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A Study to Investigate the Safety and Effectiveness of Different Doses of Sprifermin (AS902330) in Patients With Osteoarthritis of the Knee (FORWARD)

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01919164
First Posted: August 8, 2013
Last Update Posted: October 26, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
Nordic Bioscience A/S
Information provided by (Responsible Party):
EMD Serono
  Purpose
This is a multicenter, randomized, double-blind, placebo-controlled, parallel-group Phase 2 trial of AS902330 administered intra-articularly in subjects with primary osteoarthritis of the knee and Kellgren-Lawrence Grade 2 or 3. The trial is intended to investigate the efficacy and safety of different intra articular dosages of AS902330 (Sprifermin) in these individuals.

Condition Intervention Phase
Osteoarthritis, Knee Drug: AS902330 100 microgram (mcg) Drug: AS902330 30 microgram (mcg) Drug: Placebo Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by EMD Serono:

Primary Outcome Measures:
  • Change from Baseline in cartilage thickness in the total femorotibial joint as evaluated by MRI at 2 years [ Time Frame: Baseline and 2 years ]

Secondary Outcome Measures:
  • Changes from Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score and in the WOMAC pain, function, and stiffness index scores up to 2 years [ Time Frame: Up to 2 years ]
  • Change from Baseline in the 20-meter walk test up to 2 years [ Time Frame: Up to 2 years ]
  • Change from Baseline in the Patient's Global Assessment (PGA) up to 2 years [ Time Frame: Up to 2 years ]
  • Change from Baseline in minimal joint space width (JSW) in the medial and lateral compartments as evaluated by X-ray up to 2 years [ Time Frame: Up to 2 years ]
  • Change from Baseline in cartilage thickness in the medial and lateral compartments as well as in the total femorotibial joint up to 2 years [ Time Frame: Up to 2 years ]
  • Change from Baseline in cartilage volume in the medial and lateral compartments as well as in the total femorotibial joint up to 2 years [ Time Frame: Up to 2 years ]
  • Synovial fluid levels of AS902330 [ Time Frame: Up to 2 years ]
  • Serum levels of AS902330 [ Time Frame: Up to 2 years ]
  • Number of Subjects with Adverse Events [ Time Frame: Up to Week 260 ]

Enrollment: 549
Actual Study Start Date: July 31, 2013
Estimated Study Completion Date: May 20, 2019
Primary Completion Date: May 5, 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment Arm 1: AS902330 (100 mcg)
AS902330 will be administered at a dose of 100 microgram (mcg) in 4 cycles, wherein each cycle will include 3 once-weekly intra-articular injections over a period of 3 consecutive weeks, with follow-up to 2 years.
Drug: AS902330 100 microgram (mcg)
AS902330 will be administered at a dose of 100 mcg in 4 cycles (at Baseline and Months 6, 12, and 18), wherein each cycle will include 3 once-weekly intra-articular injections over a period of 3 consecutive weeks, with follow-up to 2 years.
Other Names:
  • Sprifermin
  • Recombinant Human Fibroblast Growth Factor-18 (rhFGF-18)
Experimental: Treatment Arm 2 : AS902330 (100 mcg) alternating with placebo
AS902330, 100 mcg, will be administered in Cycles 1 and 3 and matching placebo will be administered in Cycles 2 and 4, wherein each cycle will include 3 once-weekly intra-articular injections over a period of 3 consecutive weeks, with follow-up to 2 years.
Drug: AS902330 100 microgram (mcg)
AS902330 will be administered at a dose of 100 mcg in 2 cycles (at Baseline and Month 12), wherein each cycle will include 3 once-weekly intra-articular injections over a period of 3 consecutive weeks, with follow-up to 2 years.
Other Names:
  • Sprifermin
  • rhFGF-18
Drug: Placebo
Matching placebo will be administered in 2 cycles (at Months 6 and 18), wherein each cycle will include 3 once-weekly intra-articular injections over a period of 3 consecutive weeks, with follow-up to 2 years.
Experimental: Treatment Arm 3: AS902330 (30 mcg)
AS902330 will be administered at a dose of 30 microgram (mcg) in 4 cycles, wherein each cycle will include 3 once-weekly intra-articular injections over a period of 3 consecutive weeks, with follow-up to 2 years.
Drug: AS902330 30 microgram (mcg)
AS902330 will be administered at a dose of 30 mcg in 4 cycles (at Baseline and Months 6, 12, and 18), wherein each cycle will include 3 once-weekly intra-articular injections over a period of 3 consecutive weeks, with follow-up to 2 years.
Other Names:
  • Sprifermin
  • rhFGF-18
Experimental: Treatment Arm 4 : AS902330 (30 mcg) alternating with placebo
AS902330, 30 mcg, will be administered in Cycles 1 and 3 and matching placebo will be administered in Cycles 2 and 4, wherein each cycle will include 3 once-weekly intra-articular injections over a period of 3 consecutive weeks, with follow-up to 2 years.
Drug: AS902330 30 microgram (mcg)
AS902330 will be administered at a dose of 30 mcg in 2 cycles (at Baseline and Month 12), wherein each cycle will include 3 once-weekly intra-articular injections over a period of 3 consecutive weeks, with follow-up to 2 years.
Other Names:
  • Sprifermin
  • rhFGF-18
Drug: Placebo
Matching placebo will be administered in 2 cycles (at Months 6 and 18), wherein each cycle will include 3 once-weekly intra-articular injections over a period of 3 consecutive weeks, with follow-up to 2 years.
Placebo Comparator: Arm 5: Placebo
Matching Placebo will be administered in 4 cycles, wherein each cycle will include 3 once-weekly intra-articular injections over a period of 3 consecutive weeks, with follow-up to 2 years.
Drug: Placebo
Matching placebo will be administered in 4 cycles (at Baseline and Months 6, 12, and 18), wherein each cycle will include 3 once-weekly intra-articular injections over a period of 3 consecutive weeks, with follow-up to 2 years.

Detailed Description:
Subjects will be 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.
  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   40 Years to 85 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01919164


Locations
United States, Colorado
Research site
Lakewood, Colorado, United States
Czechia
Research site
Brno, Czechia
Research site
Pardubice, Czechia
Research site
Prague, Czechia
Denmark
Research site
Aalborg, Denmark
Research site
Vejle, Denmark
Estonia
Research site
Tallinn, Estonia
Hong Kong
Research Site
Hong Kong, Hong Kong
Poland
Research site
Lodz, Poland
Romania
Research site
Bucharest, Romania
Sponsors and Collaborators
EMD Serono
Nordic Bioscience A/S
Investigators
Study Director: Medical Responsible, MD Merck KGaA
  More Information

Responsible Party: EMD Serono
ClinicalTrials.gov Identifier: NCT01919164     History of Changes
Other Study ID Numbers: EMR700692_006
2011-003059-20 ( EudraCT Number )
First Submitted: August 7, 2013
First Posted: August 8, 2013
Last Update Posted: October 26, 2017
Last Verified: October 2017

Keywords provided by EMD Serono:
Osteoarthritis of knee
AS902330
Recombinant Human Fibroblast Growth Factor-18 (rhFGF-18)
Sprifermin
Placebo

Additional relevant MeSH terms:
Osteoarthritis
Osteoarthritis, Knee
Arthritis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Mitogens
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action