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

16 januari 2013 uppdaterad av: Menarini Group

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

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

Studieöversikt

Status

Avslutad

Betingelser

Intervention / Behandling

Detaljerad beskrivning

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.

Studietyp

Interventionell

Inskrivning (Faktisk)

423

Fas

  • Fas 2

Kontakter och platser

Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.

Studieorter

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

Deltagandekriterier

Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.

Urvalskriterier

Åldrar som är berättigade till studier

40 år och äldre (Vuxen, Äldre vuxen)

Tar emot friska volontärer

Nej

Kön som är behöriga för studier

Allt

Beskrivning

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.

Studieplan

Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.

Hur är studien utformad?

Designdetaljer

  • Primärt syfte: Behandling
  • Tilldelning: Randomiserad
  • Interventionsmodell: Parallellt uppdrag
  • Maskning: Fyrdubbla

Vapen och interventioner

Deltagargrupp / Arm
Intervention / Behandling
Experimentell: Double dose MEN16132 0.125 mg
Intra-articular administration of two 0.125 mg doses of MEN16132 at 2-week interval.
Läkemedel: MEN16132 - 0.125 mg
Intra-articular administration of two low doses of MEN16132 at 2-week interval.
Andra namn:
  • fasitibant 0.125 mg
Experimentell: Double dose MEN16132 0.25 mg
Intra-articular administration of two 0.25 mg doses of MEN16132 at 2-week interval.
Läkemedel: MEN16132 - 0.25 mg
Intra-articular injection of two intermediate doses of MEN16132 at 2-week interval
Andra namn:
  • fasitibant 0.25 mg
Experimentell: Double dose MEN16132 0.5 mg
Intra-articular administration of two 0.5 mg doses of MEN16132 at 2-week interval.
Läkemedel: MEN16132 - 0.5 mg
Intra-articular injection of two high doses of MEN16132 at 2-week interval
Andra namn:
  • fasitibant 0.5 mg
Läkemedel: MEN16132 - 0.5 mg
Single intra-articular injection of one high dose of MEN16132, followed by one dose of placebo at 2-week interval
Andra namn:
  • fasitibant 0.5 mg
Experimentell: 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.
Läkemedel: MEN16132 - 0.5 mg
Intra-articular injection of two high doses of MEN16132 at 2-week interval
Andra namn:
  • fasitibant 0.5 mg
Läkemedel: MEN16132 - 0.5 mg
Single intra-articular injection of one high dose of MEN16132, followed by one dose of placebo at 2-week interval
Andra namn:
  • fasitibant 0.5 mg
Placebo-jämförare: Placebo
Intra-articular administration of two doses of Placebo at 2-week interval.
Läkemedel: Placebo
Intra-articular injection of 2 doses of Placebo control at 2-week interval

Vad mäter studien?

Primära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
WOMAC VA 3.1 A Score (Total Pain)
Tidsram: 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.
over the 3 weeks after the first administration

Sekundära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
WOMAC VA 3.1.B Score (Knee Stiffness)
Tidsram: 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.
up to 3 months after first dose
WOMAC VA 3.1. C Score (Function)
Tidsram: 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.
up to 3 months after first dose
Percentage of Treatment Responders According to OMERACT-OARSI Responder Criteria
Tidsram: 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.
up to 3 months after first dose
Patient Global Assessment
Tidsram: 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.
up to 3 months after first dose
WOMAC VA 3.1A - Total Pain Score by Body Mass Index [BMI <= 25]
Tidsram: 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.
over the 3 weeks after the first administration
WOMAC VA 3.1A - Total Pain Score by Body Mass Index -[BMI > 25]
Tidsram: 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.
over the 3 weeks after the first administration
Adverse Event Reports
Tidsram: up to 4 months after screening
Incidence of spontaneously reported adverse events
up to 4 months after screening
Clinically Significant Abnormal Laboratory Tests
Tidsram: 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.
up to 4 months from screening

Samarbetspartners och utredare

Det är här du hittar personer och organisationer som är involverade i denna studie.

Sponsor

Menarini Group

Utredare

  • Huvudutredare: Karel Pavelka, Prof MD, Institute of Rheumatology, Charles University Prague

Studieavstämningsdatum

Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.

Studera stora datum

Studiestart

1 mars 2010

Primärt slutförande (Faktisk)

1 februari 2011

Avslutad studie (Faktisk)

1 mars 2011

Studieregistreringsdatum

Först inskickad

18 mars 2010

Först inskickad som uppfyllde QC-kriterierna

19 mars 2010

Första postat (Uppskatta)

23 mars 2010

Uppdateringar av studier

Senaste uppdatering publicerad (Uppskatta)

18 februari 2013

Senaste inskickade uppdateringen som uppfyllde QC-kriterierna

16 januari 2013

Senast verifierad

1 januari 2013

Mer information

Termer relaterade till denna studie

Nyckelord

Ytterligare relevanta MeSH-villkor

Andra studie-ID-nummer

  • BKOS-02
  • 2009-014918-99 (EudraCT-nummer)

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