Sprifermin (AS902330) in Cartilage Injury Repair (CIR)
Condition: Isolated Cartilage Injury of the Knee
MeSH terms: Wounds and Injuries
Intervention: Sprifermin (AS902330) 10 mcg; Sprifermin (AS902330) 30 mcg; Sprifermin (AS902330) 100 mcg; Placebo
Intervention description: Sprifermin (AS902330) will be administered at a dose of 10 microgram (mcg) as intra-articular injection once every week for 3 consecutive weeks.; Sprifermin (AS902330) will be administered at a dose of 30 mcg as intra-articular injection once every week for 3 consecutive weeks.; Sprifermin (AS902330) will be administered at a dose of 100 mcg as intra-articular injection once every week for 3 consecutive weeks.; Placebo matched to sprifermin (AS902330) will be administered as intra-articular injection once every week for 3 consecutive weeks.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 74.0
Sex: All
Minimum age: 18 Years
Maximum age: 45 Years
Healthy volunteers: No
Keywords: Knee cartilage injury; fibroblast growth factor 18; FGF18

Summary:

      Several people all over the world suffer from cartilage injuries in the knee. Symptoms
      include pain, joint swelling, and loss of function. Without repair, cartilage injury may
      ultimately lead to osteoarthritis (OA). Natural healing is poor, and to date treatment is
      available only for deep cartilage defects involving also the underlying bone. A promising
      candidate for drug treatment of cartilage injury is sprifermin (AS902330), a recombinant form
      of the human fibroblast growth factor (FGF) 18.

      So far, the drug has been used in subjects with different stages of knee OA in two ongoing
      studies without emerging safety issues following single and multiple intra-articular
      injections of ascending doses. However, OA represents late-stage cartilage injury, where
      repair might be difficult due to diffuse damage, reduced responsiveness of the cartilage,
      and/or the involvement of other joint structures.

      This clinical trial is meant to provide the proof of concept and to identify an efficacious
      dose of sprifermin (AS902330) for the treatment of adult subjects with acute cartilage
      injuries of the knee. The first subject for this trial was treated on the 19th of April 2010.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Acute cartilage lesion of ICRS grade 2 to 4 at the femoral condyle of the knee (=
             target knee)

          -  Age: 18 to 45 years

          -  Sex: male or female. Women of childbearing potential (that is, all female subjects
             after puberty unless they are post-menopausal for at least 2 years or surgically
             sterile) must have negative serum and urine pregnancy tests at screening and Visit 1,
             respectively, and must use a highly effective method of contraception.

          -  History of pain and effusion of the target knee post-injury

          -  Injury within 4 to 12 weeks prior to 1st treatment with investigational medicinal
             product (IMP)

          -  Written informed consent prior to any trial-related activity

        Exclusion Criteria:

          -  Personal medical history of osteoarthritis OA in either knee

          -  Any previous surgery on the target knee

          -  History of swelling of the target knee along with pain on weight-bearing, or
             arthroscopy for diagnostic purposes during the 12 months preceding injury

          -  Corticosteroid (intra-articular) injection into the target knee during the preceding
             12 months

          -  Any other intra-articular injection into the target knee during the preceding 3 months

          -  Any concurrent injury (for example, arthrolith, anterior cruciate ligament rupture,
             meniscus tear) of the target knee requiring surgical intervention

          -  OA or any pre-existing cartilage damage in the target knee, as revealed by MRI

          -  Legal incapacity or limited legal capacity

          -  Subjects who are imprisoned or institutionalized by regulatory or court order

          -  Pregnancy or lactation

          -  Participation in another clinical trial within the past 30 days

          -  Any condition or findings in the medical history or in the pre-trial assessments that
             in the opinion of the Investigator constitutes a risk or contraindication for
             participation in the trial or that could interfere with the trial objectives, conduct
             or evaluation

          -  Known hypersensitivity to the trial treatment or diluents

          -  Significant renal or hepatic impairment, as indicated by: Aspartate aminotransferase
             (AST), alanine aminotransferase (ALT), or alkaline phosphatase (ALP) greater than (>)
             3 times the upper limit of normal (ULN); total bilirubin >1.5 times ULN (except in
             case of Gilbert's syndrome); creatinine >1.5 times ULN; hemoglobin less than (<5.5)
             millimole per liter (mmol/L), white blood cell count (WBC) <2.5 * 10^9 per liter, or
             platelets <75 *10^9 per liter)

          -  Any suspicion of intra-articular infection

          -  Any known active infections that may compromise the immune system such as human
             immunodeficiency virus (HIV), Hepatitis B or C infection

          -  History of sarcoma and/or of other active malignancy within five years, except
             adequately treated basal cell or squamous cell carcinoma of the skin

          -  Open growth plate, as revealed by MRI

          -  Diagnostic arthroscopy after injury and within 4 weeks prior to treatment start