Study of safety, tolerability and preliminary efficacy of multiple intra-articular LNA043 injections in patients with articular cartilage lesions andknee osteoarthritis.
- Conditions
- Acute cartilage injuries and osteoarthritisMedDRA version: 20.0Level: PTClassification code 10031161Term: OsteoarthritisSystem Organ Class: 10028395 - Musculoskeletal and connective tissue disordersTherapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]
- Registration Number
- EUCTR2016-004052-30-CZ
- Lead Sponsor
- ovartis Pharma AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 135
Part A
- Patient is =18 and =55 years old at time of screening.
- Patient has a body mass index (BMI) <30 kg/m2 at screening. For patients with a BMI >30 but = 33 kg/m2, eligibility will be decided by consultation with the sponsor.
- Patient has a symptomatic, single, articular cartilage defect of one knee, grade II or IIIA according to the ICRS classification, localized to either the femoral condyles/femoral trochlea or to the patella, based on MRI or arthroscopy performed within 9 months before screening visit and confirmed by screening 3T MRI.
- Patient has an onset of pain and impairment of function between two (2) months and two (2) years before screening.
- Patient reports a KOOS (sports and recreational activities subscale) score of 60 or less at both screening and Day 1.
Inclusion Criteria Part B
- Patient is =18 and =75 years old at time of screening.
- Patient has a body mass index (BMI) =35 kg/m2 at screening
- Diagnosis of femorotibial osteoarthritis(OA) in the target knee by standard American
College of Rheumatology (ACR) criteria at study start (clinical AND
radiographic criteria)
- Patient has a Kellgren & Lawrence (K&L) grade 2 or 3 OA of the knee with Joint Space Width (JSW) 2-4 mm
evaluated with X-Ray at screening.
- Patient must have symptomatic disease predominantly in one (the
index) knee, with minimal or no symptoms in the contralateral knee.
Symptomatic disease is defined as having pain in the knee more
than 50% of the days during the last 3 months from screening.
Other protocol defined inclusion criteria may apply.
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 115
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20
Exclusion criteria Part A & B
- Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 15 days after stopping of investigational drug.
- Patient has had surgical treatment of the target knee using
mosaicplasty, microfracture, meniscectomy >50% (Note: prior
diagnostic arthroscopy with debridement and lavage, <50%
meniscectomy, lateral release, patellar realignment, medial
patellofemoral ligament reconstruction are acceptable if performed at least 2 months prior to screening; anteriorcruciate ligament
reconstrucion is acceptable if performed 12 months prior to screening, or less if restoration of joint function is evident, and agreed by the sponsor).
- Patient has an unstable target knee joint or insufficiently reconstructed ligaments based on medical history and physical examination by the investigator.
Prohibited medication updated with reference to dosing (formerly
screening).
Exclusion Criteria Part A only
- Regular smokers (> 5 cigarettes/day). Urine cotinine levels will be
measured during screening for all patients. Regular smokers will be
defined as any patient who reports tobacco use of > 5 cigarettes/day
and/or who has a urine cotinine = 500 ng/mL.
- Patient has radiologically apparent degenerative joint disease in the target knee as determined by Kellgren and Lawrence grade =2 based on X-ray evaluation performed within 9 months from screening.
- Patient has patellofemoral dysplasia Dejour Grade B-D based on X-ray evaluation performed within 9 months from screening.
- Patient has malalignment (valgus- or varus-deformity) in the target
knee = 5° based on X-ray evaluation performed within 9 months from screening. In suspected cases, the mechanical axis must be established radiographically through complete leg imaging during standing and in postero-anterior (PA) projection.
Exclusion Criteria Part B only
- Regular smokers (> 10 cigarettes/day).
- Clinical signs of inflammation (i.e., redness) in the target knee.
- History of knee replacement (unilateral or total) in either knee.
- Presence of severe hip OA conditioning lower limb function according to PI's evaluation.
- Nephrotic syndrome and/or significant proteinuria
- History of coagulopathy or medical condition requiring anticoagulation which would preclude knee injection
- Patient has malalignment (valgus- or varus-deformity) in the target
knee = 7.5° based on X-ray evaluation. In suspected cases, the
mechanical axis must be established radiographically through complete leg imaging during standing and in postero-anterior (PA)
projection.
Other protocol defined exclusion criteria's may apply
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: • To assess the efficacy of multiple i.a. injections of LNA043 in regenerating the articular cartilage tissue<br>• To assess safety and local tolerability of multiple i.a. injections of LNA043;Secondary Objective: • To assess the extent of the repair cartilage tissue following multiple i.a. injections of LNA043<br>• To evaluate systemic and local PK of LNA043 following multiple i.a. injections of LNA043<br>• To assess the potential immunogenicity of LNA043;Primary end point(s): • Articular cartilage bilayer collagen organization evaluated with MRI<br>and measured in milliseconds up to Week 28 (Part A)<br>• Number of patients with any adverse events, serious adverse events and death up to end of study<br>• Change in cartilage volume/thickness in the index region up to Week 52 (Part B);Timepoint(s) of evaluation of this end point: as defined under E.5.1
- Secondary Outcome Measures
Name Time Method Secondary end point(s): • Change in volume of cartilage defect filling evaluated with MRI at<br>Week 16 and 28 (Part A)<br>• Maximum Observed Plasma Concentration (Cmax) measured in ng/mL at 0 (pre-dose), 15 min, 60 min and 120 min post-dose Week 1, Week 2, Week 3, Week 4 (Part A and Part B)<br>• Potential immunogenicity of LNA043 presence and characterisation of anti-LNA043 antibodies in serum at Week 1, Week 3, Week 6, Week 16,<br>Week 28 (Part A and Part B)<br>• Area Under the Plasma Concentration-time Curve From 0 to the Last Measurable Concentration (AUClast) at 0 (pre-dose), 15 min, 60 min and 120 min post-dose Week 1, Week 2, Week 3, Week 4 (Part A and Part B)<br>• Articular cartilage bi-layer collagen organization<br>evaluated with T2 relaxation times in milliseconds at Week 28 and Week 52 (Part B);Timepoint(s) of evaluation of this end point: as defined under E.5.2