Study of Safety, Tolerability, Preliminary Efficacy of Intra-articular LNA043 Injections in Patients With Articular Cartilage Lesions and Knee Osteoarthritis.
A Two-part, Randomized, Placebo-controlled, Patient and Investigator Blinded, Study Investigating the Safety, Tolerability and Preliminary Efficacy of Intra-articular LNA043 Injections in Regenerating the Articular Cartilage of the Knee in Patients With Articular Cartilage Lesions (Part A) and in Patients With Knee Osteoarthritis (Part B).
ClinicalTrials.gov Identifier: NCT03275064
Novartis Reference Number: CLNA043X2202
Last Update: Dec 11, 2020
All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation.
Study Description
The purpose of this two-part study is to assess the efficacy, safety and tolerability of multiple intra-articular (i.a.) injections of LNA043 in regenerating the articular surface in patients with cartilage lesions of the knee (Part A) and knee osteoarthritis (Part B).
Interventions
Eligibility Criteria
Inclusion criteria 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 BMI >30 but ≤ 33kg/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 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 OA in the target knee by standard American College of Rheumatology (ACR) criteria at study start (clinical AND radiographic criteria)
Patient has a K&L grade 2 or 3 OA of the knee with 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.
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.
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.
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.
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
Study Locations
Contacts
Have a question?
Call 1-888-669-6682 or email [email protected]