- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00819572
Study of Intra-articular DLX105 Applied to Patients With Severely Painful Osteoarthritis of the Knee
September 23, 2010 updated by: ESBATech AG
A Double-blind, Randomised, Placebo-controlled Phase I/IIa Study to Investigate the Safety, Tolerability and Efficacy on Pain of Intra-articular DLX105 Applied to Patients With Severely Painful Osteoarthritis of the Knee
The purpose of this study is to determine whether an intra-articular injection of DLX105 to the knee joint of patients suffering from severly painful osteoarthritis is safe and reduces pain.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
Treatment options for patients suffering from osteoarthritis remain limited.
TNF-alpha has been identified as a major pro-inflammatory component inducing and perpetuating peripheral hyperalgesia and cartilage degeneration in various preclinical studies.
DLX105 is an antibody fragment of comparably low molecular weight, associated with an exceptional local biodistribution pattern upon intra-articular injection.
In addition, due to its short systemic half life as compared to conventional monoclonal antibodies, systemic exposure to DLX105 upon intra-articular administration is low.
This study is designed to determine the safety and local tolerability profile of single intra-articular injections of ESBA105 as well as to define DLX105's effect size and effect duration in reducing pain of patients suffering from severely painful osteoarthritis of the knee.
The study will be conducted in two sequential parts.
In a first part, 4 different doses of DLX105 will be compared in a sequential, escalating scheme against placebo treatment in a total of 24 patients.
In the second part of the study, two doses of DLX105 chosen based on safety data from the first part will be compared to placebo treatment in a total of 102 patients.
Study Type
Interventional
Enrollment (Actual)
27
Phase
- Phase 2
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
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Erlangen, Germany, 91054
- Prof. Dr. med. Georg Schett
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Hamburg, Germany, 22143
- Dr. René Martz
-
Hannover, Germany, 30625
- Dr. Sven Ostermeier
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Munich, Germany, 80809
- Prof. Dr. Manfred Hartard
-
-
-
-
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Aarau, Switzerland, 5000
- Rheumaklinik Kantonsspital Aarau
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Basel, Switzerland, 4055
- Rheumatologische Universitäts-Poliklinik, Felix-Platter Spital Basel
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Lausanne, Switzerland, 1005
- Service de rhumatologie, Centre Hospitalier Universitaire, Lausanne
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St.Gallen, Switzerland, 9007
- Kantonsspital St.Gallen, Rheumatologie
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Zurich, Switzerland, 8038
- Zentrum für Rheuma und Knochenerkrankungen
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Zürich, Switzerland, 8091
- Universitätsspital Zürich, Rheumaklinik
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
40 years and older (ADULT, OLDER_ADULT)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Body mass index < 30.
- Patients with diagnosed OA of the knee (unilateral or bilateral) according to the American College of Rheumatology (ACR) Criteria for classification of idiopathic OA (clinical and radiological criteria) of the knee at Screening (for ACR criteria, see Appendix 16.1).
- Radiographic evidence of tibiofemoral OA within the last 6 months before Screening, consisting of Grade II or Grade III changes, according to Kellgren-Lawrence grading system.
- Presence of pain in the index knee (in case of bilateral OA, "index knee" is the more painful knee) defined by a level of ≥ 60 mm on a 100 mm (linear) VAS at Screening.
- Paracetamol and NSAIDs (apart from acetyl salicylic acid ≤ 100 mg/day) must be withdrawn at least 24 hours prior to Screening .
- Doses of "chondroprotective" agents containing glucosamine and/or chondroitin sulphate must be stable for at least 3 months prior to Screening.
- Doses of any non-prescription medication claiming effects on signs or symptoms of OA must be stable for at least 3 months prior to Screening.
- Use of non-pharmacological treatment modalities must be stable for at least 3 months prior to Screening.
- Negative QuantiFERON-TB Gold test.
Exclusion Criteria:
- Radiographic evidence of tibiofemoral OA within the last 6 months before Screening, consisting of Grade IV, according to Kellgren-Lawrence grading system.
- Instability of the index knee joint of > 10° as assessed by goniometer at Screening.
- Arthroscopic or open surgery to the index knee joint within 6 months prior to Screening.
- Post-traumatic or any other secondary OA of the knee.
- Isolated OA of the patello-femoral joint.
- Co-morbidity that would confound measurement of knee pain
- Evidence of any inflammatory arthritis.
- History of Reiter's Syndrome, RA, psoriatic arthritis, ankylosing spondylitis, lymphoma, arthritis associated with inflammatory bowel disease, sarcoidosis, amyloidosis, or any other inflammatory disease (immune mediated inflammatory disease) that may affect the knee.
- Local or systemic contraindication for an i.a. injection at Screening or Baseline.
- Any i.a. injection (corticosteroids, hyaluronic acid, etc.) within the 3 months prior to Screening.
- History of high risk exposure to Mycobacterium tuberculosis.
- Human immunodeficiency virus (HIV), hepatitis B or hepatitis C infection.
- Uncontrolled diabetes or cardiovascular disease (New York Heart Association criteria III + IV), including uncontrolled hypertension (> 160/100 mmHg).
- Active infectious episodes, or history of recurrent or chronic systemic infections.
- Malignancy within 5 years prior to Screening, except for surgically-cured non melanoma skin cancer or cervical carcinoma in situ.
- Significant haematological disease within 1 month prior to Screening.
- Moderately to severely impaired hepatic function, or laboratory values reflecting inadequate hepatic function
Additional criteria for the sub-population of patients undergoing MRI:
- Contraindications to MRI.
- Known allergy to gadolinium contrast material.
- Presence of chronic renal failure defined by a calculated creatinine clearance (CrCl) of < 60 mL/min, using the Cockcroft-Gault estimate for GFR
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: QUADRUPLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
PLACEBO_COMPARATOR: 3
|
|
EXPERIMENTAL: 1
DLX105 low dose
|
Comparison of two different doses of intra-articular DLX105
|
EXPERIMENTAL: 2
DLX105 high dose
|
Comparison of two different doses of intra-articular DLX105
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Change from Baseline (Day 0) to Day 7 in a 100mm Visual Analogue Scale (VAS) to assess the intensity of knee pain.
Time Frame: Day 7 after intra-articular injection
|
Day 7 after intra-articular injection
|
Safety assessment during the study period. Safety endpoints will include the nature and incidence of AEs, physical examination findings, changes in vital signs, and laboratory test results.
Time Frame: 8 weeks / 12 weeks
|
8 weeks / 12 weeks
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Change from baseline in Western Ontario and McMaster Universities Osteoarthritis (WOMAC™) scoring
Time Frame: Day 7 after intra-articular injection
|
Day 7 after intra-articular injection
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Study Chair: Prof. Georg Schett, MD, University Hospital of Erlangen, Germany
- Principal Investigator: Prof. Hansjörg Häuselmann, MD, Rheumazentrum, Zurich Switzerland (Country Coordinator)
- Principal Investigator: PD.Dr. Diego Kyburz, MD, University Hospital Zurich, Switzerland (Country Coordinator)
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
December 1, 2008
Primary Completion (ACTUAL)
September 1, 2010
Study Completion (ACTUAL)
September 1, 2010
Study Registration Dates
First Submitted
January 8, 2009
First Submitted That Met QC Criteria
January 8, 2009
First Posted (ESTIMATE)
January 9, 2009
Study Record Updates
Last Update Posted (ESTIMATE)
September 24, 2010
Last Update Submitted That Met QC Criteria
September 23, 2010
Last Verified
September 1, 2010
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- DLX105CRD02
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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