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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)

Terminated Phase 2 Results posted Last updated 24 October 2025
What this trial tests

Phase 2 trial testing canakinumab in Knee Osteoarthritis in 23 participants. Terminated before completion.

Timeline
27 August 2021
Primary endpoint
24 June 2024
24 June 2024

Quick facts

Lead sponsorNovartis Pharmaceuticals
PhasePhase 2
StatusTerminated
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment23
Start date27 August 2021
Primary completion24 June 2024
Estimated completion24 June 2024
Sites11 locations across Estonia, Hungary, Poland, Czechia, United States, Latvia

Drugs / interventions tested

Conditions studied

Sponsor

Novartis Pharmaceuticals — full company profile →

Who can join

Adults 40 to 80, any sex, with Knee Osteoarthritis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change in Cartilage Volume in the Index Region Measured by MRI at Day 197 (Placebo to ACZ885+LNA043 Versus Placebo to ACZ885) Primary · Baseline, Day 197

Magnetic resonance images (MRI) were obtained from the target knee to visualize and quantify changes in volume of cartilage in the index region. The index region was defined as the union of the femoral medial anterior (FMA), central (FMC) and posterior (FMP) cartilage subregions in the knee.

GroupValue95% CI
Placebo to ACZ885+LNA043 40 mg108.33± 226.451
Placebo to ACZ885-26.13± 65.204
Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain Subscale (ACZ885 Versus Placebo to ACZ885) Primary · Baseline, Day 85

The KOOS questionnaire is a commonly used instrument to assess the patient's perception about their knee and associated problems. The original KOOS consists of 5 subscales. One of those is the KOOS pain consisting of 9 questions with a recall of 7days. Each question has 5 standardized answer options with a score from 0 to 4. A normalized score (100 indicating no symptoms and 0 indicating extreme symptoms) is calculated for each subscale.

GroupValue95% CI
ACZ885 600 mg22.2± 20.09
Placebo to ACZ88513.9± 13.89
Number of Participants With Anti-LNA043 Antibodies (Placebo to ACZ885+LNA043 Versus ACZ885 + LNA043) Secondary · From pre-dose up to Day 365

To evaluate the immunogenicity of LNA043 via validated ligand-binding assay of potential anti-LNA043 antibodies.

GroupValue95% CI
Placebo to ACZ885+LNA043 40 mg0
ACZ885 600 mg + LNA043 40 mg0
Maximum Serum Concentration (Cmax) of ANGPTL3 (Placebo to ACZ885+LNA043 Versus ACZ885+LNA043) Secondary · Pre-dose Day 1, Day 15, Day 43 and 60 minutes after first injection of LNA043 on Day 15

ANGPTL3 is a protein that is primarily involved in the lipid metabolism but has recently been shown to have chondrogenic and chondroprotective effects. Cmax is defined as the maximum (peak) observed concentration following a dose. ANGPTL3 serum concentrations were determined using the actual recorded sampling times and non-compartmental method with Phoenix WinNonlin (Version 8 or higher). ANGPTL3 was determined by a validated ligand binding assay; the anticipated LLOQ is 39.7 pmol/L in serum.

GroupValue95% CI
Placebo to ACZ885+LNA043 40 mg16.2± 2.47
ACZ885 600 mg + LNA043 40 mg24.1± 7.32
Synovial Fluid Concentrations of ANGPTL3 (Placebo to ACZ885+LNA043 Versus ACZ885+LNA043) Secondary · Pre-dose on Days 1, 15, 43, and 71

ANGPTL3 is a protein that is primarily involved in the lipid metabolism but has recently been shown to have chondrogenic and chondroprotective effects. ANGPTL3 was measured in synovial fluid.

Day 1
GroupValue95% CI
Placebo to ACZ885+LNA043 40 mgNA± NA
ACZ885 600 mg + LNA043 40 mgNA± NA
Day 15
GroupValue95% CI
Placebo to ACZ885+LNA043 40 mgNA± NA
ACZ885 600 mg + LNA043 40 mgNA± NA
Day 43
GroupValue95% CI
Placebo to ACZ885+LNA043 40 mgNA± NA
ACZ885 600 mg + LNA043 40 mgNA± NA
Day 71
GroupValue95% CI
Placebo to ACZ885+LNA043 40 mgNA± NA
ACZ885 600 mg + LNA043 40 mgNA± NA
Maximum Serum Concentration (Cmax) of LNA043 (Placebo to ACZ885+LNA043 Versus ACZ885+LNA043) Secondary · Day 15: pre-dose, 20, 60, 120 and 240 minutes, and 8 and 24 hours post LNA043 first injection on Day 15

Cmax is defined as the maximum (peak) observed concentration following a dose. LNA043 serum concentrations were determined using the actual recorded sampling times and non-compartmental method with Phoenix WinNonlin (Version 8 or higher). LNA043 was determined by a validated immuno-capture and LC-MS/MS method; the anticipated LLOQ is 10 ng/mL in serum.

GroupValue95% CI
Placebo to ACZ885+LNA043 40 mg120
ACZ885 600 mg + LNA043 40 mg149
Time to Reach Maximum Serum Concentration (Tmax) of LNA043 (Placebo to ACZ885+LNA043 Versus ACZ885+LNA043) Secondary · Day 15: pre-dose, 20, 60, 120 and 240 minutes, and 8 and 24 hours post LNA043 first injection on Day 15

Tmax is the time to reach maximum (peak) drug concentration after single-dose administration (time). LNA043 serum concentrations were determined using the actual recorded sampling times and non-compartmental method with Phoenix WinNonlin (Version 8 or higher). LNA043 was determined by a validated immuno-capture and LC-MS/MS method; the anticipated LLOQ is 10 ng/mL in serum.

GroupValue95% CI
Placebo to ACZ885+LNA043 40 mg2
ACZ885 600 mg + LNA043 40 mg4.02
Area Under Serum Concentration-time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of LNA043 (Placebo to ACZ885+LNA043 Versus ACZ885+LNA043) Secondary · Day 15: pre-dose, 20, 60, 120 and 240 minutes, and 8 and 24 hours post LNA043 first injection on Day 15

AUClast is the area under the serum concentration-time curve from time zero to the time of last quantifiable concentration (tlast) of LNA043. LNA043 serum concentrations were determined using the actual recorded sampling times and non-compartmental method with Phoenix WinNonlin (Version 8 or higher). LNA043 was determined by a validated immuno-capture and LC-MS/MS method; the anticipated LLOQ is 10 ng/mL in serum.

GroupValue95% CI
Placebo to ACZ885+LNA043 40 mg800
ACZ885 600 mg + LNA043 40 mg1880
Change in Cartilage Volume of the Index Region Measured by MRI at Day 197 and Day 365 (ACZ885+LNA043 Versus ACZ885, and ACZ885+LNA043 Versus Placebo to ACZ885+LNA043) Secondary · Baseline, Day 197 and Day 365

Magnetic resonance images (MRI) were obtained from the target knee to visualize and quantify changes in volume of cartilage in the index region. The index region was defined as the union of the femoral medial anterior (FMA), central (FMC) and posterior (FMP) cartilage subregions in the knee.

Day 197
GroupValue95% CI
Placebo to ACZ885+LNA043 40 mg108.33± 226.451
ACZ885 600 mg + LNA043 40 mg307.90± 580.213
ACZ885 600 mg-82.33± 390.645
Day 365
GroupValue95% CI
Placebo to ACZ885+LNA043 40 mg152.78± 135.128
ACZ885 600 mg + LNA043 40 mg20.54± 557.708
ACZ885 600 mg-129.93± 544.793
Change in Cartilage Volume of the Index Region Measured by MRI at Day 365 (Placebo to ACZ885+LNA043 Versus Placebo to ACZ885) Secondary · Baseline, Day 365

Magnetic resonance images (MRI) were obtained from the target knee to visualize and quantify changes in volume of cartilage in the index region. The index region was defined as the union of the femoral medial anterior (FMA), central (FMC) and posterior (FMP) cartilage subregions in the knee.

GroupValue95% CI
Placebo to ACZ885+LNA043 40 mg152.78± 135.128
Placebo to ACZ88520.54± 557.708
Change in Cartilage Thickness of the Index Region Measured by MRI at Day 197 and Day 365 (ACZ885+LNA043 Versus ACZ885, and ACZ885+LNA043 Versus Placebo to ACZ885+LNA043) Secondary · Baseline, Day 197 and 365

Magnetic resonance images (MRI) were obtained from the target knee to visualize and quantify changes in thickness of cartilage in the index region. The index region was defined as the union of the femoral medial anterior (FMA), central (FMC) and posterior (FMP) cartilage subregions in the knee.

Day 197
GroupValue95% CI
Placebo to ACZ885+LNA043 40 mg0.07± 0.083
ACZ885 600 mg + LNA043 40 mg0.13± 0.212
ACZ885 600 mg-0.02± 0.121
Day 365
GroupValue95% CI
Placebo to ACZ885+LNA043 40 mg-0.03± 0.046
ACZ885 600 mg + LNA043 40 mg0.04± 0.168
ACZ885 600 mg-0.05± 0.152
Change in Cartilage Thickness of the Index Region Measured by MRI at Day 197 and Day 365 (Placebo to ACZ885+LNA043 Versus Placebo to ACZ885) Secondary · Baseline, Day 197 and 365

Magnetic resonance images (MRI) were obtained from the target knee to visualize and quantify changes in thickness of cartilage in the index region. The index region was defined as the union of the femoral medial anterior (FMA), central (FMC) and posterior (FMP) cartilage subregions in the knee.

Day 197
GroupValue95% CI
Placebo to ACZ885+LNA043 40 mg0.07± 0.083
Placebo to ACZ8850.06± 0.112
Day 365
GroupValue95% CI
Placebo to ACZ885+LNA043 40 mg-0.03± 0.046
Placebo to ACZ8850.11± 0.072

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period, up to a maximum duration of approximately 52 weeks.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo to ACZ885+LNA043 40 mg
Serious: 0/3 (0%)
Deaths: 0/3
Placebo to ACZ885
Serious: 0/9 (0%)
Deaths: 0/9
ACZ885 600 mg + LNA043 40 mg
Serious: 0/3 (0%)
Deaths: 0/3
ACZ885 600 mg
Serious: 0/8 (0%)
Deaths: 0/8
Total
Serious: 0/23 (0%)
Deaths: 0/23
Other adverse events (12 terms — click to expand)

ReactionSystemPlacebo to ACZ885+LNA043 4…Placebo to ACZ885ACZ885 600 mg + LNA043 40 mgACZ885 600 mgTotal
Bundle branch block rightCardiac disorders
Abscess limbInfections and infestations
Body tineaInfections and infestations
COVID-19Infections and infestations
NasopharyngitisInfections and infestations
Oral herpesInfections and infestations
RhinitisInfections and infestations
Upper respiratory tract infectionInfections and infestations
Urinary tract infectionInfections and infestations
Blood creatine phosphokinase increasedInvestigations
HypophosphataemiaMetabolism and nutrition disorders
CoughRespiratory, thoracic and mediastinal disorders

Data from ClinicalTrials.gov NCT04814368 adverse events section.

Sponsor's own description

The study was established to show safety and efficacy of canakinumab and LNA043 in patients with knee osteoarthritis (OA).

Publications & conference data

7 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Osteoarthritis: pathogenic signaling pathways and therapeutic targets.
    Yao Q, Wu X, Tao C, Gong W, et al · · 2023 · cited 730× · PMID 36737426 · DOI 10.1038/s41392-023-01330-w
  2. Angiopoietin-like 3-derivative LNA043 for cartilage regeneration in osteoarthritis: a randomized phase 1 trial.
    Gerwin N, Scotti C, Halleux C, Fornaro M, et al · · 2022 · cited 50× · PMID 36456835 · DOI 10.1038/s41591-022-02059-9
  3. Alternative Routes of Administration for Therapeutic Antibodies-State of the Art.
    Pitiot A, Heuzé-Vourc'h N, Sécher T. · · 2022 · cited 45× · PMID 36134952 · DOI 10.3390/antib11030056
  4. Therapeutic antibodies - natural and pathological barriers and strategies to overcome them.
    Al Ojaimi Y, Blin T, Lamamy J, Gracia M, et al · · 2022 · cited 27× · PMID 34687769 · DOI 10.1016/j.pharmthera.2021.108022
  5. Bioactive peptides and proteins for tissue repair: microenvironment modulation, rational delivery, and clinical potential.
    Hao ZW, Zhang ZY, Wang ZP, Wang Y, et al · · 2024 · cited 24× · PMID 39639374 · DOI 10.1186/s40779-024-00576-x
  6. Advances and Challenges in the Pursuit of Disease-Modifying Osteoarthritis Drugs: A Review of 2010-2024 Clinical Trials.
    Brandt MD, Malone JB, Kean TJ. · · 2025 · cited 19× · PMID 40002768 · DOI 10.3390/biomedicines13020355
  7. Antibody and aptamer-based therapies for osteoarthritis: Application of antibodies and promise of aptamers.
    Chen H, Ye Z, Korpershoek JV, Creemers LB, et al · · 2025 · cited 2× · PMID 40487355 · DOI 10.1016/j.omtn.2025.102552

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Other trials of canakinumab

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Other Novartis Pharmaceuticals trials

Trials by the same sponsor.

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing