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Completed

NCT Number: NCT01919164

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

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.

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Key information

Conditions

Osteoarthritis, Knee Arthritis Joint Diseases Musculoskeletal Diseases Osteoarthritis Rheumatic Diseases

Age range

40 year–85 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Research site, Buenos Aires, Argentina

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Sprifermin

Drug

Participants received Sprifermin as intra-articular injection.

Other names: Recombinant Human Fibroblast Growth Factor-18 (rhFGF-18)

Placebo

Drug

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

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

    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

  1. 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

    Time frame: Baseline, Week 52, Week 78 and Week 104

    WOMAC pain subscale consists of 5 questions (Likert Scale) relating to pain. Sum of items of pain subscale ranges from 0-11. Higher scores=worse pain. Stiffness subscale consists of 2 questions relating articular function. Sum of items of stiffness subscale ranges from 0-8. Higher scores=worse function. Physical function subscale consists of 17 question relating to physical activities. Sum of items of physical function subscale ranges from 0-68. Higher scores= worse functional limitations. Each sub-scale is directly transformed into a 0-100 scale, where higher score indicates worse condition. WOMAC total score(24questions) is sum of total subscales which was directly transformed into score range from 0-100. Higher scores=worse condition. Negative value in change is indicative of improvement.

  2. Change From Baseline in the 20-meter Walk Test at Week 12, 26, 38, 52, 64, 78, 90 and 104

    Time frame: Baseline, Week 12, 26, 38, 52, 64, 78, 90 and 104

    The 20-meter walk test is an objective test of physical function which consists of measuring the time needed for the participant to walk 20 meters at a normal pace. A stopwatch was used for time measurement.

  3. Change From Baseline in the Patient's Global Assessment (PGA) at Week 12, 26, 38, 52, 64, 78, 90 and 104

    Time frame: Baseline, Week 12, 26, 38, 52, 64, 78, 90 and 104

    The Patient Global Assessment is based on participant's answer to the question "Considering all the ways your osteoarthritis of the knee has affected you during the last 48 Hours, select the number that best describes the impact of your knee osteoarthritis on your daily life", and can take on values between 0-10 (0=None, 10=Extreme), for summaries the values are rescaled to 0-100 by multiplication with 10. Higher scores indicated worsening of condition. A negative value in change in Patient's Global Assessment is indicative of an improvement.

  4. 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

    Time frame: Baseline, Week 52 and 104

    Change in joint space narrowing was visualized with the "fixed flexion" knee radiograph. Determination of joint space narrowing by X-ray is considered to be a semi-quantitative method for assessment of progression of knee Osteoarthritis (OA). X-rays of both the target knee and the contralateral knee were performed. X-rays were read centrally. X-ray images were used to measure mJSW in the medial femorotibial and lateral femorotibial compartments and to determine the participant's baseline Kellgren-Lawrence grades (KLG).

  5. Change From Baseline in Cartilage Thickness in the Medial and Lateral Compartments as Well as in the Total Femorotibial Joint

    Time frame: Medial and Lateral: Baseline, Week 26, 52, 78 and 104; Total: Baseline, Week 26, 52 and 78

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

  6. 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

    Time frame: Baseline, Week 26, 52, 78 and 104

    The change in cartilage volume in the medial and lateral compartments as well as in the total femorotibial joint at Week 26, 52, 78 and 104 was calculated based on qMRI.

  7. Synovial Fluid Levels of Sprifermin/FGF-18

    Time frame: 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)

    Levels of sprifermin/FGF-18 in synovial fluid were measured to provide a first estimate of the residence time of sprifermin in the synovial fluid.

  8. Serum Levels of Sprifermin/FGF-18

    Time frame: 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)

Sponsors and collaborators

Lead sponsor

EMD Serono Research & Development Institute, Inc.

Industry

Collaborators

  • Nordic Bioscience A/S

Registry information

Official study 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

Acronym: FORWARD

Important dates

Study start
2013
Primary completion
2016
Study completion
2019
First posted
Aug 8, 2013
Registry last updated
Jul 13, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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