Clinical trial NCT04814368: 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)
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Knee Osteoarthritis
Keywords: canakinumab
LNA043
knee
osteoarthritis
OA
joint pain
cartilage
MRI
DCE-MRI
KOOS
NRS Pain
IPAQ
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2021-03-24
Enrollment: 23
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The study will establish safety and efficacy of canakinumab and LNA043 in patients with knee osteoarthritis (OA).


Eligibility criteria: 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)

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)
* Ipsilateral hip OA or hip prosthesis recently implanted (within 1 year prior to screening) or hip replacement on either side planned within the study period

Primary outcomes:
measure: Change in cartilage volume in the index region measured by MRI
timeFrame: Baseline to Day 197
measure: Change in Knee injury and Osteoarthritis Outcome Score (KOOS) Pain subscale
timeFrame: Baseline to Day 85
Secondary outcomes:
measure: Anti-LNA043 antibodies in serum
timeFrame: Day 15, 43, 85, 197 and 365
measure: ANGPTL3 serum concentrations
timeFrame: Day 1, 15, 43, 85, 197 and 365
measure: ANGPTL3 synovial fluid concentrations
timeFrame: Day 1, 15, 43 and 71
measure: LNA043 PK profile in serum (Cmax)
timeFrame: Day 1 and 43
measure: LNA043 PK profile in serum (Tmax)
timeFrame: Day 1 and 43
measure: LNA043 PK profile in serum (AUC)
timeFrame: Day 1 and 43
measure: Change in cartilage volume of the index region measured by MRI
timeFrame: Baseline to Day 197 and 365
measure: Change in cartilage thickness of the index region measured by MRI
timeFrame: Baseline to Day 197 and 365
measure: Change in synovitis level measured from Ktrans by Dynamic Contrast Enhanced MRI (DCE-MRI)
timeFrame: Baseline to Day 85
measure: Change in numeric rating scale (NRS) Pain over time
timeFrame: Baseline to Day 15, 29, 43, 57, 71, 85, 197 and 365
measure: Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain subscale over time
timeFrame: Baseline to Day 15, 29, 43, 57, 71, 85, 197 and 365
measure: Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) Function in daily living (ADL) subscale over time
timeFrame: Baseline to Day 15, 29, 43, 57, 71, 85, 197 and 365
Other outcomes:
Locations:
city: La Mesa
country: United States
facility: Horizon Clinical Research
state: California
city: Clearwater
country: United States
facility: Clinical Res Of W Florida
state: Florida
city: Sunrise
country: United States
facility: Precision Clinical Research LLC
state: Florida
city: Las Vegas
country: United States
facility: LV Research
state: Nevada
city: Morehead City
country: United States
facility: Lucas Research .
state: North Carolina
city: Praha
country: Czechia
facility: Novartis Investigative Site
state: Czech Republic
city: Tartu
country: Estonia
facility: Novartis Investigative Site
city: Kecskemet
country: Hungary
facility: Novartis Investigative Site
state: Bacs Kiskun
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Riga
country: Latvia
facility: Novartis Investigative Site
city: Warszawa
country: Poland
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: