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

16. januar 2013 oppdatert 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.

Studieoversikt

Status

Fullført

Forhold

Intervensjon / Behandling

Detaljert beskrivelse

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.

Studietype

Intervensjonell

Registrering (Faktiske)

423

Fase

  • Fase 2

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiesteder

  • 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
  • Italia
      • Bologna, Italia, 40138
        • Servizio di Reumatologia, Ospedale Privato Accreditato Nigrisoli
      • Firenze, Italia, 50139
        • Dipartimento di Biomedicina - SOD Reumatologia - Azienda Ospedaliera Universitaria Careggi
      • Pisa, Italia, 56126
        • Dipartimento di Medicina Interna Azienda Ospedaliero Universitaria Pisana-Stabilimento di Santa Chiara Pisa
      • Siena, Italia, 53100
        • Istituto di Reumatologia, "Policlinico Le Scotte" Università degli Studi di Siena
  • Spania
      • Bilbao, Spania, 48013
        • Servicio de Reumatologia, Hospital de Basurto
      • Madrid, Spania, 28046
        • Servicio de Reumatologia, Hospital Universitario La Paz
      • Sabadell, Spania, 08208
        • Servicio de Reumatologia, Corporacio Sanitaria Parc Tauli, Hospital de Sabadell
      • Sevilla, Spania, 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

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

40 år og eldre (Voksen, Eldre voksen)

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

Alle

Beskrivelse

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

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Tildeling: Randomisert
  • Intervensjonsmodell: Parallell tildeling
  • Masking: Firemannsrom

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Eksperimentell: Double dose MEN16132 0.125 mg
Intra-articular administration of two 0.125 mg doses of MEN16132 at 2-week interval.
Legemiddel: MEN16132 - 0.125 mg
Intra-articular administration of two low doses of MEN16132 at 2-week interval.
Andre navn:
  • fasitibant 0.125 mg
Eksperimentell: Double dose MEN16132 0.25 mg
Intra-articular administration of two 0.25 mg doses of MEN16132 at 2-week interval.
Legemiddel: MEN16132 - 0.25 mg
Intra-articular injection of two intermediate doses of MEN16132 at 2-week interval
Andre navn:
  • fasitibant 0.25 mg
Eksperimentell: Double dose MEN16132 0.5 mg
Intra-articular administration of two 0.5 mg doses of MEN16132 at 2-week interval.
Legemiddel: MEN16132 - 0.5 mg
Intra-articular injection of two high doses of MEN16132 at 2-week interval
Andre navn:
  • fasitibant 0.5 mg
Legemiddel: MEN16132 - 0.5 mg
Single intra-articular injection of one high dose of MEN16132, followed by one dose of placebo at 2-week interval
Andre navn:
  • fasitibant 0.5 mg
Eksperimentell: 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.
Legemiddel: MEN16132 - 0.5 mg
Intra-articular injection of two high doses of MEN16132 at 2-week interval
Andre navn:
  • fasitibant 0.5 mg
Legemiddel: MEN16132 - 0.5 mg
Single intra-articular injection of one high dose of MEN16132, followed by one dose of placebo at 2-week interval
Andre navn:
  • fasitibant 0.5 mg
Placebo komparator: Placebo
Intra-articular administration of two doses of Placebo at 2-week interval.
Legemiddel: Placebo
Intra-articular injection of 2 doses of Placebo control at 2-week interval

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
WOMAC VA 3.1 A Score (Total Pain)
Tidsramme: 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

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
WOMAC VA 3.1.B Score (Knee Stiffness)
Tidsramme: 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)
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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]
Tidsramme: 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]
Tidsramme: 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
Tidsramme: up to 4 months after screening
Incidence of spontaneously reported adverse events
up to 4 months after screening
Clinically Significant Abnormal Laboratory Tests
Tidsramme: 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

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

Menarini Group

Etterforskere

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

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart

1. mars 2010

Primær fullføring (Faktiske)

1. februar 2011

Studiet fullført (Faktiske)

1. mars 2011

Datoer for studieregistrering

Først innsendt

18. mars 2010

Først innsendt som oppfylte QC-kriteriene

19. mars 2010

Først lagt ut (Anslag)

23. mars 2010

Oppdateringer av studieposter

Sist oppdatering lagt ut (Anslag)

18. februar 2013

Siste oppdatering sendt inn som oppfylte QC-kriteriene

16. januar 2013

Sist bekreftet

1. januar 2013

Mer informasjon

Begreper knyttet til denne studien

Nøkkelord

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

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

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