Osteoarthritis, KneePhase 2ALBATROSSNCT01091116
A Locally Injected Bradykinin Antagonist for TReatment of OSteoarthritiS
A Phase 2 study testing MEN16132 - 0.125 mg, MEN16132 - 0.25 mg and MEN16132 - 0.5 mg in people with Osteoarthritis, Knee, run by Menarini Group at 23 sites in 4 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- Osteoarthritis, Knee
- What is being tested?
- MEN16132 - 0.125 mg, MEN16132 - 0.25 mg and MEN16132 - 0.5 mg
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 423 participants
- Where
- 23 sitesin 4 countries
- Study dates
- Mar 2010to Mar 2011
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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 locations and contacts
23 sites in 4 countries.
23 sites in 4 countries
Germany12 sites
Rheumatologie/Immunologie - Rheumazentrum, Krankenhaus Doberan
Bad Doberan, 18209
Klinik für Rheumatologie und Klinische Immunologie, Charité - Campus Charité Mitte
Berlin, 10117
Orthopädische Praxis Dr. Wagenitz
Berlin, 12247
ClinPharm International, Prüfzentrum Bochum
Bochum, 44787
ClinPharm International, Prüfzentrum Dresden
Dresden, 01067
Medizinische Klinik 3, Universität Erlangen-Nürnberg
Erlangen, 91054
ClinPharm Prüfzentrum Frankfurt / aM
Frankfurt, 60596
ClinPharm Prüfzentrum Görlitz
Görlitz, 02826
Clinical Research Hamburg
Hamburg, 22143
Orthopädie Zentrum Altona
Hamburg, 22767
ClinPharm International, Prüfzentrum Leipzig
Leipzig, 04103
ClinPharm Prüfzentrum Magdeburg
Magdeburg, 39104
Italy4 sites
Servizio di Reumatologia, Ospedale Privato Accreditato Nigrisoli
Bologna, 40138
Dipartimento di Biomedicina - SOD Reumatologia - Azienda Ospedaliera Universitaria Careggi
Florence, 50139
Dipartimento di Medicina Interna Azienda Ospedaliero Universitaria Pisana-Stabilimento di Santa Chiara Pisa
Pisa, 56126
Istituto di Reumatologia, "Policlinico Le Scotte" Università degli Studi di Siena
Siena, 53100
Spain4 sites
Servicio de Reumatologia, Hospital de Basurto
Bilbao, 48013
Servicio de Reumatologia, Hospital Universitario La Paz
Madrid, 28046
Servicio de Reumatologia, Corporacio Sanitaria Parc Tauli, Hospital de Sabadell
Sabadell, 08208
Servicio de Reumatologia, Hospital Universitario Virgen Macarena
Seville, 41009
France3 sites
Centre Hospitalier Régional - Hôpital Porte Madeleine
Orléans, 45000
Hôtel Dieu - GHU Ouest
Paris, 75181
Department of Rheumatology, Purpan University Hospital
Toulouse, 31300
About this study
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
The purpose of this study is to determine whether intra-articular (knee joint) administration of MEN16132 is effective reducing the pain from knee osteoarthritis.
Read the 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.
- Conditions
- Osteoarthritis, Knee
- Being tested
- MEN16132 - 0.125 mg, MEN16132 - 0.25 mg, MEN16132 - 0.5 mg, Placebo
- Keywords
- Injections, Intra-Articular
- Medical subject headings
- Osteoarthritis, Knee
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MEN16132 - 0.125 mgDrug
Also called fasitibant 0.125 mg
Intra-articular administration of two low doses of MEN16132 at 2-week interval.
MEN16132 - 0.25 mgDrug
Also called fasitibant 0.25 mg
Intra-articular injection of two intermediate doses of MEN16132 at 2-week interval
MEN16132 - 0.5 mgDrug
Also called fasitibant 0.5 mg
Intra-articular injection of two high doses of MEN16132 at 2-week interval
MEN16132 - 0.5 mgDrug
Also called fasitibant 0.5 mg
Single intra-articular injection of one high dose of MEN16132, followed by one dose of placebo at 2-week interval
PlaceboDrug
Intra-articular injection of 2 doses of Placebo control at 2-week interval
| Study group | Role | What they receive |
|---|---|---|
| Double dose MEN16132 0.125 mg | Experimental | Intra-articular administration of two 0.125 mg doses of MEN16132 at 2-week interval. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: MEN16132 - 0.5 mg |
| Placebo | Placebo comparator | Intra-articular administration of two doses of Placebo at 2-week interval. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: over the 3 weeks after the first administration
Secondary outcomes (8)
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.
Measured: up to 3 months after first dose
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.
Measured: up to 3 months after first dose
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.
Measured: up to 3 months after first dose
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.
Measured: up to 3 months after first dose
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.
Measured: over the 3 weeks after the first administration
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.
Measured: over the 3 weeks after the first administration
Adverse Event Reports
Incidence of spontaneously reported adverse events
Measured: up to 4 months after screening
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.
Measured: up to 4 months from screening
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Mar 2010 (estimated)
- Study startMar 2010
- Primary completionFeb 2011
- Study completionMar 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Osteoarthritis, KneeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 423 participants (actual)
Sponsor and investigators
- Lead sponsor
- Menarini Group
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Karel Pavelka, Prof MD, Principal investigator, Institute of Rheumatology, Charles University Prague
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01091116
- Sponsor's protocol ID
- BKOS-02
- Other IDs
- 2009-014918-99, 2009
- Acronym
- ALBATROSS
- Status last verified
- Jan 2013
- First submitted
- 18 Mar 2010
- Last updated
- 18 Feb 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Feb 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01091116
- Acronym / sponsor ID
- ALBATROSS / BKOS-02
- Conditions
- Osteoarthritis, Knee
- Keywords
- Injections, Intra-Articular
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 423 participants (actual)
- Lead sponsor
- Menarini GroupIndustry (pharma, biotech, devices)
- Study start
- Mar 2010
- Primary completion
- Feb 2011 (actual)
- Study completion
- Mar 2011 (actual)
- First posted
- 23 Mar 2010 (estimated)
- Results
- Posted 18 Feb 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Double dose MEN16132 0.125 mg | Experimental | Drug: MEN16132 - 0.125 mgIntra-articular administration of two 0.125 mg doses of MEN16132 at 2-week interval. |
| Double dose MEN16132 0.25 mg | Experimental | Drug: MEN16132 - 0.25 mgIntra-articular administration of two 0.25 mg doses of MEN16132 at 2-week interval. |
| Double dose MEN16132 0.5 mg | Experimental | Drug: MEN16132 - 0.5 mgIntra-articular administration of two 0.5 mg doses of MEN16132 at 2-week interval. |
| Single dose MEN16132 0.5 mg | Experimental | Drug: MEN16132 - 0.5 mgIntra-articular administration of one 0.5 mg dose of MEN16132 followed by one intra-articular injection of placebo at 2-week interval. |
| Placebo | Placebo comparator | Drug: PlaceboIntra-articular administration of two doses of Placebo at 2-week interval. |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MEN16132 - 0.125 mgAlso: fasitibant 0.125 mgIntra-articular administration of two low doses of MEN16132 at 2-week interval. | Drug | Double dose MEN16132 0.125 mg |
| MEN16132 - 0.25 mgAlso: fasitibant 0.25 mgIntra-articular injection of two intermediate doses of MEN16132 at 2-week interval | Drug | Double dose MEN16132 0.25 mg |
| MEN16132 - 0.5 mgAlso: fasitibant 0.5 mgIntra-articular injection of two high doses of MEN16132 at 2-week interval | Drug | Double dose MEN16132 0.5 mg |
| MEN16132 - 0.5 mgAlso: fasitibant 0.5 mgSingle intra-articular injection of one high dose of MEN16132, followed by one dose of placebo at 2-week interval | Drug | Single dose MEN16132 0.5 mg |
| PlaceboIntra-articular injection of 2 doses of Placebo control at 2-week interval | Drug | Placebo |
Primary outcome
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.
8 secondary outcomes
WOMAC VA 3.1.B Score (Knee Stiffness)
Time frame: up to 3 months after first dose
WOMAC VA 3.1. C Score (Function)
Time frame: up to 3 months after first dose
Percentage of Treatment Responders According to OMERACT-OARSI Responder Criteria
Time frame: up to 3 months after first dose
Patient Global Assessment
Time frame: up to 3 months after first dose
WOMAC VA 3.1A - Total Pain Score by Body Mass Index [BMI <= 25]
Time frame: over the 3 weeks after the first administration
WOMAC VA 3.1A - Total Pain Score by Body Mass Index -[BMI > 25]
Time frame: over the 3 weeks after the first administration
Adverse Event Reports
Time frame: up to 4 months after screening
Clinically Significant Abnormal Laboratory Tests
Time frame: up to 4 months from screening
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Feb 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Karel Pavelka, Prof MD principal investigator
Institute of Rheumatology, Charles University Prague
23 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing MEN16132 - 0.125 mg, MEN16132 - 0.25 mg and MEN16132 - 0.5 mg in people with Osteoarthritis, Knee, run by Menarini Group at 23 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Feb 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 23 sites in Germany, Italy, Spain, France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Feb 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
WOMAC VA 3.1 A Score (Total Pain) (time frame: over the 3 weeks after the first administration). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Feb 2013.