A Locally Injected Bradykinin Antagonist for TReatment of OSteoarthritiS
- Conditions
- Osteoarthritis, Knee
- Interventions
- Drug: MEN16132 - 0.25 mgDrug: MEN16132 - 0.5 mgDrug: MEN16132 - 0.125 mgDrug: Placebo
- Registration Number
- NCT01091116
- Lead Sponsor
- Menarini Group
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 423
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Double dose MEN16132 0.25 mg MEN16132 - 0.25 mg Intra-articular administration of two 0.25 mg doses of MEN16132 at 2-week interval. Double dose MEN16132 0.5 mg MEN16132 - 0.5 mg Intra-articular administration of two 0.5 mg doses of MEN16132 at 2-week interval. Single dose MEN16132 0.5 mg MEN16132 - 0.5 mg Intra-articular administration of one 0.5 mg dose of MEN16132 followed by one intra-articular injection of placebo at 2-week interval. Double dose MEN16132 0.125 mg MEN16132 - 0.125 mg Intra-articular administration of two 0.125 mg doses of MEN16132 at 2-week interval. Placebo Placebo Intra-articular administration of two doses of Placebo at 2-week interval.
- Primary Outcome Measures
Name Time Method WOMAC VA 3.1 A Score (Total Pain) over the 3 weeks after the first administration Western Ontario and McMaster Universities osteoarthritis index (WOMAC). The WOMAC VA 3.1 A score (total pain , range 0-500 mm) is the sum of VAS scores (0-100 mm) attributed by the patient to each of the 5 questions referring to osteoarthritic pain experienced during the preceding 48 hours.
The higher is the WOMAC VA 3.1 A score, the higher is the intensity of pain symptoms (0 = no pain ; 500 = extreme pain).
A decrease of the WOMAC VA 3.1 A score following treatment administration indicates a reduction of pain symptom.
The change from baseline was assessed along 3 weeks after first drug administrations.
- Secondary Outcome Measures
Name Time Method WOMAC VA 3.1.B Score (Knee Stiffness) up to 3 months after first dose WOMAC VA 3.1.B score(range 0-200) is the sum of VAS scores (0-100 mm)attributed by the patient to each of the 2 questions referring to joint stiffness experienced during the preceding 48 hours. The higher is the WOMAC VA 3.1 B score, the higher is joint stiffness (0 = no stiffness ; 200 = extreme stiffness).
A decrease of the WOMAC VA 3.1 B score following treatment administration indicates a reduction of joint stiffness.
The change at Week 13 from baseline is reported.WOMAC VA 3.1. C Score (Function) up to 3 months after first dose Knee function evaluated by WOMAC VA 3.1 C score (range 0-1700) is the sum of VAS scores (range 0-100 mm) attributed by the patient to each of 17 questions referring to difficulty in performing daily activities experienced during the preceding 48 hours.
The higher is the WOMAC VA 3.1 C score, the higher is functional impairment in daily activities (0 = no difficulty ; 1700 = extreme difficulty).
A decrease of the WOMAC VA 3.1 C score following treatment administration indicates an improvement in performing daily activities.
WOMAC VA 3.1.C scores at baseline and at Week 13 are reported.Percentage of Treatment Responders According to OMERACT-OARSI Responder Criteria up to 3 months after first dose Osteoarthritis Research Society International (OARSI).
Response defined as:
* a decrease in WOMAC pain or physical-function score by 50% or more and by 20 or more points on the visual analogue scale
* OR if two of the following three findings are recorded:
a decrease in the WOMAC pain score by 20% or more and by 10 or more points on the visual analogue scale; a decrease in the WOMAC physical-function score by 20% or more and by 10 or more points on the scale; an improvement in the score on the patient's global assessment by 20% or more and by 10 or more points on the scale.Patient Global Assessment up to 3 months after first dose Patient global assessment evaluated using a VAS scale score attributed by the patient (range 0-100 mm).
Efficacy assessed as change at each time-point post-dosing (week 1, 2 ,3, 13) versus baseline (week 0).
A decrease of patient global assessment score indicates an improvement of osteoarthritis symptoms.WOMAC VA 3.1A - Total Pain Score by Body Mass Index [BMI <= 25] over the 3 weeks after the first administration Analysis in normal-weight population (BMI \<= 25) of the WOMAC VA 3.1A score (range 0-500 mm) is reported.
A decrease of the WOMAC VA 3.1 A score following treatment administration indicates a reduction of pain symptom.WOMAC VA 3.1A - Total Pain Score by Body Mass Index -[BMI > 25] over the 3 weeks after the first administration Analysis in over-weight population (BMI \> 25) of the WOMAC VA 3.1A score (range 0-500 mm) is reported.
A decrease of the WOMAC VA 3.1 A score following treatment administration indicates a reduction of pain symptom.Adverse Event Reports up to 4 months after screening Incidence of spontaneously reported adverse events
Clinically Significant Abnormal Laboratory Tests up to 4 months from screening Percentage of patients with Abnormal Laboratory Tests judged Clinically Significant by Investigators.
The following hematochemical and urinary parameters were analysed:
Red Blood Cells Count, Haematocrit, Haemoglobin, Platelets, MCV, MCH, MCHC, White Blood Cells, Sodium, Chloride, Potassium, Total calcium, AST (SGOT), ALT (SGPT), GGT, Alkaline phosphatase, Total Bilirubin, Direct Bilirubin, Creatinine, BUN, CPK, LDH, Glucose, Total proteins, Albumin.
Trial Locations
- Locations (23)
Department of Rheumatology, Purpan University Hospital
🇫🇷Toulouse, France
ClinPharm Prüfzentrum Frankfurt / aM
🇩🇪Frankfurt, Germany
Orthopädische Praxis Dr. Wagenitz
🇩🇪Berlin, Germany
Rheumatologie/Immunologie - Rheumazentrum, Krankenhaus Doberan
🇩🇪Bad Doberan, Germany
Hôtel Dieu - GHU Ouest
🇫🇷Paris, France
Servicio de Reumatologia, Hospital de Basurto
🇪🇸Bilbao, Spain
Centre Hospitalier Régional - Hôpital Porte Madeleine
🇫🇷Orléans, France
Orthopädie Zentrum Altona
🇩🇪Hamburg, Germany
Servicio de Reumatologia, Hospital Universitario La Paz
🇪🇸Madrid, Spain
Medizinische Klinik 3, Universität Erlangen-Nürnberg
🇩🇪Erlangen, Germany
ClinPharm International, Prüfzentrum Bochum
🇩🇪Bochum, Germany
ClinPharm International, Prüfzentrum Dresden
🇩🇪Dresden, Germany
Klinik für Rheumatologie und Klinische Immunologie, Charité - Campus Charité Mitte
🇩🇪Berlin, Germany
ClinPharm Prüfzentrum Görlitz
🇩🇪Görlitz, Germany
ClinPharm International, Prüfzentrum Leipzig
🇩🇪Leipzig, Germany
Clinical Research Hamburg
🇩🇪Hamburg, Germany
ClinPharm Prüfzentrum Magdeburg
🇩🇪Magdeburg, Germany
Istituto di Reumatologia, "Policlinico Le Scotte" Università degli Studi di Siena
🇮🇹Siena, Italy
Servizio di Reumatologia, Ospedale Privato Accreditato Nigrisoli
🇮🇹Bologna, Italy
Dipartimento di Biomedicina - SOD Reumatologia - Azienda Ospedaliera Universitaria Careggi
🇮🇹Firenze, Italy
Dipartimento di Medicina Interna Azienda Ospedaliero Universitaria Pisana-Stabilimento di Santa Chiara Pisa
🇮🇹Pisa, Italy
Servicio de Reumatologia, Corporacio Sanitaria Parc Tauli, Hospital de Sabadell
🇪🇸Sabadell, Spain
Servicio de Reumatologia, Hospital Universitario Virgen Macarena
🇪🇸Sevilla, Spain