A double-blind, randomised placebo-controlled Phase I/IIa study to investigate the safety, tolerability and efficacy on pain of intra-articular ESBA105 applied to patients with severely painful osteoarthritis of the knee

• Conditions: Osteoarthritis of the knee; MedDRA version: 9.1Level: LLTClassification code 10031165Term: Osteoarthritis knee

• Registration Number: EUCTR2008-001712-21-DE
• Lead Sponsor: Delenex Therapeutics AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-10-30
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 126

Inclusion Criteria

• Signed and dated Informed Consent.
• Male or female.
• >= 40 years of age.
• Body mass index < 30.
• Negative pregnancy test for females of child bearing potential (pre-menopausal, < 2 years post-menopausal, not surgically sterile).
Female patients of childbearing potential and their partners must to use 2 forms of contraception (including 1 barrier method), from screening until 2 months after the injection with ESBA105.
Primary forms of contraception include intrauterine devices, oral contraceptive agents that the patient has already been using for at least 90 days before screening, and injectable/implantable/insertable hormonal birth control products. Secondary forms of contraception include diaphragms, latex condoms, and cervical caps.
• 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• Paracetamol and NSAIDs (apart from acetyl salicylic acid = 100 mg/day) must be withdrawn at least 24 hours prior to Screening (Day -7 [-3 days]).
• Paracetamol, which is allowed to be re-initiated after completion of Screening assessments (Day -7 [-3 days]), must be withdrawn again as of Day -3.
• 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 (e.g., Rosa canina (lithocin), Perna canaliculus (Grünlippenmuschelextrakt”), Harpagophytum procumbens (Teufelskralle”)) must be stable for at least 3 months prior to Screening.
• Use of non-pharmacological treatment modalities (e.g., physical therapy, biomechanical devices, magnetic therapy, ointments, and heating pads) must be stable for at least 3 months prior to Screening.
• Negative QuantiFERON-TB Gold test.
• Ability to comply with the study requirements

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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 (e.g., hemochromatosis, severe chondrocalcinosis characterised by linear calcification of the hyaline cartilage, major knee trauma (e.g., rupture of cruciate ligaments, joint fractures)).
• Relevant complex, radial or vertical meniscal tears if documented by pre-existing MRI scans.
• Isolated OA of the patello-femoral joint.
• Pain in the hip as assessed upon internal and external rotation of the hip joint that would confound measurement of the knee pain.
• Co-morbidity that would confound measurement of knee pain (i.e., myopathy, spinal canal stenosis, radiculopathy) at Screening, if documented by pre-existing imaging.
• More significant pain from the back than the knee 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.
• Clinical signs or symptoms of active knee infection at Screening or Baseline.
• Planned knee replacement during the course of the study.
• Local or systemic contraindication for an i.a. injection at Screening or Baseline.
• Treatment within 3 months prior to the injection with anticoagulant therapy.
• Treatment within 3 months prior to Screening or concomitant treatment with neuroleptic agents, monoamine oxidase inhibitors, serotonin/norepinephrine re uptake inhibitor, tricyclic antidepressants, anticonvulsants, or anti-parkinsonian drugs, potent analgesic agents (i.e., opiates).
• Treatment within 3 months prior to Screening or concomitant treatment with systemic corticosteroids.
• Skin barrier breakdown (e.g., psoriasis) at the knee where the injection would take place at Screening or Baseline.
• Any known sensitivity to E. coli derived products.
• Any i.a. injection (corticosteroids, hyaluronic acid, etc.) within the 3 months prior to Screening.
• History of high risk exposure to Mycobacterium tuberculosis.
• Positive urine opiate test.
• History of, or known current problems with drug or alcohol abuse at Screening.
• History or suspicion of unreliability, poor cooperation or non-compliance with medical treatment at Screening.
• HIV, hepatitis B or C infection.
• Uncontrolled diabetes mellitus or cardiovascular disease (NYHA criteria III + IV), incl. 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 including leukopenia (total white blood cell count <2.0 x 109/L) or thrombocytopenia (<150,000 / mm3) within 1 month prior to or at Screening.
• Moderately to severely impaired hepatic function, or laboratory values reflecting inadequate hepatic function (> 3 x upper limit of normal in ALT and AST at Screening).
• Received any live vaccine within 3 months prior to Screening.
• Receiving

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified