Study to investigate the safety and efficacy of anti-inflammatory (Canakinumab) and cartilage-stimulating medications (LNA043) injected into the knee joint, in participants with knee osteoarthritis (OA)
Descrizione riassuntiva dello studio
This is a Phase 2a study to demonstrate the concept with four treatment arms (TA1-4) to evaluate the effect of LNA043 in patients with symptomatic knee OA with inflammation, confirmed radiologically by MRI. In this study, participants will be randomly assigned to the 4 treatment arms. Participants may receive placebo and LNA043, placebo, Canakinumab and LNA043, or Canakinumab as the study medication. Patients will receive up to four injections into the knee joint within a 10-week treatment period and will be followed up to one year after the first dose. In Switzerland, the participation of 7 patients with symptomatic knee OA with inflammation is planned. A total of 138 patients will participate in the study. The aim of the current study is to assess whether the cartilage-preserving or regenerating effect of the LNA043 injection in patients with inflammatory knee OA can be demonstrated, to examine whether a potential negative impact of inflammation on the potential positive effect of LNA043 on cartilage regeneration can be overcome by a combination treatment with an anti-inflammatory therapy (Canakinumab injection), and to evaluate the efficacy of Canakinumab injections for pain relief and other clinical symptoms as well as to improve function. This study has two main objectives: to evaluate the efficacy of LNA043 injections compared to no LNA043 injection in terms of preservation or regeneration of joint cartilage tissue by measuring the change in cartilage volume at week 28 compared to baseline, and to evaluate the efficacy of a single injection of Canakinumab compared to placebo for the relief of OA pain by measuring the change from baseline in the KOOS pain subscale (Knee injury and Osteoarthritis Outcome Score) at week 12.
(BASEC)
Intervento studiato
Participants will be assigned in a ratio of 1:2:1:2 to one of the following 4 treatment arms (TA): TA1: Single injection of placebo to Canakinumab into the knee, followed by three injections of 40 mg LNA043 every four weeks; TA2: Single injection into the knee of placebo to Canakinumab; TA3: Single injection of 600 mg Canakinumab into the knee, followed by three injections of 40 mg LNA043 every four weeks; TA4: Single injection of 600 mg Canakinumab into the knee. Safety assessments include physical examinations, ECGs, vital signs, clinical laboratory tests, tissue samples, pregnancy and fertility assessments, as well as monitoring for adverse events and serious adverse events. For pain assessment, a pain diary and some questionnaires must be completed regularly.
(BASEC)
Malattie studiate
Knee osteoarthritis (OA) with inflammation
(BASEC)
• Male or female patients aged 40 to 80 years inclusive, with a diagnosis of primary tibiofemoral knee OA according to the clinical and radiological standard criteria of the American College of Rheumatology (ACR); • Moderate to severe OA pain in the target knee and active synovial inflammation, defined as moderate or severe according to contrast-enhanced MRI; • Radiological disease KL grade 2 to 4 knee OA and joint space width (JSW) 2.0-4.0 mm (males) or 1.5-3.5 mm (females) in the medial tibiofemoral compartment of the target knee, confirmed by X-rays at screening 1. (BASEC)
Criteri di esclusione
• Previous or planned surgical procedures; • Knee replacement (partial or total) in both knees; • Arthroscopy or lavage in either knee, within 6 months prior to screening 1 or planned during the study; • Any other previous surgical intervention on the target knee or planned within 12 months prior to screening 1 or during the study for the contralateral knee, including mosaicplasty, microfracture, meniscectomy >50% or osteotomy; • Occurrence of symptoms or diagnosis of primary osteoarthritis in other joints than the knees less than 3 months prior to screening 1; moderate to severe pain in the contralateral knee on most days in the last 3 months prior to screening 1, as assessed by the patient. (BASEC)
Luogo dello studio
Losanna, San Gallo
(BASEC)
Sponsor
Novartis Pharma AG
(BASEC)
Contatto per ulteriori informazioni sullo studio
Persona di contatto in Svizzera
Juliane Kuehn
+41 792951680
juliane.kuehn@clutternovartis.comNovartis Pharma AG
(BASEC)
Informazioni generali
SIA Novartis Baltics Estonian Branch
+372 663 0810
juliane.kuehn@clutternovartis.com(ICTRP)
Informazioni scientifiche
SIA Novartis Baltics Estonian Branch
+372 663 0810
juliane.kuehn@clutternovartis.com(ICTRP)
Nome del comitato etico approvante (per studi multicentrici solo il comitato principale)
Ethikkommission Ostschweiz EKOS
(BASEC)
Data di approvazione del comitato etico
06.10.2022
(BASEC)
ID di studio ICTRP
EUCTR2020-003631-21 (ICTRP)
Titolo ufficiale (approvato dal comitato etico)
A randomized, four-arm, canakinumab placebo-controlled, participant, investigator and sponsor-blinded study investigating the safety, tolerability and efficacy of intra-articular canakinumab followed by intra-articular LNA043 in patients with knee osteoarthritis (BASEC)
Titolo accademico
A randomized, four-arm, canakinumab placebo-controlled, participant, investigator and sponsor-blinded study investigating the safety, tolerability and efficacy of intra-articular canakinumab followed by intra-articular LNA043 in patients with knee osteoarthritis (ICTRP)
Titolo pubblico
A safety and efficacy study of anti-inflammatory (canakinumab) and cartilage stimulating (LNA043) drugs injected into the knee joint of participants with knee osteoarthritis (OA) (ICTRP)
Malattie studiate
osteoarthritis
MedDRA version: 21.1Level: LLTClassification code 10023476Term: Knee osteoarthritisSystem Organ Class: 100000004859;Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05] (ICTRP)
Intervento studiato
Product Code: LNA043
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: Not available
Current Sponsor code: LNA043
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-
Trade Name: Ilaris
Product Name: canakinumab
Product Code: ACZ885
Pharmaceutical Form: Solution for injection
INN or Proposed INN: CANAKINUMAB
CAS Number: 914613-48-2
Current Sponsor code: ACZ885
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 150-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Intraarticular use
(ICTRP)
Tipo di studio
Interventional clinical trial of medicinal product (ICTRP)
Disegno dello studio
Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 4 (ICTRP)
Criteri di inclusione/esclusione
Gender:
Female: yes
Male: yes
Inclusion criteria:
- Moderate to severe OA pain (corresponding to NRS Pain =5 to =9) in the target knee for the majority of days in the last 3 months prior to Screening
- KOOS pain subscale <60 for the target knee during Screening
- High sensitivity C-reactive Protein (hsCRP) =1.8 mg/L
- Radiographic KL grade 2 to 4 knee OA and joint space width (JSW) 2.0-4.0 mm (men) or 1.5-3.5 mm (women) in the medial tibiofemoral compartment (TFC) in the target knee
- Contrast-enhanced MRI (CE-MRI) diagnosed moderate or severe knee synovitis based on an established synovititis scoring system (moderate score 9-12 or severe score =13)
- 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 40
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 98
(ICTRP)
Exclusion criteria:
- History of, or planned; knee replacement(partial or total) in either knee; arthroscopy or lavage in either knee within 6 months prior to screening; any other previous surgical intervention in the target knee, or for the contralateral knee within 12 months prior to Screening, including mosaicplasty, microfracture, meniscectomy >50% or osteotomy
- Moderate to severe pain in the contralateral knee for the majority of days in the last 3 months prior to screening
- Malalignment >7.5? in the target knee (either varus or valgus)
- Any diagnosis of systemic inflammatory arthritis or connective tissue disease including but not limited to rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, gout, Paget's disease, systemic lupus erythematosus) or other systemic condition that might confound assessment of OA (e.g. fibromyalgia)
- lpsilateral hip OA or hip prosthesis recently implanted (within 1 year prior to screening) or hip replacement on either side planned within the study period
- other protocol-defined exclusion criteria may apply
Endpoint primari e secondari
Main Objective: - To assess the efficacy in regenerating articular cartilage tissue
- To assess the efficacy in relieving OA pain;Secondary Objective: - To assess the safety and tolerability
- To assess the potential immunogenicity
- To assess endogenous ANGPTL3, and PK
- To assess the efficacy in regenerating articular cartilage;
- To assess the efficacy in maintaining or regenerating articular cartilage
- To assess the efficacy on synovitis
- To assess the efficacy, in relieving OA pain and improving function over time
;Primary end point(s): - Change in cartilage volume in the index region measured by MRI
- Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain subscale;Timepoint(s) of evaluation of this end point: - Baseline to Day 197
- Baseline to Day 85 (ICTRP)
Timepoint(s) of evaluation of this end point: - Day 15, 43, 85, 197 and 365
- Day 1, 15, 43, 85, 197 and 365
- Day 1, 15, 43 and 71
- Day 1 and 43
- Day 1 and 43
- Day 1 and 43
- Baseline to Day 197 and 365
- Baseline to Day 197 and 365
- Baseline to Day 85
- Baseline to Day 15, 29, 43, 57, 71, 85, 197 and 365
- Baseline to Day 15, 29, 43, 57, 71, 85, 197 and 365
- Baseline to Day 15, 29, 43, 57, 71 85, 197 and 365
;Secondary end point(s): - Anti-LNA043 antibodies in serum
- ANGPTL3 serum concentrations
- ANGPTL3 synovial fluid concentrations
- LNA043 PK profile in serum (Cmax)
- LNA043 PK profile in serum (Tmax)
- LNA043 PK profile in serum (AUC)
- Change in cartilage volume of the index region measured by MRI
- Change in cartilage thickness of the index region measured by MRI
- Change in synovitis level measured from Ktrans by Dynamic Contrast Enhanced MRI (DCE-MRI)
- Change in numeric rating scale (NRS) Pain over time
- Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain subscale over time
- Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) Function in daily living (ADL) subscale over time (ICTRP)
Data di registrazione
10.06.2022 (ICTRP)
Inclusione del primo partecipante
24.08.2022 (ICTRP)
Sponsor secondari
non disponibile
Contatti aggiuntivi
Clinical Trial Information Desk, DRA.Estonia@novartis.com, +372 663 0810, SIA Novartis Baltics Estonian Branch (ICTRP)
ID secondari
CLNA043A12203, 2020-003631-21-DE (ICTRP)
Risultati-Dati individuali dei partecipanti
non disponibile
Ulteriori informazioni sullo studio
https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2020-003631-21 (ICTRP)
Risultati dello studio
Riepilogo dei risultati
non disponibile
Link ai risultati nel registro primario
non disponibile