A Multicenter Trial of Sprifermin (AS902330 [Recombinant Human Fibroblast Growth Factor-18]) or Placebo After Microfracture Surgery for Cartilage Injury of the Knee
Condition: Cartilage Injury of Knee
MeSH terms: Wounds and Injuries; Fractures, Stress
Intervention: Sprifermin (AS902330); Sprifermin (AS902330); Placebo
Intervention description: Sprifermin (AS902330) will be administered at a dose of 30 microgram (mcg) as intra-articular injection once every week for 3 weeks, starting from 2 weeks after MFx surgery.; Sprifermin (AS902330) will be administered at a dose of 100 mcg as intra-articular injection once every week for 3 weeks, starting from 2 weeks after MFx surgery.; Placebo matched to Sprifermin (AS902330) will be administered as intra-articular injection once every week for 3 weeks, starting from 2 weeks after MFx surgery.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 1.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: No
Keywords: Microfracture surgery; Cartilage repair; Knee surgery

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