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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck KGaA
ClinicalTrials.gov Identifier:
NCT01033994
First received: December 16, 2009
Last updated: June 24, 2014
Last verified: June 2014
  Purpose

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 Intervention Phase
Knee Osteoarthritis
Biological: AS902330
Phase 1

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 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

Resource links provided by NLM:


Further study details as provided by Merck KGaA:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]
  • Laboratory assessments, including blood chemistry, hematology, urinalysis, and ECG [ Time Frame: MAD Cohorts: Week 0, 4, 13, 17, 52; SAD Cohorts: Weeks 0 & 4 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Change in cartilage thickness in the medial femoro-tibial compartment of the target knee joint, assessed by MRI [ Time Frame: 52 Weeks ] [ Designated as safety issue: Yes ]
  • Change in total cartilage volume and thickness in the other compartments of the target knee joint, assessed by MRI [ Time Frame: 52 Weeks ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]
  • Change in WOMAC (Western Ontario MacMaster Osteoarthritis Questionaire) total score in the target knee from 5-point Likert scales [ Time Frame: 52 Weeks ] [ Designated as safety issue: Yes ]
  • Change in WOMAC Function and Pain index scores in the target knee [ Time Frame: 52 Weeks ] [ Designated as safety issue: Yes ]
  • Change in osteoarthritis (OA) pain in the target knee on a 100mm visual analogue scale (VAS) [ Time Frame: 52 Weeks ] [ Designated as safety issue: Yes ]
  • Change in JSW in the target knee by x-ray [ Time Frame: 52 Weeks ] [ Designated as safety issue: Yes ]
  • Presence of anti-AS902330 antibodies [ Time Frame: 52 Weeks ] [ Designated as safety issue: Yes ]
  • Blood levels of AS902330 [ Time Frame: 52 Weeks ] [ Designated as safety issue: Yes ]
  • MRI at 3 months, score on WOMAC questionnaire at 3, 6 and 12 months. [ Time Frame: 6 days ] [ Designated as safety issue: Yes ]

Enrollment: 192
Study Start Date: October 2008
Study Completion Date: December 2010
Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01033994

Locations
Bulgaria
UMHAT "Sv. Ivan Rilski", Clinical Research Unit for Phase I
Sofia, Bulgaria, 1612
Canada
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
Croatia
Clinical hospital Split
Split, Croatia
Polyclinic for internal medicine, gynecology, radiology, physical medicine and rehabilitation
Zagreb, Croatia
Clinical Hospital "Sestre Milosrdnice"
Zagreb, Croatia
Finland
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
Germany
PAREXEL International GmbH
Berlin, Germany, 14050
Poland
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
Serbia
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
PAREXEL -George
George, South Africa, 6529
PAREXEL-Port Elizabeth, Mercantile Hospital
Port Elizabeth, South Africa, 6020
Sweden
Ortopediska mottagningen
Hässleholm, Sweden
Kirurg- och ortopedkliniken Kungälvs sjukhus, 442 83 Kungälv
Kungälv, Sweden
Sponsors and Collaborators
Merck KGaA
Investigators
Study Director: Donatus Dreher, MD, PhD Merck Serono S.A., Geneva
  More Information

Publications:
Responsible Party: Merck KGaA
ClinicalTrials.gov Identifier: NCT01033994     History of Changes
Other Study ID Numbers: 28980
Study First Received: December 16, 2009
Last Updated: June 24, 2014
Health Authority: Bulgaria: Bulgarian Drug Agency
Canada: Health Canada
Croatia: Ministry of Health and Social Care
Germany: Federal Institute for Drugs and Medical Devices
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Serbia and Montenegro: Agency for Drugs and Medicinal Devices
South Africa: Medicines Control Council
Sweden: Regional Ethical Review Board
United States: Food and Drug Administration
Finland: Finnish Medicines Agency

Keywords provided by Merck KGaA:
Knee osteoarthritis
Fibroblast growth factor 18
Sprifermin

Additional relevant MeSH terms:
Osteoarthritis
Osteoarthritis, Knee
Arthritis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Mitogens
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 30, 2014