Study of safety, tolerability and preliminary efficacy of multiple intra-articular LNA043 injections in patients with articular cartilage lesions.
- Conditions
- Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]Acute cartilage injuriesMedDRA version: 20.0Level: PTClassification code 10031161Term: OsteoarthritisSystem Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
- Registration Number
- EUCTR2016-004052-30-SE
- Lead Sponsor
- ovartis Pharma AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 60
- 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.
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 60
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
-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.
- Regular smokers (consummation of >5 cigarettes/day in the previous
3 months). 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 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; anterior cruciate 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 (including but not limited to
posttraumatic or congenital laxity) or insufficiently reconstructed
ligaments based on medical history and physical examination by the
investigator.
- Patient has patellofemoral dysplasia Dejour Grade B-D based on X-ray
or MRI evaluation.
- Patient has malalignment (valgus- or varusdeformity) in the target
knee = 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 organisation evaluated with T2<br>relaxation times measured in superficial and deep layers<br>by T2 mapping MRI at Week 16 and 28<br>• Number of patients with any adverse events, serious adverse events and death up to end of study;Timepoint(s) of evaluation of this end point: as defined under E.5.1
- Secondary Outcome Measures
Name Time Method Secondary end point(s): • Percentage (%) of cartilage defect filling evaluated with MRI at Week 16 and 28<br>• Maximum Observed Plasma Concentration (Cmax) at 0 (pre-dose), 15 min, 60 min and 120 min post-dose Week 1, Week 2, Week 3, Week 4<br>• Potential immunogenicity of LNA043 presence and characterisation of anti-LNA043 antibodies in serum at Week 1, Week 3, Week 6, Week 16, Week 28<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;Timepoint(s) of evaluation of this end point: as defined under E.5.2