A Locally Injected Bradykinin Antagonist for TReatment of OSteoarthritiS

Osteoarthritis, Knee Clinical Trial

— ALBATROSS  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01091116
• Other study ID #: BKOS-02
• Secondary ID: 2009-014918-99
• Status: Completed
• Phase: Phase 2
• First received: March 18, 2010
• Last updated: January 16, 2013
• Start date: March 2010
• Est. completion date: March 2011

Study information

• Verified date: January 2013
• Source: Menarini Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Germany: Federal Institute for Drugs and Medical DevicesItaly: Ethics CommitteeSpain: Agencia Española de Medicamentos y Productos SanitariosUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 423
• Est. completion date: March 2011
• Est. primary completion date: February 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Osteoarthritis
• Osteoarthritis, Knee

Intervention

Drug:
• MEN16132 - 0.125 mg
Intra-articular administration of two low doses of MEN16132 at 2-week interval.
• MEN16132 - 0.25 mg
Intra-articular injection of two intermediate doses of MEN16132 at 2-week interval
• MEN16132 - 0.5 mg
Intra-articular injection of two high doses of MEN16132 at 2-week interval
• MEN16132 - 0.5 mg
Single intra-articular injection of one high dose of MEN16132, followed by one dose of placebo at 2-week interval
• Placebo
Intra-articular injection of 2 doses of Placebo control at 2-week interval

Locations

Country	Name	City	State
France	Centre Hospitalier Régional - Hôpital Porte Madeleine	Orléans
France	Hôtel Dieu - GHU Ouest	Paris
France	Department of Rheumatology, Purpan University Hospital	Toulouse
Germany	Rheumatologie/Immunologie - Rheumazentrum, Krankenhaus Doberan	Bad Doberan
Germany	Klinik für Rheumatologie und Klinische Immunologie, Charité - Campus Charité Mitte	Berlin
Germany	Orthopädische Praxis Dr. Wagenitz	Berlin
Germany	ClinPharm International, Prüfzentrum Bochum	Bochum
Germany	ClinPharm International, Prüfzentrum Dresden	Dresden
Germany	Medizinische Klinik 3, Universität Erlangen-Nürnberg	Erlangen
Germany	ClinPharm Prüfzentrum Frankfurt / aM	Frankfurt
Germany	ClinPharm Prüfzentrum Görlitz	Görlitz
Germany	Clinical Research Hamburg	Hamburg
Germany	Orthopädie Zentrum Altona	Hamburg
Germany	ClinPharm International, Prüfzentrum Leipzig	Leipzig
Germany	ClinPharm Prüfzentrum Magdeburg	Magdeburg
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	Istituto di Reumatologia, "Policlinico Le Scotte" Università degli Studi di Siena	Siena
Spain	Servicio de Reumatologia, Hospital de Basurto	Bilbao
Spain	Servicio de Reumatologia, Hospital Universitario La Paz	Madrid
Spain	Servicio de Reumatologia, Corporacio Sanitaria Parc Tauli, Hospital de Sabadell	Sabadell
Spain	Servicio de Reumatologia, Hospital Universitario Virgen Macarena	Sevilla

Sponsors (1)

Lead Sponsor	Collaborator
Menarini Group

Countries where clinical trial is conducted

France,  Germany,  Italy,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	WOMAC VA 3.1 A Score (Total Pain)	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.	over the 3 weeks after the first administration	No
Secondary	WOMAC VA 3.1.B Score (Knee Stiffness)	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.	up to 3 months after first dose	No
Secondary	WOMAC VA 3.1. C Score (Function)	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.	up to 3 months after first dose	No
Secondary	Percentage of Treatment Responders According to OMERACT-OARSI Responder Criteria	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.	up to 3 months after first dose	No
Secondary	Patient Global Assessment	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.	up to 3 months after first dose	No
Secondary	WOMAC VA 3.1A - Total Pain Score by Body Mass Index [BMI <= 25]	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.	over the 3 weeks after the first administration	No
Secondary	WOMAC VA 3.1A - Total Pain Score by Body Mass Index -[BMI > 25]	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.	over the 3 weeks after the first administration	No
Secondary	Adverse Event Reports	Incidence of spontaneously reported adverse events	up to 4 months after screening	Yes
Secondary	Clinically Significant Abnormal Laboratory Tests	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.	up to 4 months from screening	Yes