A Locally Injected Bradykinin Antagonist for TReatment of OSteoarthritiS (ALBATROSS)
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| ClinicalTrials.gov Identifier: NCT01091116 |
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Recruitment Status :
Completed
First Posted : March 23, 2010
Results First Posted : February 18, 2013
Last Update Posted : February 18, 2013
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Osteoarthritis, Knee | Drug: MEN16132 - 0.125 mg Drug: MEN16132 - 0.25 mg Drug: MEN16132 - 0.5 mg Drug: Placebo | Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 423 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | 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 |
| Study Start Date : | March 2010 |
| Actual Primary Completion Date : | February 2011 |
| Actual Study Completion Date : | March 2011 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Double dose MEN16132 0.125 mg
Intra-articular administration of two 0.125 mg doses of MEN16132 at 2-week interval.
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Drug: MEN16132 - 0.125 mg
Intra-articular administration of two low doses of MEN16132 at 2-week interval.
Other Name: fasitibant 0.125 mg |
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Experimental: Double dose MEN16132 0.25 mg
Intra-articular administration of two 0.25 mg doses of MEN16132 at 2-week interval.
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Drug: MEN16132 - 0.25 mg
Intra-articular injection of two intermediate doses of MEN16132 at 2-week interval
Other Name: fasitibant 0.25 mg |
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Experimental: Double dose MEN16132 0.5 mg
Intra-articular administration of two 0.5 mg doses of MEN16132 at 2-week interval.
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Drug: MEN16132 - 0.5 mg
Intra-articular injection of two high doses of MEN16132 at 2-week interval
Other Name: fasitibant 0.5 mg |
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Experimental: 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.
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Drug: MEN16132 - 0.5 mg
Single intra-articular injection of one high dose of MEN16132, followed by one dose of placebo at 2-week interval
Other Name: fasitibant 0.5 mg |
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Placebo Comparator: Placebo
Intra-articular administration of two doses of Placebo at 2-week interval.
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Drug: Placebo
Intra-articular injection of 2 doses of Placebo control at 2-week interval |
- WOMAC VA 3.1 A Score (Total Pain) [ Time Frame: 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.
- WOMAC VA 3.1.B Score (Knee Stiffness) [ Time Frame: 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.
- WOMAC VA 3.1. C Score (Function) [ Time Frame: 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.
- Percentage of Treatment Responders According to OMERACT-OARSI Responder Criteria [ Time Frame: 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.
- Patient Global Assessment [ Time Frame: 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.
- WOMAC VA 3.1A - Total Pain Score by Body Mass Index [BMI <= 25] [ Time Frame: 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.
- WOMAC VA 3.1A - Total Pain Score by Body Mass Index -[BMI > 25] [ Time Frame: 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.
- Adverse Event Reports [ Time Frame: up to 4 months after screening ]Incidence of spontaneously reported adverse events
- Clinically Significant Abnormal Laboratory Tests [ Time Frame: 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.
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| Ages Eligible for Study: | 40 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01091116
Show 23 study locations
| Principal Investigator: | Karel Pavelka, Prof MD | Institute of Rheumatology, Charles University Prague |
| Responsible Party: | Menarini Group |
| ClinicalTrials.gov Identifier: | NCT01091116 |
| Other Study ID Numbers: |
BKOS-02 2009-014918-99 ( EudraCT Number ) |
| First Posted: | March 23, 2010 Key Record Dates |
| Results First Posted: | February 18, 2013 |
| Last Update Posted: | February 18, 2013 |
| Last Verified: | January 2013 |
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Injections, Intra-Articular |
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Osteoarthritis Osteoarthritis, Knee Arthritis Joint Diseases Musculoskeletal Diseases Rheumatic Diseases (4-amino-5-(4-(4-(2,4-dichloro-3-(2,4-dimethyl-8-quinolyloxymethyl)phenylsulfonamido)tetrahydro-2H-4-pyranoylcarbonyl)piperazino)-5-oxopentyl)(trimethyl)ammonium |
Bradykinin B2 Receptor Antagonists Bradykinin Receptor Antagonists Molecular Mechanisms of Pharmacological Action Complement Inactivating Agents Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs |