Clinical trial NCT01091116: A Locally Injected Bradykinin Antagonist for TReatment of OSteoarthritiS
Official title: Intra-articular Treatment With MEN16132 in Patients With Symptomatic Primary Osteoarthritis of the Knee: A Randomized, Multi-centre, Double Blind, Placebo Controlled, Five Parallel Group, Dose Finding Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Osteoarthritis, Knee
Keywords: Injections, Intra-Articular
Lead sponsor: Menarini Group
Sponsor class: INDUSTRY
First posted: 2010-03-23
Enrollment: 423
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether intra-articular (knee joint) administration of MEN16132 is effective reducing the pain from knee osteoarthritis.

Detailed description: MEN16132 is a non-peptide bradykinin B2-receptor antagonist showing analgesic and anti-inflammatory activity in nonclinical osteoarthritis models. This study is being conducted as a dose finding study to determine the safety and efficacy of MEN16132, given as three doses/four treatment regimens in comparison to placebo, as well the time to onset and duration of effect.

Eligibility criteria: Main Inclusion Criteria:

* Male or female patients ≥40 years old.
* Symptomatic primary knee osteoarthritis (ACR criteria) since ≥6 months prior to screening, Kellgren Lawrence Grade 2 or 3, and representing an indication for intra-articular drug injection.
* \>50 mm VAS pain score assigned to the index knee at WOMAC VA 3.1-A1 (pain while walking on a flat surface).
* \>125 mm VAS pain score assigned to the index knee at WOMAC VA 3.1 A subscore (total pain).
* Pain in the index knee on at least 50% of the days in the month preceding the screening.

Main Exclusion Criteria:

* Patients with Kellgren \& Lawrence Grade I or IV (doubtful or severe) osteoarthritis of the knee.
* Knee condition representing an indication for surgery
* Patients with Inflammatory or crystal arthropathies, acute fractures, severe loss of bone density, bone necrosis.
* Patients with isolated patella-femoral syndrome or chondromalacia.
* Patients with OA predominant in the lateral compartment or any significant valgus deformity.
* Patients with any other disease or condition interfering with the free use and evaluation of the index knee for the 3 month duration of the trial (e.g. cancer, congenital defects, spine osteoarthritis).
* Major injury or surgery to the index knee within the previous 12 months prior to screening.
* Severe hip osteoarthritis ipsilateral to index knee.
* Any pain \>30 mm VAS that could interfere with the assessment of index knee pain (e.g. pain in any other part of the lower extremities, pain radiating to the knee).
* Any pharmacological or non-pharmacological treatment started or changed during 4 weeks prior to randomisation or likely to be changed during the duration of the study
* Use of systemic or topical corticosteroids \>10 mg prednisolone equivalent per day during 30 days prior to randomisation.
* Use of any pain or OA medication (e.g. NSAIDs, COX-2 inhibitors, analgesics) during 1 or 2 weeks prior to randomisation.
* Any intra-articular or local periarticular punction, injection or surgery to the index knee during the 6 months prior to screening.

Primary outcomes:
measure: WOMAC VA 3.1 A Score (Total Pain)
timeFrame: over the 3 weeks after the first administration
Secondary outcomes:
measure: WOMAC VA 3.1.B Score (Knee Stiffness)
timeFrame: up to 3 months after first dose
measure: WOMAC VA 3.1. C Score (Function)
timeFrame: up to 3 months after first dose
measure: Percentage of Treatment Responders According to OMERACT-OARSI Responder Criteria
timeFrame: up to 3 months after first dose
measure: Patient Global Assessment
timeFrame: up to 3 months after first dose
measure: WOMAC VA 3.1A - Total Pain Score by Body Mass Index [BMI <= 25]
timeFrame: over the 3 weeks after the first administration
measure: WOMAC VA 3.1A - Total Pain Score by Body Mass Index -[BMI > 25]
timeFrame: over the 3 weeks after the first administration
measure: Adverse Event Reports
timeFrame: up to 4 months after screening
measure: Clinically Significant Abnormal Laboratory Tests
timeFrame: up to 4 months from screening
Other outcomes:
Locations:
city: Orléans
country: France
facility: Centre Hospitalier Régional - Hôpital Porte Madeleine
city: Paris
country: France
facility: Hôtel Dieu - GHU Ouest
city: Toulouse
country: France
facility: Department of Rheumatology, Purpan University Hospital
city: Bad Doberan
country: Germany
facility: Rheumatologie/Immunologie - Rheumazentrum, Krankenhaus Doberan
city: Berlin
country: Germany
facility: Klinik für Rheumatologie und Klinische Immunologie, Charité - Campus Charité Mitte
city: Berlin
country: Germany
facility: Orthopädische Praxis Dr. Wagenitz
city: Bochum
country: Germany
facility: ClinPharm International, Prüfzentrum Bochum
city: Dresden
country: Germany
facility: ClinPharm International, Prüfzentrum Dresden
city: Erlangen
country: Germany
facility: Medizinische Klinik 3, Universität Erlangen-Nürnberg
city: Frankfurt
country: Germany
facility: ClinPharm Prüfzentrum Frankfurt / aM
city: Görlitz
country: Germany
facility: ClinPharm Prüfzentrum Görlitz
city: Hamburg
country: Germany
facility: Clinical Research Hamburg
city: Hamburg
country: Germany
facility: Orthopädie Zentrum Altona
city: Leipzig
country: Germany
facility: ClinPharm International, Prüfzentrum Leipzig
city: Magdeburg
country: Germany
facility: ClinPharm Prüfzentrum Magdeburg
city: Bologna
country: Italy
facility: Servizio di Reumatologia, Ospedale Privato Accreditato Nigrisoli
city: Firenze
country: Italy
facility: Dipartimento di Biomedicina - SOD Reumatologia - Azienda Ospedaliera Universitaria Careggi
city: Pisa
country: Italy
facility: Dipartimento di Medicina Interna Azienda Ospedaliero Universitaria Pisana-Stabilimento di Santa Chiara Pisa
city: Siena
country: Italy
facility: Istituto di Reumatologia, "Policlinico Le Scotte" Università degli Studi di Siena
city: Bilbao
country: Spain
facility: Servicio de Reumatologia, Hospital de Basurto
city: Madrid
country: Spain
facility: Servicio de Reumatologia, Hospital Universitario La Paz
city: Sabadell
country: Spain
facility: Servicio de Reumatologia, Corporacio Sanitaria Parc Tauli, Hospital de Sabadell
city: Sevilla
country: Spain
facility: Servicio de Reumatologia, Hospital Universitario Virgen Macarena
Study officials:
affiliation: Institute of Rheumatology, Charles University Prague
name: Karel Pavelka, Prof MD
role: PRINCIPAL_INVESTIGATOR
References: