Back to resultsA Locally Injected Bradykinin Antagonist for TReatment of OSteoarthritiS (ALBATROSS)
Primary Purpose
Osteoarthritis, Knee
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
MEN16132 - 0.125 mg
MEN16132 - 0.25 mg
MEN16132 - 0.5 mg
MEN16132 - 0.5 mg
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Osteoarthritis, Knee focused on measuring Injections, Intra-Articular
Eligibility 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.
Sites / Locations
- Centre Hospitalier Régional - Hôpital Porte Madeleine
- Hôtel Dieu - GHU Ouest
- Department of Rheumatology, Purpan University Hospital
- Rheumatologie/Immunologie - Rheumazentrum, Krankenhaus Doberan
- Klinik für Rheumatologie und Klinische Immunologie, Charité - Campus Charité Mitte
- Orthopädische Praxis Dr. Wagenitz
- ClinPharm International, Prüfzentrum Bochum
- ClinPharm International, Prüfzentrum Dresden
- Medizinische Klinik 3, Universität Erlangen-Nürnberg
- ClinPharm Prüfzentrum Frankfurt / aM
- ClinPharm Prüfzentrum Görlitz
- Clinical Research Hamburg
- Orthopädie Zentrum Altona
- ClinPharm International, Prüfzentrum Leipzig
- ClinPharm Prüfzentrum Magdeburg
- Servizio di Reumatologia, Ospedale Privato Accreditato Nigrisoli
- Dipartimento di Biomedicina - SOD Reumatologia - Azienda Ospedaliera Universitaria Careggi
- Dipartimento di Medicina Interna Azienda Ospedaliero Universitaria Pisana-Stabilimento di Santa Chiara Pisa
- Istituto di Reumatologia, "Policlinico Le Scotte" Università degli Studi di Siena
- Servicio de Reumatologia, Hospital de Basurto
- Servicio de Reumatologia, Hospital Universitario La Paz
- Servicio de Reumatologia, Corporacio Sanitaria Parc Tauli, Hospital de Sabadell
- Servicio de Reumatologia, Hospital Universitario Virgen Macarena
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Experimental
Experimental
Experimental
Experimental
Placebo Comparator
Arm Label
Double dose MEN16132 0.125 mg
Double dose MEN16132 0.25 mg
Double dose MEN16132 0.5 mg
Single dose MEN16132 0.5 mg
Placebo
Arm Description
Intra-articular administration of two 0.125 mg doses of MEN16132 at 2-week interval.
Intra-articular administration of two 0.25 mg doses of MEN16132 at 2-week interval.
Intra-articular administration of two 0.5 mg doses of MEN16132 at 2-week interval.
Intra-articular administration of one 0.5 mg dose of MEN16132 followed by one intra-articular injection of placebo at 2-week interval.
Intra-articular administration of two doses of Placebo at 2-week interval.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
WOMAC VA 3.1.B Score (Knee Stiffness)
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)
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
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
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]
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]
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
Incidence of spontaneously reported adverse events
Clinically Significant Abnormal Laboratory Tests
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01091116
Brief Title
A Locally Injected Bradykinin Antagonist for TReatment of OSteoarthritiS
Acronym
ALBATROSS
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 Type
Interventional
2. Study Status
Record Verification Date
January 2013
Overall Recruitment Status
Completed
Study Start Date
March 2010 (undefined)
Primary Completion Date
February 2011 (Actual)
Study Completion Date
March 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Menarini Group
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
Detailed 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Osteoarthritis, Knee
Keywords
Injections, Intra-Articular
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
423 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Double dose MEN16132 0.125 mg
Arm Type
Experimental
Arm Description
Intra-articular administration of two 0.125 mg doses of MEN16132 at 2-week interval.
Arm Title
Double dose MEN16132 0.25 mg
Arm Type
Experimental
Arm Description
Intra-articular administration of two 0.25 mg doses of MEN16132 at 2-week interval.
Arm Title
Double dose MEN16132 0.5 mg
Arm Type
Experimental
Arm Description
Intra-articular administration of two 0.5 mg doses of MEN16132 at 2-week interval.
Arm Title
Single dose MEN16132 0.5 mg
Arm Type
Experimental
Arm Description
Intra-articular administration of one 0.5 mg dose of MEN16132 followed by one intra-articular injection of placebo at 2-week interval.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Intra-articular administration of two doses of Placebo at 2-week interval.
Intervention Type
Drug
Intervention Name(s)
MEN16132 - 0.125 mg
Other Intervention Name(s)
fasitibant 0.125 mg
Intervention Description
Intra-articular administration of two low doses of MEN16132 at 2-week interval.
Intervention Type
Drug
Intervention Name(s)
MEN16132 - 0.25 mg
Other Intervention Name(s)
fasitibant 0.25 mg
Intervention Description
Intra-articular injection of two intermediate doses of MEN16132 at 2-week interval
Intervention Type
Drug
Intervention Name(s)
MEN16132 - 0.5 mg
Other Intervention Name(s)
fasitibant 0.5 mg
Intervention Description
Intra-articular injection of two high doses of MEN16132 at 2-week interval
Intervention Type
Drug
Intervention Name(s)
MEN16132 - 0.5 mg
Other Intervention Name(s)
fasitibant 0.5 mg
Intervention Description
Single intra-articular injection of one high dose of MEN16132, followed by one dose of placebo at 2-week interval
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Intra-articular injection of 2 doses of Placebo control at 2-week interval
Primary Outcome Measure Information:
Title
WOMAC VA 3.1 A Score (Total Pain)
Description
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.
Time Frame
over the 3 weeks after the first administration
Secondary Outcome Measure Information:
Title
WOMAC VA 3.1.B Score (Knee Stiffness)
Description
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.
Time Frame
up to 3 months after first dose
Title
WOMAC VA 3.1. C Score (Function)
Description
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.
Time Frame
up to 3 months after first dose
Title
Percentage of Treatment Responders According to OMERACT-OARSI Responder Criteria
Description
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.
Time Frame
up to 3 months after first dose
Title
Patient Global Assessment
Description
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.
Time Frame
up to 3 months after first dose
Title
WOMAC VA 3.1A - Total Pain Score by Body Mass Index [BMI <= 25]
Description
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.
Time Frame
over the 3 weeks after the first administration
Title
WOMAC VA 3.1A - Total Pain Score by Body Mass Index -[BMI > 25]
Description
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.
Time Frame
over the 3 weeks after the first administration
Title
Adverse Event Reports
Description
Incidence of spontaneously reported adverse events
Time Frame
up to 4 months after screening
Title
Clinically Significant Abnormal Laboratory Tests
Description
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.
Time Frame
up to 4 months from screening
10. Eligibility
Sex
All
Minimum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Karel Pavelka, Prof MD
Organizational Affiliation
Institute of Rheumatology, Charles University Prague
Official's Role
Principal Investigator
Facility Information:
Facility Name
Centre Hospitalier Régional - Hôpital Porte Madeleine
City
Orléans
ZIP/Postal Code
45000
Country
France
Facility Name
Hôtel Dieu - GHU Ouest
City
Paris
ZIP/Postal Code
75181
Country
France
Facility Name
Department of Rheumatology, Purpan University Hospital
City
Toulouse
ZIP/Postal Code
31300
Country
France
Facility Name
Rheumatologie/Immunologie - Rheumazentrum, Krankenhaus Doberan
City
Bad Doberan
ZIP/Postal Code
18209
Country
Germany
Facility Name
Klinik für Rheumatologie und Klinische Immunologie, Charité - Campus Charité Mitte
City
Berlin
ZIP/Postal Code
10117
Country
Germany
Facility Name
Orthopädische Praxis Dr. Wagenitz
City
Berlin
ZIP/Postal Code
12247
Country
Germany
Facility Name
ClinPharm International, Prüfzentrum Bochum
City
Bochum
ZIP/Postal Code
44787
Country
Germany
Facility Name
ClinPharm International, Prüfzentrum Dresden
City
Dresden
ZIP/Postal Code
01067
Country
Germany
Facility Name
Medizinische Klinik 3, Universität Erlangen-Nürnberg
City
Erlangen
ZIP/Postal Code
91054
Country
Germany
Facility Name
ClinPharm Prüfzentrum Frankfurt / aM
City
Frankfurt
ZIP/Postal Code
60596
Country
Germany
Facility Name
ClinPharm Prüfzentrum Görlitz
City
Görlitz
ZIP/Postal Code
02826
Country
Germany
Facility Name
Clinical Research Hamburg
City
Hamburg
ZIP/Postal Code
22143
Country
Germany
Facility Name
Orthopädie Zentrum Altona
City
Hamburg
ZIP/Postal Code
22767
Country
Germany
Facility Name
ClinPharm International, Prüfzentrum Leipzig
City
Leipzig
ZIP/Postal Code
04103
Country
Germany
Facility Name
ClinPharm Prüfzentrum Magdeburg
City
Magdeburg
ZIP/Postal Code
39104
Country
Germany
Facility Name
Servizio di Reumatologia, Ospedale Privato Accreditato Nigrisoli
City
Bologna
ZIP/Postal Code
40138
Country
Italy
Facility Name
Dipartimento di Biomedicina - SOD Reumatologia - Azienda Ospedaliera Universitaria Careggi
City
Firenze
ZIP/Postal Code
50139
Country
Italy
Facility Name
Dipartimento di Medicina Interna Azienda Ospedaliero Universitaria Pisana-Stabilimento di Santa Chiara Pisa
City
Pisa
ZIP/Postal Code
56126
Country
Italy
Facility Name
Istituto di Reumatologia, "Policlinico Le Scotte" Università degli Studi di Siena
City
Siena
ZIP/Postal Code
53100
Country
Italy
Facility Name
Servicio de Reumatologia, Hospital de Basurto
City
Bilbao
ZIP/Postal Code
48013
Country
Spain
Facility Name
Servicio de Reumatologia, Hospital Universitario La Paz
City
Madrid
ZIP/Postal Code
28046
Country
Spain
Facility Name
Servicio de Reumatologia, Corporacio Sanitaria Parc Tauli, Hospital de Sabadell
City
Sabadell
ZIP/Postal Code
08208
Country
Spain
Facility Name
Servicio de Reumatologia, Hospital Universitario Virgen Macarena
City
Sevilla
ZIP/Postal Code
41009
Country
Spain
12. IPD Sharing Statement
Learn more about this trial
A Locally Injected Bradykinin Antagonist for TReatment of OSteoarthritiS
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