Clinical trial NCT01066871: Sprifermin (AS902330) in Cartilage Injury Repair (CIR)
Official title: A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Phase II Trial to Investigate the Efficacy and Safety of Weekly Intra-articular (i.a.) Injections of 10, 30, and 100 µg of AS902330 for Three Consecutive Weeks in Patients With Acute Cartilage Injury of the Knee
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Isolated Cartilage Injury of the Knee
Keywords: Knee cartilage injury
fibroblast growth factor 18
FGF18
Lead sponsor: Merck KGaA, Darmstadt, Germany
Sponsor class: INDUSTRY
First posted: 2010-02-10
Enrollment: 74
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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

Primary outcomes:
measure: Percent Change From Baseline in Cartilage Defect Volume at Month 12
timeFrame: Baseline, Month 12
Secondary outcomes:
measure: Percent Change From Baseline in Cartilage Defect Volume and Cartilage Defect Thickness in the Target Knee at Months 3 and 6
timeFrame: Baseline, Months 3 and 6
measure: Change From Baseline in Cartilage Defect Volume in the Target Knee at Months 3, 6 and 12
timeFrame: Baseline, Months 3, 6 and 12
measure: Change From Baseline in Cartilage Defect Thickness in the Target Knee at Months 3, 6 and 12
timeFrame: Baseline, Months 3, 6 and 12
measure: Number of Participants With Response to Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) Sub-scales
timeFrame: Months 3 (M3), 6 (M6) and 12 (M12)
measure: Change From Baseline in Boston Leeds Osteoarthritis Knee Score (BLOKS) Sub-scale (Bone Marrow Lesion [BML] Size, Osteophyte Size, Meniscal Extrusion Score [MES], and Meniscal Tear Score [MTS]) Scores at Month 12
timeFrame: Baseline, Month 12
measure: Number of Participants With Shift From Baseline in BLOKS Sub-Scales (Cartilage 1, Synovitis, Effusion) Scores at Month 12
timeFrame: Month 12
measure: Number of Participants With Change From Baseline in International Cartilage Repair Society (ICRS) Grade at Months 6 and 12
timeFrame: Baseline, Months 6 and 12
measure: Change From Baseline in Knee Injury and Osteoarthritis Outcome Score (KOOS) Sub-scale Scores and International Knee Documentation Committee (IKDC) Score at Months 3, 6 and 12
timeFrame: Baseline, Months 3, 6 and 12
measure: Number of Participants With Global Evaluation of Treatment Benefit
timeFrame: Months 3, 6 and 12
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Local TEAEs, Systemic TEAEs, TEAEs Leading to Discontinuation and Serious Adverse Events (SAEs)
timeFrame: Baseline up to Month 12
measure: Number of Participants With Acute Inflammatory Reactions
timeFrame: Baseline up to Month 12
measure: Number of Participants With Binding Antibodies (BAbs) and Neutralizing Antibodies (NAbs) to Fibroblast Growth Factor 18 (FGF18)
timeFrame: Week 1 (pre-dose), Week 2 (pre-dose), Week 4, Months 3 and 12
Other outcomes:
Locations:
city: Darmstadt
country: Germany
facility: Please contact the Merck KGaA Communication Center
Study officials:
affiliation: Merck KGaA, Darmstadt, Germany
name: Medical Responsible
role: STUDY_DIRECTOR
References: