A Locally Injected Bradykinin Antagonist for TReatment of OSteoarthritiS (ALBATROSS)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Menarini Group
ClinicalTrials.gov Identifier:
NCT01091116
First received: March 18, 2010
Last updated: January 16, 2013
Last verified: January 2013
  Purpose

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


Condition Intervention Phase
Osteoarthritis, Knee
Drug: MEN16132 - 0.125 mg
Drug: MEN16132 - 0.25 mg
Drug: MEN16132 - 0.5 mg
Drug: Placebo
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Menarini Group:

Primary Outcome Measures:
  • WOMAC VA 3.1 A Score (Total Pain) [ Time Frame: over the 3 weeks after the first administration ] [ Designated as safety issue: No ]

    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:
  • WOMAC VA 3.1.B Score (Knee Stiffness) [ Time Frame: up to 3 months after first dose ] [ Designated as safety issue: No ]

    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) [ Time Frame: up to 3 months after first dose ] [ Designated as safety issue: No ]

    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 [ Time Frame: up to 3 months after first dose ] [ Designated as safety issue: No ]

    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 [ Time Frame: up to 3 months after first dose ] [ Designated as safety issue: No ]

    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] [ Time Frame: over the 3 weeks after the first administration ] [ Designated as safety issue: No ]

    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] [ Time Frame: over the 3 weeks after the first administration ] [ Designated as safety issue: No ]

    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 [ Time Frame: up to 4 months after screening ] [ Designated as safety issue: Yes ]
    Incidence of spontaneously reported adverse events

  • Clinically Significant Abnormal Laboratory Tests [ Time Frame: up to 4 months from screening ] [ Designated as safety issue: Yes ]

    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.



Enrollment: 423
Study Start Date: March 2010
Study Completion Date: March 2011
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Double dose MEN16132 0.125 mg
Intra-articular administration of two 0.125 mg doses of MEN16132 at 2-week interval.
Drug: MEN16132 - 0.125 mg
Intra-articular administration of two low doses of MEN16132 at 2-week interval.
Other Name: fasitibant 0.125 mg
Experimental: Double dose MEN16132 0.25 mg
Intra-articular administration of two 0.25 mg doses of MEN16132 at 2-week interval.
Drug: MEN16132 - 0.25 mg
Intra-articular injection of two intermediate doses of MEN16132 at 2-week interval
Other Name: fasitibant 0.25 mg
Experimental: Double dose MEN16132 0.5 mg
Intra-articular administration of two 0.5 mg doses of MEN16132 at 2-week interval.
Drug: MEN16132 - 0.5 mg
Intra-articular injection of two high doses of MEN16132 at 2-week interval
Other Name: fasitibant 0.5 mg
Experimental: Single dose 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.
Drug: MEN16132 - 0.5 mg
Single intra-articular injection of one high dose of MEN16132, followed by one dose of placebo at 2-week interval
Other Name: fasitibant 0.5 mg
Placebo Comparator: Placebo
Intra-articular administration of two doses of Placebo at 2-week interval.
Drug: Placebo
Intra-articular injection of 2 doses of Placebo control at 2-week interval

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

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01091116

Locations
France
Centre Hospitalier Régional - Hôpital Porte Madeleine
Orléans, France, 45000
Hôtel Dieu - GHU Ouest
Paris, France, 75181
Department of Rheumatology, Purpan University Hospital
Toulouse, France, 31300
Germany
Rheumatologie/Immunologie - Rheumazentrum, Krankenhaus Doberan
Bad Doberan, Germany, 18209
Klinik für Rheumatologie und Klinische Immunologie, Charité - Campus Charité Mitte
Berlin, Germany, 10117
Orthopädische Praxis Dr. Wagenitz
Berlin, Germany, 12247
ClinPharm International, Prüfzentrum Bochum
Bochum, Germany, 44787
ClinPharm International, Prüfzentrum Dresden
Dresden, Germany, 01067
Medizinische Klinik 3, Universität Erlangen-Nürnberg
Erlangen, Germany, 91054
ClinPharm Prüfzentrum Frankfurt / aM
Frankfurt, Germany, 60596
ClinPharm Prüfzentrum Görlitz
Görlitz, Germany, 02826
Clinical Research Hamburg
Hamburg, Germany, 22143
Orthopädie Zentrum Altona
Hamburg, Germany, 22767
ClinPharm International, Prüfzentrum Leipzig
Leipzig, Germany, 04103
ClinPharm Prüfzentrum Magdeburg
Magdeburg, Germany, 39104
Italy
Servizio di Reumatologia, Ospedale Privato Accreditato Nigrisoli
Bologna, Italy, 40138
Dipartimento di Biomedicina - SOD Reumatologia - Azienda Ospedaliera Universitaria Careggi
Firenze, Italy, 50139
Dipartimento di Medicina Interna Azienda Ospedaliero Universitaria Pisana-Stabilimento di Santa Chiara Pisa
Pisa, Italy, 56126
Istituto di Reumatologia, "Policlinico Le Scotte" Università degli Studi di Siena
Siena, Italy, 53100
Spain
Servicio de Reumatologia, Hospital de Basurto
Bilbao, Spain, 48013
Servicio de Reumatologia, Hospital Universitario La Paz
Madrid, Spain, 28046
Servicio de Reumatologia, Corporacio Sanitaria Parc Tauli, Hospital de Sabadell
Sabadell, Spain, 08208
Servicio de Reumatologia, Hospital Universitario Virgen Macarena
Sevilla, Spain, 41009
Sponsors and Collaborators
Menarini Group
Investigators
Principal Investigator: Karel Pavelka, Prof MD Institute of Rheumatology, Charles University Prague
  More Information

No publications provided

Responsible Party: Menarini Group
ClinicalTrials.gov Identifier: NCT01091116     History of Changes
Other Study ID Numbers: BKOS-02, 2009-014918-99
Study First Received: March 18, 2010
Results First Received: November 8, 2012
Last Updated: January 16, 2013
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Italy: Ethics Committee
Spain: Agencia Española de Medicamentos y Productos Sanitarios
United States: Food and Drug Administration

Keywords provided by Menarini Group:
Injections, Intra-Articular

Additional relevant MeSH terms:
Osteoarthritis
Osteoarthritis, Knee
Arthritis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases

ClinicalTrials.gov processed this record on April 17, 2014