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

NCT01033994 | Completed Phase 1

• 1 other identifier: 28980
• Study Type: interventional
• Target: 192
• Locations: 8 countries
• Sites: 25

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.

Conditions

Knee Osteoarthritis

Keywords

Knee osteoarthritis; Fibroblast growth factor 18; Sprifermin

Outcome Measures

Primary Outcomes (4)

• Change in cartilage thickness in the medial femoro-tibial compartment of the target knee joint, assessed by MRI

  6 and 12 months after first injection

• Nature, incidence and severity of local and systemic treatment-emergent adverse events (TEAEs)

  MAD Cohorts: 1 year + 1 month; SAD Cohorts: 4 Weeks

• 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

  MAD Cohorts: Week 1, 2, 3, 13 14 and 15 (injections weeks); SAD Cohorts: Week 1

• Laboratory assessments, including blood chemistry, hematology, urinalysis, and ECG

  MAD Cohorts: Week 0, 4, 13, 17, 52; SAD Cohorts: Weeks 0 & 4

Secondary Outcomes (10)

• Change in cartilage thickness in the medial femoro-tibial compartment of the target knee joint, assessed by MRI

  52 Weeks

• Change in total cartilage volume and thickness in the other compartments of the target knee joint, assessed by MRI

  52 Weeks

• Change over time of structural as well as compositional parameters of the knee joint (e.g. cartilage and bone), evaluated by MRI

  52 Weeks

• Change in WOMAC (Western Ontario MacMaster Osteoarthritis Questionaire) total score in the target knee from 5-point Likert scales

  52 Weeks

• Change in WOMAC Function and Pain index scores in the target knee

  52 Weeks

Study Arms (2)

AS902330

EXPERIMENTAL

Biological: AS902330

Placebo

PLACEBO COMPARATOR

Biological: AS902330

Interventions

AS902330 BIOLOGICAL

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.

Also known as: rhFGF 18, Recombinant human fibroblast growth factor 18, Sprifermin

AS902330; Placebo

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female \>= 40 years of age; females must be postmenopausal or surgically sterile
• 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)
• 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
• 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
• 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.
• 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
• Full understanding of the requirements of the study and willingness to comply with all study visits and assessments
• Patients must have read and understood the informed consent form, and must have signed it prior to any study-related procedure

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck KGaA, Darmstadt, Germany: lead

Study Sites (28)

UMHAT "Sv. Ivan Rilski", Clinical Research Unit for Phase I

Sofia, 1612, Bulgaria

Location

SKDS Research, Inc.

Newmarket, Canada

Location

Kells Medical Research Group

Pointe-Claire, Canada

Location

Centre de rhumatologie St-Louis

Québec, Canada

Location

Groupe de Recherche en Maldies Osseuses de Quebec

Québec, Canada

Location

London Road Diagnostic Clinic

Sarnia, Canada

Location

Albion Finch Medical Centre

Toronto, Canada

Location

Clinical hospital Split

Split, Croatia

Location

Clinical Hospital "Sestre Milosrdnice"

Zagreb, Croatia

Location

Polyclinic for internal medicine, gynecology, radiology, physical medicine and rehabilitation

Zagreb, Croatia

Location

Kuopio University Hospital, Department of Ortopaedics

Kuopio, Finland

Location

Oulu University Hospital, Surgical and Intensive Care Division

Oulu, Finland

Location

Turku University Central Hospital, Orthopedic Research Unit

Turku, Finland

Location

PAREXEL International GmbH

Berlin, 14050, Germany

Location

NZOZ Centrum Medyczne Artur Racewicz

Bialystok, Poland

Location

Krakowskie Centrum Medyczne NZOZ

Krakow, Poland

Location

REUMED Sp. z o.o.,

Lublin, Poland

Location

Niepubliczny Zaklad Opieki Zdrowotnej Nasz Lekarz

Torun, Poland

Location

Centrum Leczenia Chorob Cywilizacyjnych

Warsaw, Poland

Location

Centrum Medyczne OSTEOMED Sp. z o.o.

Warsaw, Poland

Location

Clinical Hospital Center Bezanijska Kosa

Belgrade, Serbia

Location

Institute of Rheumatology Resavska 69

Belgrade, Serbia

Location

• Name: Institute of diagnostic, prevention and rechabilitation of cardiovascular and rheumatoid diseases

Niška Banja, Serbia

Location

FARMOVS-PAREXEL (Pty) Ltd, University of the Free State

Bloemfontein, 9301, South Africa

Location

PAREXEL -George

George, 6529, South Africa

Location

PAREXEL-Port Elizabeth, Mercantile Hospital

Port Elizabeth, 6020, South Africa

Location

Ortopediska mottagningen

Hässleholm, Sweden

Location

Kirurg- och ortopedkliniken Kungälvs sjukhus, 442 83 Kungälv

Kungälv, Sweden

Location

Related Publications (4)

• Lohmander LS, Hellot S, Dreher D, Krantz EF, Kruger DS, Guermazi A, Eckstein F. Intraarticular sprifermin (recombinant human fibroblast growth factor 18) in knee osteoarthritis: a randomized, double-blind, placebo-controlled trial. Arthritis Rheumatol. 2014 Jul;66(7):1820-31. doi: 10.1002/art.38614.

  PMID: 24740822 RESULT

• Onuora S. Osteoarthritis: Sprifermin shows cartilage-protective effects in knee OA. Nat Rev Rheumatol. 2014 Jun;10(6):322. doi: 10.1038/nrrheum.2014.68. Epub 2014 May 6. No abstract available.

  PMID: 24798571 RESULT

• Roemer FW, Aydemir A, Lohmander S, Crema MD, Marra MD, Muurahainen N, Felson DT, Eckstein F, Guermazi A. Structural effects of sprifermin in knee osteoarthritis: a post-hoc analysis on cartilage and non-cartilaginous tissue alterations in a randomized controlled trial. BMC Musculoskelet Disord. 2016 Jul 9;17:267. doi: 10.1186/s12891-016-1128-2.

  PMID: 27393009 DERIVED

• Eckstein F, Wirth W, Guermazi A, Maschek S, Aydemir A. Brief report: intraarticular sprifermin not only increases cartilage thickness, but also reduces cartilage loss: location-independent post hoc analysis using magnetic resonance imaging. Arthritis Rheumatol. 2015 Nov;67(11):2916-22. doi: 10.1002/art.39265.

  PMID: 26138203 DERIVED

MeSH Terms

Conditions

Osteoarthritis, Knee

Interventions

fibroblast growth factor 18

Condition Hierarchy (Ancestors)

Osteoarthritis; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Study Officials

• Donatus Dreher, MD, PhD

  Merck Serono S.A., Geneva

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2009
• First Posted: December 17, 2009
• Study Start: October 1, 2008
• Primary Completion: October 1, 2010
• Study Completion: December 1, 2010
• Last Updated: June 25, 2014

Record last verified: 2014-06

Locations

BU (1); SE (2); CA (6); DE (1); ZA (3); FI (3); CR (3); PL (6)