A Locally Injected Bradykinin Antagonist for TReatment of OSteoarthritiS

NCT01091116 | Completed Phase 2 Results

• 2 other identifiers: BKOS-022009-014918-99
• Study Type: interventional
• Target: 423
• Locations: 4 countries
• Sites: 23

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.

Conditions

Osteoarthritis, Knee

Keywords

Injections, Intra-Articular

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (8)

• WOMAC VA 3.1.B Score (Knee Stiffness)

  up to 3 months after first dose

• WOMAC VA 3.1. C Score (Function)

  up to 3 months after first dose

• Percentage of Treatment Responders According to OMERACT-OARSI Responder Criteria

  up to 3 months after first dose

• Patient Global Assessment

  up to 3 months after first dose

• WOMAC VA 3.1A - Total Pain Score by Body Mass Index [BMI <= 25]

  over the 3 weeks after the first administration

Study Arms (5)

Double dose MEN16132 0.125 mg

EXPERIMENTAL

Intra-articular administration of two 0.125 mg doses of MEN16132 at 2-week interval.

Drug: MEN16132 - 0.125 mg

Double dose MEN16132 0.25 mg

EXPERIMENTAL

Intra-articular administration of two 0.25 mg doses of MEN16132 at 2-week interval.

Drug: MEN16132 - 0.25 mg

Double dose MEN16132 0.5 mg

EXPERIMENTAL

Intra-articular administration of two 0.5 mg doses of MEN16132 at 2-week interval.

Drug: MEN16132 - 0.5 mg

Single dose MEN16132 0.5 mg

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

Intra-articular administration of two doses of Placebo at 2-week interval.

Drug: Placebo

Interventions

MEN16132 - 0.125 mg DRUG

Intra-articular administration of two low doses of MEN16132 at 2-week interval.

Also known as: fasitibant 0.125 mg

Double dose MEN16132 0.125 mg

MEN16132 - 0.25 mg DRUG

Intra-articular injection of two intermediate doses of MEN16132 at 2-week interval

Also known as: fasitibant 0.25 mg

Double dose MEN16132 0.25 mg

MEN16132 - 0.5 mg DRUG

Intra-articular injection of two high doses of MEN16132 at 2-week interval

Also known as: fasitibant 0.5 mg

Double dose MEN16132 0.5 mg

Placebo DRUG

Intra-articular injection of 2 doses of Placebo control at 2-week interval

Placebo

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Menarini Group: lead

Study Sites (23)

Centre Hospitalier Régional - Hôpital Porte Madeleine

Orléans, 45000, France

Location

Hôtel Dieu - GHU Ouest

Paris, 75181, France

Location

Department of Rheumatology, Purpan University Hospital

Toulouse, 31300, France

Location

Rheumatologie/Immunologie - Rheumazentrum, Krankenhaus Doberan

Bad Doberan, 18209, Germany

Location

Klinik für Rheumatologie und Klinische Immunologie, Charité - Campus Charité Mitte

Berlin, 10117, Germany

Location

Orthopädische Praxis Dr. Wagenitz

Berlin, 12247, Germany

Location

ClinPharm International, Prüfzentrum Bochum

Bochum, 44787, Germany

Location

ClinPharm International, Prüfzentrum Dresden

Dresden, 01067, Germany

Location

Medizinische Klinik 3, Universität Erlangen-Nürnberg

Erlangen, 91054, Germany

Location

ClinPharm Prüfzentrum Frankfurt / aM

Frankfurt, 60596, Germany

Location

ClinPharm Prüfzentrum Görlitz

Görlitz, 02826, Germany

Location

Clinical Research Hamburg

Hamburg, 22143, Germany

Location

Orthopädie Zentrum Altona

Hamburg, 22767, Germany

Location

ClinPharm International, Prüfzentrum Leipzig

Leipzig, 04103, Germany

Location

ClinPharm Prüfzentrum Magdeburg

Magdeburg, 39104, Germany

Location

Servizio di Reumatologia, Ospedale Privato Accreditato Nigrisoli

Bologna, 40138, Italy

Location

Dipartimento di Biomedicina - SOD Reumatologia - Azienda Ospedaliera Universitaria Careggi

Florence, 50139, Italy

Location

Dipartimento di Medicina Interna Azienda Ospedaliero Universitaria Pisana-Stabilimento di Santa Chiara Pisa

Pisa, 56126, Italy

Location

Istituto di Reumatologia, "Policlinico Le Scotte" Università degli Studi di Siena

Siena, 53100, Italy

Location

Servicio de Reumatologia, Hospital de Basurto

Bilbao, 48013, Spain

Location

Servicio de Reumatologia, Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Servicio de Reumatologia, Corporacio Sanitaria Parc Tauli, Hospital de Sabadell

Sabadell, 08208, Spain

Location

Servicio de Reumatologia, Hospital Universitario Virgen Macarena

Seville, 41009, Spain

Location

MeSH Terms

Conditions

Osteoarthritis, Knee

Interventions

(4-amino-5-(4-(4-(2,4-dichloro-3-(2,4-dimethyl-8-quinolyloxymethyl)phenylsulfonamido)tetrahydro-2H-4-pyranoylcarbonyl)piperazino)-5-oxopentyl)(trimethyl)ammonium

Condition Hierarchy (Ancestors)

Osteoarthritis; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Results Point of Contact

• Title: Clinical Research Director
• Organization: Menarini-Ricerche

+39-055-56809990

Study Officials

• Karel Pavelka, Prof MD

  Institute of Rheumatology, Charles University Prague

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 18, 2010
• First Posted: March 23, 2010
• Study Start: March 1, 2010
• Primary Completion: February 1, 2011
• Study Completion: March 1, 2011
• Last Updated: February 18, 2013
• Results First Posted: February 18, 2013

Record last verified: 2013-01

Locations

IT (4); DE (12); ES (4); FR (3)