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

Osteoarthritis, Knee Clinical Trial

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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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01919164
• Other study ID #: EMR700692_006
• Secondary ID: 2011-003059-20
• Status: Completed
• Phase: Phase 2
• Start date: July 29, 2013
• Est. completion date: May 7, 2019

Study information

• Verified date: June 2020
• Source: EMD Serono
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 549
• Est. completion date: May 7, 2019
• Est. primary completion date: May 5, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Osteoarthritis
• Osteoarthritis, Knee

Intervention

Drug:
• Sprifermin
Participants received Sprifermin as intra-articular injection.
• Placebo
Participants received Placebo matched to sprifermin as intra-articular injection.

Locations

Country	Name	City	State
Argentina	Research site	Buenos Aires
Czechia	Research site	Brno
Czechia	Research site	Pardubice
Czechia	Research site	Prague
Denmark	Research site	Aalborg
Denmark	Research site	Ballerup
Denmark	Research site	Vejle
Estonia	Research site	Tallinn
Hong Kong	Research Site	Hong Kong
Poland	Research site	Lodz
Romania	Research site	Bucharest
United States	Research site	Baltimore	Maryland
United States	Research site	Lakewood	Colorado

Sponsors (2)

Lead Sponsor	Collaborator
EMD Serono Research & Development Institute, Inc.	Nordic Bioscience A/S

Countries where clinical trial is conducted

United States,  Argentina,  Czechia,  Denmark,  Estonia,  Hong Kong,  Poland,  Romania, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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	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.	Baseline, Week 52, Week 78 and Week 104
Secondary	Change From Baseline in the 20-meter Walk Test at 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.	Baseline, Week 12, 26, 38, 52, 64, 78, 90 and 104
Secondary	Change From Baseline in the Patient's Global Assessment (PGA) at 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.	Baseline, Week 12, 26, 38, 52, 64, 78, 90 and 104
Secondary	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	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).	Baseline, Week 52 and 104
Secondary	Change From Baseline in Cartilage Thickness in the Medial and Lateral Compartments as Well as in the Total Femorotibial Joint	The change in cartilage thickness was calculated based on quantitative magnetic resonance imaging (qMRI).	Medial and Lateral: Baseline, Week 26, 52, 78 and 104; Total: Baseline, Week 26, 52 and 78
Secondary	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	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.	Baseline, Week 26, 52, 78 and 104
Secondary	Synovial Fluid Levels of Sprifermin/FGF-18	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.	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)
Secondary	Serum Levels of Sprifermin/FGF-18		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)

External Links

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