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

NCT ID: NCT01919164

Last Updated: 2020-07-13

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

549 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-07-29

Study Completion Date

2019-05-07

Brief Summary

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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

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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.

Conditions

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Osteoarthritis, Knee

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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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.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

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

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.

Group Type EXPERIMENTAL

Sprifermin

Intervention Type DRUG

Participants received Sprifermin as intra-articular injection.

Placebo

Intervention Type DRUG

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

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.

Group Type EXPERIMENTAL

Sprifermin

Intervention Type DRUG

Participants received Sprifermin as intra-articular injection.

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.

Group Type EXPERIMENTAL

Sprifermin

Intervention Type DRUG

Participants received Sprifermin as intra-articular injection.

Placebo

Intervention Type DRUG

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

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.

Group Type PLACEBO_COMPARATOR

Sprifermin

Intervention Type DRUG

Participants received Sprifermin as intra-articular injection.

Interventions

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Sprifermin

Participants received Sprifermin as intra-articular injection.

Intervention Type DRUG

Placebo

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

Intervention Type DRUG

Other Intervention Names

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Recombinant Human Fibroblast Growth Factor-18 (rhFGF-18)

Eligibility Criteria

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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
Minimum Eligible Age

40 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Nordic Bioscience A/S

INDUSTRY

Sponsor Role collaborator

EMD Serono Research & Development Institute, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Responsible, MD

Role: STUDY_DIRECTOR

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

Locations

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Research site

Lakewood, Colorado, United States

Site Status

Research site

Baltimore, Maryland, United States

Site Status

Research site

Buenos Aires, , Argentina

Site Status

Research site

Brno, , Czechia

Site Status

Research site

Pardubice, , Czechia

Site Status

Research site

Prague, , Czechia

Site Status

Research site

Aalborg, , Denmark

Site Status

Research site

Ballerup Municipality, , Denmark

Site Status

Research site

Vejle, , Denmark

Site Status

Research site

Tallinn, , Estonia

Site Status

Research Site

Hong Kong, , Hong Kong

Site Status

Research site

Lodz, , Poland

Site Status

Research site

Bucharest, , Romania

Site Status

Countries

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United States Argentina Czechia Denmark Estonia Hong Kong Poland Romania

References

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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.

Reference Type DERIVED
PMID: 39734047 (View on PubMed)

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.

Reference Type DERIVED
PMID: 39286575 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33962962 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33752164 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32098758 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31593273 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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https://medical.emdserono.com/en_US/home.html

US Medical Information website, Medical Resources

Other Identifiers

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2011-003059-20

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

EMR700692_006

Identifier Type: -

Identifier Source: org_study_id

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