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

Menarini

Status and phase: Completed; Phase 2

Conditions: Osteoarthritis, Knee

Treatments: Drug: MEN16132 - 0.5 mg; Drug: MEN16132 - 0.25 mg; Drug: MEN16132 - 0.125 mg; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT01091116

BKOS-02

2009-014918-99 (EudraCT Number)

Details and patient eligibility

About

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

Full 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.

Enrollment: 423 patients

Sex: All

Ages: 40+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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423 participants in 5 patient groups, including a placebo group

Double dose MEN16132 0.125 mg

Experimental group

Description:

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

Treatment:

Drug: MEN16132 - 0.125 mg

Double dose MEN16132 0.25 mg

Experimental group

Description:

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

Treatment:

Drug: MEN16132 - 0.25 mg

Double dose MEN16132 0.5 mg

Experimental group

Description:

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

Treatment:

Drug: MEN16132 - 0.5 mg

Drug: MEN16132 - 0.5 mg

Single dose MEN16132 0.5 mg

Experimental group

Description:

Intra-articular administration of one 0.5 mg dose of MEN16132 followed by one intra-articular injection of placebo at 2-week interval.

Treatment:

Drug: MEN16132 - 0.5 mg

Drug: MEN16132 - 0.5 mg

Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo