Intra-articular treatment with MEN16132 in patients with symptomatic primary osteoarthritis of the knee: A randomised, multicentre, double blind, placebo controlled, five parallel group, dose finding study - ALBATROSS - A Locally injected Bradykinin Antagonist for TReatment of OSteoarthritiS

• Conditions: symptomatic primary osteoarthritis of the knee; MedDRA version: 12.1Level: LLTClassification code 10031161Term: Osteoarthritis

• Registration Number: EUCTR2009-014918-99-IT
• Lead Sponsor: MENARINI RICERCHE S.P.A.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-11-17
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 400

Inclusion Criteria

1. Written informed consent. 2. Male or female patients ≥40 years old. 3. Women of childbearing potential are eligible to participate in the study if their pregnancy test (serum ?-hCG) is negative at screening, they are not nursing, and they use an effective method of contraception until all follow-up procedures are complete. Methods of contraception considered effective include oral, injectable or implanted hormonal contraceptive agents, hormone containing intra-uterine devices with failure rates <1% per year. 4. Symptomatic primary knee osteoarthritis (ACR criteria) since ≥6 months prior to screening, with documented minimal to moderate radiological severity (i.e. Kellgren Lawrence Grade 2 or 3) based on X-ray not older than 6 months, and representing an indication for intra-articular drug injection. 5. >50 mm VAS pain score assigned to the index knee at WOMAC VA 3.1-A1 (pain while walking on a flat surface). 6. >125 mm VAS pain score assigned to the index knee at WOMAC VA 3.1 A subscore (total pain). 7. Pain in the index knee on at least 50% of the days in the month preceding the screening. 8. Minimum flexion of 90 degrees in both knees. 9. Ability to perform the 15 m walk test without the support of crutches or other assistive devices. 10. Willingness to discontinue all pain or OA medication (e.g. NSAIDs, COX-2 inhibitors, analgesics) prior to randomisation and for the entire course of the study with a minimum wash-out of 1 or 2 weeks for drugs with short (i.e. < 5 hours) or longer half-life, respectively. NOTE: This does not include paracetamol, up to 1000 mg/day, as rescue medication and low dose aspirin for cardioprotection, up to 100 mg/day or other salicilates at equivalent doses. 11. Willingness to refrain from paracetamol use 48 hours prior to any study visit.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1 Inability to personally provide written informed consent 2 Inability to understand or collaborate throughout the study 3 Subjects who participated in another clinical trial within 30 days prior randomisation 4 Patients with Kellgren & Lawrence Grade I or IV osteoarthritis of the knee 5 Knee condition representing an indication for surgery 6 Inflammatory or crystal arthropathies 7 Patients with acute fractures, severe loss of bone density, bone necrosis 8 Patients with isolated patella-femoral syndrome or chondromalacia 9 Patients with OA predominant in the lateral compartment or any significant valgus deformity 10 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 11 Major injury or surgery to the index knee within the previous 12 months prior to screening 12 Severe hip osteoarthritis ipsilateral to index knee 13 Any pain >30 mm VAS that could interfere with the assessment of index knee pain 14 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. Stable treatment for stable chronic disease is permitted as is the use of oral contraception or hormone replacement therapy IF patients are expected to remain on constant doses throughout the course of the study 15 Use of systemic or topical corticosteroids >10 mg prednisolone equivalent per day during 30 days prior to randomisation 16 Use of any pain or OA medication during 1 or 2 weeks prior to randomisation for drugs with short or longer half-life, respectively 17 Any acute or newly diagnosed disease/condition requiring treatment 18 Any chronic disease/condition requiring treatment modification 19 History of hypersensitivity/allergy to drugs including paracetamol 20 Patients with any clinically significant abnormal diagnostic test result that may represent a health risk, impact the study or affect the patient`s ability to complete the study 21 Patients with liver disease 22 Patients with severe renal insufficiency 23 Any sign of significant inflammation or infection 24 Any skin disorder or infection overlying the index knee 25 Previous infection of the index knee 26 Any intra-articular or local peri-articular punction, injection or surgery to the index knee during the 6 months prior to screening 27 Patients with bleeding diathesis or on therapy with anticoagulants 28 Significant peri-articular calcification 29 Previous ligament reconstruction at the index knee

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the efficacy of MEN16132 given by intra-articular injections as four different doses/regimens versus placebo;Primary end point(s): The primary end-point to be tested on the intention to treat (ITT) population will be WOMAC VA 3.1 A subscore decrease over the 3 weeks after the first administration (Visits 3, 4 and 5) compared with baseline (Visit 2).;Secondary Objective: To evaluate the dose-effect relationship of MEN16132 to support the choice of the dose/schedule to be studied in the subsequent clinical phase III study; the time to onset and the duration of effect; the safety and tolerability of MEN16132 given as 1 mL solution for intra-articular injection up to 0.5 mg dose for a cumulative dose up to 1.0 mg; the population pharmacokinetics of MEN16132 in patients