A Multicenter Trial of Sprifermin (AS902330 [Recombinant Human Fibroblast Growth Factor-18]) or Placebo After Microfracture Surgery for Cartilage Injury of the Knee

Phase 2TerminatedNCT01689337

EMD Serono1 enrolled

Overview

This is a Phase 2, double-blind, multicenter, randomized, placebo-controlled trial to evaluate the efficacy and safety of Sprifermin (AS902330) (recombinant human fibroblast growth factor-18 \[rhFGF-18\]) as an adjunct treatment to subjects following microfracture (MFx) surgery for cartilage injury of the knee. Primary Objectives * To evaluate the effect of Sprifermin (AS902330) intra-articular knee injections as adjunct to microfracture (MFx) surgery on the composition of the refilled cartilage in the target knee, as measured by gadolinium-enhanced magnetic resonance imaging (MRI) of cartilage (dGEMRIC) time constant 1 (T1) relaxation time at 6 months after MFx surgery * To evaluate the safety profile of Sprifermin (AS902330) when administered intra-articular into the knee as adjunct to MFx surgery in subjects with cartilage injury of the knee Secondary Objectives * To further support the efficacy and safety of Sprifermin (AS902330) as an adjunct to MFx for cartilage injury repair through symptomatic outcomes and quantitative MRI measurement

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Cartilage Injury of Knee

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 60 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Subjects with candidature for MFx surgery on the femoral articular surfaces (medial or lateral condyles or trochlear groove), with intact subchondral bone * Subjects with moderate to severe pain in the target knee prior to surgery; average score greater than equal to (\>=) 4.0 over 7 consecutive days on numeric rating scale of pain intensity (completed within 30 \[+15\] days before surgery) * Intraoperative inclusion criteria: Subjects with 1 or 2 focal chondral lesions per target knee, where peripheral debridement to healthy cartilage results in all of the following: * Each lesion has an area of \>= 1 square centimeter (cm\^2) and less than equal to (\<=) 4 cm\^2 * Each lesion is \<= 6 millimeter (mm) in depth, as measured from the surrounding subchondral plate * Arthroscopic confirmation that each non-osteochondritis dissecans (OCD) lesion is between International Cartilage Repair Society (ICRS) Grades I and III (D); a Grade III non-OCD lesion is equivalent to an Outerbridge Grade IV lesion with minimal subchondral bone loss * Other protocol-defined inclusion criteria could apply Exclusion Criteria: * Subjects with prior marrow stimulation treatment of the target knee, that is, MFx, micro-drilling, abrasion chondroplasty or cartilage repair including, but not limited to, autologous chondrocyte implantation (ACI), matrix/membrane autologous chondrocyte implantation (MACI), or osteochondral transplantation (autologous or allogeneic) * Subjects with body mass index (BMI) of greater than 35 kilogram per square meter (kg/m\^2) at screening * Malalignment of the target knee greater than 5 degrees as measured from the mechanical axis, as confirmed by alignment (long bone) X-ray images * Subjects with clinical and/or radiographic disease diagnosis of the target knee joint including, but not limited to the following: generalized osteoarthritis (OA), rheumatoid arthritis, or avascular necrosis * Subjects who have any contraindication to MRI or gadolinium-based or iodinated contrast agents according to the site's standard practice guidelines * Other protocol-defined exclusion criteria could apply

Outcomes

Primary Outcomes

Composition of the Refilled Cartilage Measured by Delayed Gadolinium-Enhanced Magnetic Resonance Imaging of Cartilage (dGEMRIC) Using T1 Relaxation Time at Month 6 Post-MFx Surgery

The dGEMRIC is an imaging technique that estimates the proteoglycan (and glycosaminoglycan) content of joint cartilage using spin-lattice relaxation time T1 after penetration of gadolinium contrast agent. Composition of the refilled cartilage was to be reported.

Time frame: 6 months post-MFx surgery

Secondary Outcomes

Composition of the Refilled Cartilage Measured by dGEMRIC Using T1 Relaxation Time Beyond Month 6 Post-MFx Surgery

Time frame: Every 6 months up to 5 years beyond 6 months post-MFx surgery

Change From Baseline in Participant-reported Outcome Measure: Knee Injury and Osteoarthritis Outcome Score (KOOS) Sub-scores for Pain and Activities of Daily Living (ADL)

The KOOS Version LK1.0 is a knee-specific self-administered questionnaire used to assess pain, function, quality of life, and ADL. It consists of 42 items grouped into 5 subscales: pain, other symptoms (including swelling, restricted range of motion, and mechanical symptoms), function in ADL, function in sport and recreation (FSR), and impact on quality of life (QOL) (knee-related QOL, including awareness of the knee condition and changes in lifestyle). The subscales are scored separately; each yields a score between 0 and 100, with 0 representing extreme knee problems and 100 representing absence of problems. Total KOOS score is the average of all 5 subscale scores; ranging from 0 to 100; where 0 represents extreme knee problems and 100 represents absence of knee problems. Change from baseline in pain and ADL sub-scores was to be calculated by the respective scores at the specific time point minus the scores at baseline.