AS902330 in Cartilage Injury Repair (CIR)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck KGaA
ClinicalTrials.gov Identifier:
NCT01066871
First received: February 9, 2010
Last updated: October 14, 2013
Last verified: October 2013
  Purpose

Many 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 AS902330, a recombinant form of the human fibroblast growth factor (FGF) 18.

So far, the drug has been used in patients with different stages of knee OA in two ongoing studies without emerging safety issues following single and multiple i.a. 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 AS902330 for the treatment of adult patients (21 to 40 years old) with acute cartilage injuries of the knee. The 1st patient for this trial was treated on the 19th of April 2010.


Condition Intervention Phase
Isolated Cartilage Injury of the Knee
Drug: AS902330
Other: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Merck KGaA:

Primary Outcome Measures:
  • The relative change in cartilage defect volume over 12 months based on central magnetic resonance imaging (MRI). [ Time Frame: 12 Months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Efficacy: - The relative and absolute changes in cartilage defect volume and thickness in the target knee from baseline to 6 months and the absolute changes over 12 months [ Time Frame: 12 Months ] [ Designated as safety issue: No ]
  • Efficacy: - Changes in the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score for the integration of rebuilt cartilage and its surface structure at 3, 6 and 12 months [ Time Frame: 12 Months ] [ Designated as safety issue: No ]
  • Efficacy: Changes in the Boston Leeds Osteoarthritis Knee Score (BLOKS) at 12 months [ Time Frame: 12 Months ] [ Designated as safety issue: No ]
  • Efficacy: Changes in ICRS (International Cartilage Repair Society) grades over 6 and 12 months [ Time Frame: 12 Months ] [ Designated as safety issue: No ]
  • Efficacy: The relative and absolute change in cartilage defect volume/thickness in the target knee from baseline to 3 months [ Time Frame: 12 Months ] [ Designated as safety issue: No ]
  • Efficacy: Changes in symptom scores (Knee Injury and Osteoarthritis Outcome Score [KOOS], International Knee Documentation Committee [IKDC], global evaluation of treatment benefit) at visits over 12 months [ Time Frame: 12 Months ] [ Designated as safety issue: No ]
  • Safety: Systemic and local AEs over 12 months [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Safety: Acute inflammatory events, i.e., increase of pain of at least 30 mm on a 100 mm visual analog scale (VAS) along with self-reported swelling within 3 days post-injection [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Safety: Changes in safety laboratory measurements and vital signs over 12 months [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Safety: Occurrence of antibodies to FGF18 [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Enrollment: 591
Study Start Date: March 2010
Study Completion Date: April 2013
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A Drug: AS902330
Once a week an intra-articular injection of 10µg AS902330 over three consecutive weeks.
Experimental: B Drug: AS902330
Once a week an intra-articular injection of 30µg AS902330 over three consecutive weeks.
Experimental: C Drug: AS902330
Once a week an intra-articular injection of 100µg AS902330 over three consecutive weeks.
Placebo Comparator: D Other: Placebo
Once a week an intra-articular injection of Placebo over three consecutive weeks.

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

For inclusion, all of the following criteria must be fulfilled:

  1. Acute cartilage lesion of International Cartilage Injury Society (ICRS) grade 2 to 4 at the femoral condyle of the knee (= target knee)
  2. Age: 18 to 45 years
  3. Sex: male or female. Women of childbearing potential (i.e. all female patients after puberty unless they are post-menopausal for at least two 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.
  4. History of pain and effusion of the target knee post-injury
  5. Injury within 4 to 12 weeks prior to 1st treatment with IMP investigational medicinal product (IMP)
  6. Written informed consent prior to any trial-related activity

Exclusion Criteria:

Patients are not eligible for this trial if they fulfill any of the following criteria:

  1. Personal medical history of osteoarthritis OA in either knee
  2. Any previous surgery on the target knee
  3. History of swelling of the target knee along with pain on weight-bearing, or arthroscopy for diagnostic purposes during the 12 months preceding injury
  4. Corticosteroid (intraarticular [i.a.]) injection into the target knee during the preceding 12 months
  5. Any other i.a. injection into the target knee during the preceding 3 months
  6. Any concurrent injury (e.g. arthrolith, anterior cruciate ligament rupture, meniscus tear) of the target knee requiring surgical intervention
  7. OA or any pre-existing cartilage damage in the target knee, as revealed by MRI
  8. Legal incapacity or limited legal capacity
  9. Patients who are imprisoned or institutionalized by regulatory or court order
  10. Pregnancy or lactation
  11. Participation in another clinical trial within the past 30 days
  12. 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
  13. Known hypersensitivity to the trial treatment or diluents
  14. Significant renal or hepatic impairment, as indicated by
  15. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), or alkaline phosphatase (AP) >3 times the upper limit of normal (ULN)
  16. Total bilirubin >1.5 times ULN (except in case of Gilbert's syndrome)
  17. Creatinine >1.5 times ULN
  18. Hemoglobin <5.5 mmol/L, white blood cell count (WBC) <2.5 x 109/L, or platelets <75 x 109/L).
  19. Any suspicion of i.a. infection
  20. Any known active infections that may compromise the immune system such as HIV, Hepatitis B or C infection
  21. History of sarcoma and/or of other active malignancy within five years, except adequately treated basal cell or squamous cell carcinoma of the skin
  22. Open growth plate, as revealed by MRI
  23. Diagnostic arthroscopy after injury and within 4 weeks prior to treatment start
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01066871

Locations
Switzerland
Please call / email Central Contact for Recruiting Information which is located in
Geneva, Switzerland
Sponsors and Collaborators
Merck KGaA
Investigators
Study Director: Alexander M. Lai, MD, PhD EMD Serono Inc., an Affiliate of Merck KGaA, Darmstadt, Germany
  More Information

No publications provided

Responsible Party: Merck KGaA
ClinicalTrials.gov Identifier: NCT01066871     History of Changes
Other Study ID Numbers: EMR700692_003
Study First Received: February 9, 2010
Last Updated: October 14, 2013
Health Authority: Bulgaria: Bulgarian Drug Agency, Ethics Committee for Multicenter Trials
Canada: Health Canada, Ethics Review Committee
Germany: Bundesinstitut für Arzneimittel und Medizinproduckte (BfArM), Federal Institute for Drugs and Medical Devices, Ethics Commission
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Ethics Review Committee
Serbia: Agency for Drugs and Medicinal Devices, Ethics Review Committee
South Africa: Medicines Control Council, Ethics Committee of the University of the Free State
Slovenia: Agency for Medicinal Products - Ministry of Health
Hungary: National Institute of Pharmacy

Keywords provided by Merck KGaA:
Knee cartilage injury
fibroblast growth factor 18
FGF18

Additional relevant MeSH terms:
Wounds and Injuries

ClinicalTrials.gov processed this record on April 22, 2014