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    Summary
    EudraCT Number:2016-004052-30
    Sponsor's Protocol Code Number:CLNA043X2202
    National Competent Authority:Czechia - SUKL
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2017-03-16
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedCzechia - SUKL
    A.2EudraCT number2016-004052-30
    A.3Full title of the trial
    A two part randomized, placebo-controlled, patient and investigator blinded, Proof of Concept study investigating the safety, tolerability and preliminary efficacy of multiple 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).
    Randomizované, placebem kontrolované, zaslepené pro subjekty a zkoušející, ověřovací (proof of concept) klinické hodnocení bezpečnosti, snášenlivosti a předběžné účinnosti opakovaného intraartikulárního podání injekcí přípravku LNA043 na regeneraci kloubní chrupavky kolene, skládající se ze dvou částí – u pacientů s poškozením kloubní chrupavky (část A) a u pacientů s OA kolene (část B)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Study of safety, tolerability and preliminary efficacy of multiple intra-articular LNA043 injections in patients with articular cartilage lesions and
    knee osteoarthritis.
    A.4.1Sponsor's protocol code numberCLNA043X2202
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT03275064
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorNovartis Pharma AG
    B.1.3.4CountrySwitzerland
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportNovartis Pharma AG
    B.4.2CountrySwitzerland
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationNovartis s.r.o.
    B.5.2Functional name of contact pointInformační služba – klin. hodnocení
    B.5.3 Address:
    B.5.3.1Street AddressNa Pankráci 1724/129
    B.5.3.2Town/ cityPraha 4
    B.5.3.3Post code140 00
    B.5.3.4CountryCzechia
    B.5.4Telephone number+420 2 25775 111
    B.5.5Fax number+420 2 25775 205
    B.5.6E-maildotazy.klinickehodnoceni@novartis.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.2Product code LNA043
    D.3.4Pharmaceutical form Powder for solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntraarticular use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNTBD
    D.3.9.2Current sponsor codeLNA043
    D.3.9.4EV Substance CodeSUB179108
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboPowder for solution for injection
    D.8.4Route of administration of the placeboIntraarticular use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Acute cartilage injuries and osteoarthritis
    E.1.1.1Medical condition in easily understood language
    Acute cartilage injuries and osteoarthritis
    E.1.1.2Therapeutic area Diseases [C] - Musculoskeletal Diseases [C05]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10031161
    E.1.2Term Osteoarthritis
    E.1.2System Organ Class 10028395 - Musculoskeletal and connective tissue disorders
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    • To assess the efficacy of multiple i.a. injections of LNA043 in regenerating the articular cartilage tissue
    • To assess safety and local tolerability of multiple i.a. injections of LNA043
    E.2.2Secondary objectives of the trial
    • To assess the extent of the repair cartilage tissue following multiple i.a. injections of LNA043
    • To evaluate systemic and local PK of LNA043 following multiple i.a. injections of LNA043
    • To assess the potential immunogenicity of LNA043
    E.2.3Trial contains a sub-study No
    E.3Principal 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 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.
    E.4Principal exclusion criteria
    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
    E.5 End points
    E.5.1Primary end point(s)
    • Articular cartilage bilayer collagen organization evaluated with MRI
    and measured in milliseconds up to Week 28 (Part A)
    • Number of patients with any adverse events, serious adverse events and death up to end of study
    • Change in cartilage volume/thickness in the index region up to Week 52 (Part B)
    E.5.1.1Timepoint(s) of evaluation of this end point
    as defined under E.5.1
    E.5.2Secondary end point(s)
    • Change in volume of cartilage defect filling evaluated with MRI at
    Week 16 and 28 (Part A)
    • 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)
    • Potential immunogenicity of LNA043 presence and characterisation of anti-LNA043 antibodies in serum at Week 1, Week 3, Week 6, Week 16,
    Week 28 (Part A and Part B)
    • 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)
    • Articular cartilage bi-layer collagen organization
    evaluated with T2 relaxation times in milliseconds at Week 28 and Week 52 (Part B)
    E.5.2.1Timepoint(s) of evaluation of this end point
    as defined under E.5.2
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial5
    E.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned6
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA8
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    United States
    Czechia
    Denmark
    E.8.7Trial has a data monitoring committee No
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years4
    E.8.9.1In the Member State concerned months10
    E.8.9.1In the Member State concerned days14
    E.8.9.2In all countries concerned by the trial years4
    E.8.9.2In all countries concerned by the trial months10
    E.8.9.2In all countries concerned by the trial days14
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 115
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 20
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state12
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 78
    F.4.2.2In the whole clinical trial 135
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    After study participation, the patients will continue to be treated according to the local standard clinical practice
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2017-06-23
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2017-04-12
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2022-09-06
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