arms (5)

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Sprifermin (AS902330) 30 mcg/placebo - 2 Cycles

EXPERIMENTAL

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.

Drug: Sprifermin; Drug: Placebo

Sprifermin (AS902330) 30 mcg- 4 Cycles

EXPERIMENTAL

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.

Drug: Sprifermin

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

EXPERIMENTAL

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.

Drug: Sprifermin; Drug: Placebo

Sprifermin (AS902330) 100 mcg- 4 Cycles

PLACEBO COMPARATOR

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.

Drug: Sprifermin

Interventions

Sprifermin DRUG

Participants received Sprifermin as intra-articular injection.

Also known as: Recombinant Human Fibroblast Growth Factor-18 (rhFGF-18)

Sprifermin (AS902330) 100 mcg- 4 Cycles; Sprifermin (AS902330) 100 mcg/Placebo (2 cycles); Sprifermin (AS902330) 30 mcg- 4 Cycles; Sprifermin (AS902330) 30 mcg/placebo - 2 Cycles

Placebo DRUG

Participants received Placebo matched to sprifermin as intra-articular injection.

Placebo; Sprifermin (AS902330) 100 mcg/Placebo (2 cycles); Sprifermin (AS902330) 30 mcg/placebo - 2 Cycles

Eligibility Criteria

• Age: 40 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• EMD Serono Research & Development Institute, Inc.: lead
• Nordic Bioscience A/S: collaborator

Study Sites (13)

Research site

Lakewood, Colorado, United States

Location

Research site

Baltimore, Maryland, 21201, United States

Location

Research site

Buenos Aires, Argentina

Location

Research site

Brno, Czechia

Location

Research site

Pardubice, Czechia

Location

Research site

Prague, Czechia

Location

Research site

Aalborg, Denmark

Location

Research site

Ballerup Municipality, Denmark

Location

Research site

Vejle, Denmark

Location

Research site

Tallinn, Estonia

Location

Research Site

Hong Kong, Hong Kong

Location

Research site

Lodz, Poland

Location

Research site

Bucharest, Romania

Location

Related Publications (6)

• Conaghan PG, Katz N, Hunter DJ, Guermazi A, Hochberg MC, Somberg K, Clive J, Knight C, Johnson M, Zhao L, Goel N. Exploring a novel outcome measure of symptom progression in knee osteoarthritis utilizing a large randomized trial. Osteoarthritis Cartilage. 2025 Mar;33(3):383-390. doi: 10.1016/j.joca.2024.12.003. Epub 2024 Dec 28.

  PMID: 39734047 DERIVED

• Eckstein F, Maschek S, Wirth W, Ladel C, Bihlet AR, Knight C, Somberg K, Zhao L. Unbiased analysis of knee cartilage thickness change over three years after sprifermin vs. placebo treatment - A post-hoc analysis from the phase 2B FORWARD study. Osteoarthr Cartil Open. 2024 Aug 23;6(4):100513. doi: 10.1016/j.ocarto.2024.100513. eCollection 2024 Dec.

  PMID: 39286575 DERIVED

• Eckstein F, Hochberg MC, Guehring H, Moreau F, Ona V, Bihlet AR, Byrjalsen I, Andersen JR, Daelken B, Guenther O, Ladel C, Michaelis M, Conaghan PG. Long-term structural and symptomatic effects of intra-articular sprifermin in patients with knee osteoarthritis: 5-year results from the FORWARD study. Ann Rheum Dis. 2021 Aug;80(8):1062-1069. doi: 10.1136/annrheumdis-2020-219181. Epub 2021 May 7.

  PMID: 33962962 DERIVED

• Guehring H, Moreau F, Daelken B, Ladel C, Guenther O, Bihlet AR, Wirth W, Eckstein F, Hochberg M, Conaghan PG. The effects of sprifermin on symptoms and structure in a subgroup at risk of progression in the FORWARD knee osteoarthritis trial. Semin Arthritis Rheum. 2021 Apr;51(2):450-456. doi: 10.1016/j.semarthrit.2021.03.005. Epub 2021 Mar 11.

  PMID: 33752164 DERIVED

• Eckstein F, Kraines JL, Aydemir A, Wirth W, Maschek S, Hochberg MC. Intra-articular sprifermin reduces cartilage loss in addition to increasing cartilage gain independent of location in the femorotibial joint: post-hoc analysis of a randomised, placebo-controlled phase II clinical trial. Ann Rheum Dis. 2020 Apr;79(4):525-528. doi: 10.1136/annrheumdis-2019-216453. Epub 2020 Feb 25.

  PMID: 32098758 DERIVED

• Hochberg MC, Guermazi A, Guehring H, Aydemir A, Wax S, Fleuranceau-Morel P, Reinstrup Bihlet A, Byrjalsen I, Ragnar Andersen J, Eckstein F. Effect of Intra-Articular Sprifermin vs Placebo on Femorotibial Joint Cartilage Thickness in Patients With Osteoarthritis: The FORWARD Randomized Clinical Trial. JAMA. 2019 Oct 8;322(14):1360-1370. doi: 10.1001/jama.2019.14735.

  PMID: 31593273 DERIVED

Related Links

• Trial Awareness and Transparency website Scope
• US Medical Information website, Medical Resources

MeSH Terms

Conditions

Osteoarthritis, Knee

Interventions

fibroblast growth factor 18

Condition Hierarchy (Ancestors)

Osteoarthritis; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Results Point of Contact

• Title: Communication Center
• Organization: Merck KGaA, Darmstadt, Germany

service@emdgroup.com

+49-6151-72-5200

Study Officials

• Medical Responsible, MD

  Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 7, 2013
• First Posted: August 8, 2013
• Study Start: July 29, 2013
• Primary Completion: May 5, 2016
• Study Completion: May 7, 2019
• Last Updated: July 13, 2020
• Results First Posted: July 13, 2020

Record last verified: 2020-06

Locations

HK (1); DK (3); US (2); AR (1); ES (1); PL (1); CZ (3); RO (1)