Study of Intra-articular DLX105 Applied to Patients With Severely Painful Osteoarthritis of the Knee

This study has been completed.
Sponsor:
Information provided by:
ESBATech AG
ClinicalTrials.gov Identifier:
NCT00819572
First received: January 8, 2009
Last updated: September 23, 2010
Last verified: September 2010
  Purpose

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.


Condition Intervention Phase
Osteoarthritis
Biological: DLX105, a single-chain (scFv) antibody fragment against TNF-alpha
Drug: Placebo
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by ESBATech AG:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Change from baseline in Western Ontario and McMaster Universities Osteoarthritis (WOMAC™) scoring [ Time Frame: Day 7 after intra-articular injection ] [ Designated as safety issue: No ]

Enrollment: 27
Study Start Date: December 2008
Study Completion Date: September 2010
Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
DLX105 low dose
Biological: DLX105, a single-chain (scFv) antibody fragment against TNF-alpha
Comparison of two different doses of intra-articular DLX105
Experimental: 2
DLX105 high dose
Biological: DLX105, a single-chain (scFv) antibody fragment against TNF-alpha
Comparison of two different doses of intra-articular DLX105
Placebo Comparator: 3 Drug: Placebo

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.

  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00819572

Locations
Germany
Prof. Dr. med. Georg Schett
Erlangen, Germany, 91054
Dr. René Martz
Hamburg, Germany, 22143
Dr. Sven Ostermeier
Hannover, Germany, 30625
Prof. Dr. Manfred Hartard
Munich, Germany, 80809
Switzerland
Rheumaklinik Kantonsspital Aarau
Aarau, Switzerland, 5000
Rheumatologische Universitäts-Poliklinik, Felix-Platter Spital Basel
Basel, Switzerland, 4055
Service de rhumatologie, Centre Hospitalier Universitaire, Lausanne
Lausanne, Switzerland, 1005
Kantonsspital St.Gallen, Rheumatologie
St.Gallen, Switzerland, 9007
Zentrum für Rheuma und Knochenerkrankungen
Zurich, Switzerland, 8038
Universitätsspital Zürich, Rheumaklinik
Zürich, Switzerland, 8091
Sponsors and Collaborators
ESBATech AG
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)
  More Information

No publications provided

Responsible Party: Hamish Cameron, CEO, Delenex AG
ClinicalTrials.gov Identifier: NCT00819572     History of Changes
Other Study ID Numbers: DLX105CRD02
Study First Received: January 8, 2009
Last Updated: September 23, 2010
Health Authority: Switzerland: Swissmedic and Ethics Committee
Germany: PEI (Paul-Ehrlich-Institut) and Ethics Committee

Keywords provided by ESBATech AG:
Osteoarthritis
TNF-alpha
DLX105
scFv antibody fragment
pain
fragment
antibody fragment

Additional relevant MeSH terms:
Osteoarthritis
Osteoarthritis, Knee
Arthritis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Antibodies
Immunoglobulins
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 30, 2014