Clinical trial NCT01689337: A Multicenter Trial of Sprifermin (AS902330 [Recombinant Human Fibroblast Growth Factor-18]) or Placebo After Microfracture Surgery for Cartilage Injury of the Knee
Official title: A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel Group, Phase II Trial to Investigate the Efficacy and Safety of 30 mcg and 100 mcg AS902330 Given as One Cycle of Three Intra-articular Knee Injections Once a Week for Three Weeks as an Adjunct Treatment to Patients Following Microfracture Surgery for Cartilage Injury of the Knee.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Cartilage Injury of Knee
Keywords: Microfracture surgery
Cartilage repair
Knee surgery
Lead sponsor: EMD Serono
Sponsor class: INDUSTRY
First posted: 2012-09-21
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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


Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: 6 months post-MFx surgery
Secondary outcomes:
measure: Composition of the Refilled Cartilage Measured by dGEMRIC Using T1 Relaxation Time Beyond Month 6 Post-MFx Surgery
timeFrame: Every 6 months up to 5 years beyond 6 months post-MFx surgery
measure: 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)
timeFrame: Every 6 months up to 5 years
measure: Change From Baseline in Participant-reported Outcome Measure: Total KOOS Score, Three KOOS Sub-scores and Total KOOS Minus FSR Sub-score
timeFrame: Every 6 months up to 5 years
measure: Change From Baseline in Participant-reported Outcome Measure: Numeric Rating Scale (NRS) Score
timeFrame: Every 6 months up to 5 years
measure: Change From Baseline in Participant-reported Outcome Measure: Lower Extremity Activity Scale (LEAS) Score
timeFrame: Every 6 months up to 5 years
measure: Change From Baseline in the Physician-reported Outcome Measure: Lysholm Knee Scale Score
timeFrame: Every 6 months up to 5 years
measure: Composition of the Refilled Cartilage Using T2 Mapping
timeFrame: Every 6 months up to 5 years
measure: Volume of the Refilled Cartilage
timeFrame: Every 6 months up to 5 years
measure: Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) Score
timeFrame: Every 6 months up to 5 years
measure: Six-minute Walk Test
timeFrame: Every 3 months up to 5 years beyond Month 6 post-MFx surgery
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Baseline up to Month 60
Other outcomes:
Locations:
Study officials:
affiliation: EMD Serono, Inc., Rockland MA, a subsidiary of Merck KGaA, Darmstadt, Germany
name: Medical Responsible
role: STUDY_DIRECTOR
References: