Working... Menu

A Multicenter Study of rhFGF 18 in Patients With Knee Osteoarthritis Not Requiring Surgery

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01033994
Recruitment Status : Completed
First Posted : December 17, 2009
Last Update Posted : June 25, 2014
Information provided by (Responsible Party):
Merck KGaA, Darmstadt, Germany

Brief Summary:

Osteoarthritis (OA) is one of the most common diseases affecting the joints, usually those that are weight bearing such as the knees. OA is considered to be a disease of the cartilage in the joints even though it involves the whole joint, including the bone and synovium (thin lining of the joints which produces synovial fluid). With time, more and more of the cartilage is destroyed by the disease with inflammation commonly occurring.

AS902330 is expected to increase the production and development of specific bone cells: chondrocytes and osteoblasts (cells that produce and maintain bone and cartilage). This is expected to lead to repair and generation of the cartilage, and a narrowing of the space width between the knee joints in a selected region of the knee cartilage. The purpose of this study is to see how safe treatment with AS902330 is, and to evaluate its effect on the knee cartilage. In addition, the study will also measure the effects of AS902330 in the blood, which reflect disease activity.

Condition or disease Intervention/treatment Phase
Knee Osteoarthritis Biological: AS902330 Phase 1

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 192 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double Blind, Placebo-controlled, Multicenter, Single and Multiple Ascending Dose Study of AS902330 (rhFGF-18) Administered Intra-articularly in Patients With Primary Osteoarthritis of the Knee Who Are Not Expected to Require Knee Surgery Within One Year
Study Start Date : October 2008
Actual Primary Completion Date : October 2010
Actual Study Completion Date : December 2010

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Osteoarthritis

Arm Intervention/treatment
Experimental: AS902330 Biological: AS902330
10, 30 or 100 µg intra-articular injection per subject in the Single Ascending Dose (SAD) cohorts and 10, 30 or 100 µg intra-articular injection per week for three weeks per subject in the Multiple Ascending Dose (MAD) cohorts.
Other Names:
  • rhFGF 18
  • Recombinant human fibroblast growth factor 18
  • Sprifermin

Placebo Comparator: Placebo Biological: AS902330
10, 30 or 100 µg intra-articular injection per subject in the Single Ascending Dose (SAD) cohorts and 10, 30 or 100 µg intra-articular injection per week for three weeks per subject in the Multiple Ascending Dose (MAD) cohorts.
Other Names:
  • rhFGF 18
  • Recombinant human fibroblast growth factor 18
  • Sprifermin

Primary Outcome Measures :
  1. Change in cartilage thickness in the medial femoro-tibial compartment of the target knee joint, assessed by MRI [ Time Frame: 6 and 12 months after first injection ]
  2. Nature, incidence and severity of local and systemic treatment-emergent adverse events (TEAEs) [ Time Frame: MAD Cohorts: 1 year + 1 month; SAD Cohorts: 4 Weeks ]
  3. Proportion of subjects experiencing AIRs defined as increase of pain by 30mm on a 100mm visual analogue scale (VAS) associated with a self-reported synovial fluid effusion within 3 days following i.a. injection [ Time Frame: MAD Cohorts: Week 1, 2, 3, 13 14 and 15 (injections weeks); SAD Cohorts: Week 1 ]
  4. Laboratory assessments, including blood chemistry, hematology, urinalysis, and ECG [ Time Frame: MAD Cohorts: Week 0, 4, 13, 17, 52; SAD Cohorts: Weeks 0 & 4 ]

Secondary Outcome Measures :
  1. Change in cartilage thickness in the medial femoro-tibial compartment of the target knee joint, assessed by MRI [ Time Frame: 52 Weeks ]
  2. Change in total cartilage volume and thickness in the other compartments of the target knee joint, assessed by MRI [ Time Frame: 52 Weeks ]
  3. Change over time of structural as well as compositional parameters of the knee joint (e.g. cartilage and bone), evaluated by MRI [ Time Frame: 52 Weeks ]
  4. Change in WOMAC (Western Ontario MacMaster Osteoarthritis Questionaire) total score in the target knee from 5-point Likert scales [ Time Frame: 52 Weeks ]
  5. Change in WOMAC Function and Pain index scores in the target knee [ Time Frame: 52 Weeks ]
  6. Change in osteoarthritis (OA) pain in the target knee on a 100mm visual analogue scale (VAS) [ Time Frame: 52 Weeks ]
  7. Change in JSW in the target knee by x-ray [ Time Frame: 52 Weeks ]
  8. Presence of anti-AS902330 antibodies [ Time Frame: 52 Weeks ]
  9. Blood levels of AS902330 [ Time Frame: 52 Weeks ]
  10. MRI at 3 months, score on WOMAC questionnaire at 3, 6 and 12 months. [ Time Frame: 6 days ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   40 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Male or female >= 40 years of age; females must be postmenopausal or surgically sterile
  2. Established diagnosis of primary femoro-tibial OA of the target knee by standard American College of Rheumatology Criteria for at least six months (clinical AND radiological criteria)
  3. Radiological disease stage 2 or 3 (i.e., clear evidence of OA, but not most advanced disease) in the target knee according to the Kellgren-Lawrence grading of knee OA
  4. No major knee surgery (e.g., partial or total knee replacement, interventional arthroscopy) in the target knee planned for at least 12 months after first injection of the study drug
  5. Documented need for symptomatic PRN (as needed)-treatment for OA in the target knee with systemic non-steroidal anti-inflammatory drugs (NSAIDs) and/or other analgesics.
  6. Total WOMAC score between 24 and 72 (out of 96, corresponding to mild, moderate, or severe, but not extreme OA symptoms) for the target knee while on oral symptomatic treatment at baseline
  7. Full understanding of the requirements of the study and willingness to comply with all study visits and assessments
  8. Patients must have read and understood the informed consent form, and must have signed it prior to any study-related procedure

Exclusion Criteria:

  • any condition, including laboratory findings and findings in the medical history or in the pre-study assessments, that in the opinion of the Investigator constitutes a risk or contraindication for participation in the study or that could interfere with the study objectives, conduct or evaluation
  • clinically significant abnormal hematology (hemoglobin, leucocytes, and platelets), or blood chemistry values (aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), bilirubin, and creatinine
  • receipt of any investigational product or any experimental therapeutic procedure within the last 12 weeks preceding screening
  • participation in FIH study 27575 or in a different cohort of this study
  • i.a. treatment of the target knee with steroids or hyaluronic acid derivatives within the 3 months before baseline
  • for MAD cohorts, any contra-indications to MRI according to MRI guidelines
  • any condition that would interfere with efficacy or safety assessments in the target knee
  • any drug or food supplement with potential disease-modifying effect (glucosamine, diacerin, chondroitin sulfate) unless given at a stable dose over at least 4 weeks prior to first injection
  • use of electrotherapy or acupuncture for OA, unless there is a stable regimen for at least 4 weeks before baseline
  • any known active infections, including suspicion of intra-articular infection and/or infections that may compromise the immune system such as HIV, Hepatitis B or Hepatitis 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
  • signs and symptoms suggestive of transmissible spongiform encephalopathy
  • secondary osteoarthritis: e.g., joint dysplasias, aseptic osteonecrosis, acromegaly, Paget's disease, Ehlers-Danlos syndrome, Gaucher's disease, Stickler's syndrome, joint infection, hemophilia, hemochromatosis, calcium pyrophosphate deposition disease, or neuropathic arthropathy whatever the cause

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01033994

Layout table for location information
UMHAT "Sv. Ivan Rilski", Clinical Research Unit for Phase I
Sofia, Bulgaria, 1612
SKDS Research, Inc.
Newmarket, Canada
Kells Medical Research Group
Pointe Claire, Canada
Centre de rhumatologie St-Louis
Quebec, Canada
Groupe de Recherche en Maldies Osseuses de Quebec
Quebec, Canada
London Road Diagnostic Clinic
Sarnia, Canada
Albion Finch Medical Centre
Toronto, Canada
Clinical hospital Split
Split, Croatia
Clinical Hospital "Sestre Milosrdnice"
Zagreb, Croatia
Polyclinic for internal medicine, gynecology, radiology, physical medicine and rehabilitation
Zagreb, Croatia
Kuopio University Hospital, Department of Ortopaedics
Kuopio, Finland
Oulu University Hospital, Surgical and Intensive Care Division
Oulu, Finland
Turku University Central Hospital, Orthopedic Research Unit
Turku, Finland
PAREXEL International GmbH
Berlin, Germany, 14050
NZOZ Centrum Medyczne Artur Racewicz
Bialystok, Poland
Krakowskie Centrum Medyczne NZOZ
Cracow, Poland
REUMED Sp. z o.o.,
Lublin, Poland
Niepubliczny Zaklad Opieki Zdrowotnej Nasz Lekarz
Torun, Poland
Centrum Leczenia Chorob Cywilizacyjnych
Warsaw, Poland
Centrum Medyczne OSTEOMED Sp. z o.o.
Warsaw, Poland
Clinical Hospital Center Bezanijska Kosa
Beograd, Serbia
Institute of Rheumatology Resavska 69
Beograd, Serbia
• Name: Institute of diagnostic, prevention and rechabilitation of cardiovascular and rheumatoid diseases
Niska Banja, Serbia
South Africa
FARMOVS-PAREXEL (Pty) Ltd, University of the Free State
Bloemfontein, South Africa, 9301
George, South Africa, 6529
PAREXEL-Port Elizabeth, Mercantile Hospital
Port Elizabeth, South Africa, 6020
Ortopediska mottagningen
Hässleholm, Sweden
Kirurg- och ortopedkliniken Kungälvs sjukhus, 442 83 Kungälv
Kungälv, Sweden
Sponsors and Collaborators
Merck KGaA, Darmstadt, Germany
Layout table for investigator information
Study Director: Donatus Dreher, MD, PhD Merck Serono S.A., Geneva

Publications of Results:
Publications automatically indexed to this study by Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Merck KGaA, Darmstadt, Germany Identifier: NCT01033994     History of Changes
Other Study ID Numbers: 28980
First Posted: December 17, 2009    Key Record Dates
Last Update Posted: June 25, 2014
Last Verified: June 2014

Keywords provided by Merck KGaA, Darmstadt, Germany:
Knee osteoarthritis
Fibroblast growth factor 18

Additional relevant MeSH terms:
Layout table for MeSH terms
Osteoarthritis, Knee
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action