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)

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

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

Study Overview

• Status: Terminated
• Conditions: Knee Osteoarthritis
• Intervention / Treatment: Biological: LNA043; Other: Placebo to canakinumab; Biological: canakinumab

Detailed Description

This was a non-confirmatory, randomized, four arm, placebo-controlled, participant-, investigator and sponsor-blinded study in participants with symptomatic knee OA with synovial inflammation.

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 2

Contacts and Locations

Study Locations

• Czechia
  • Czech Republic
    • Prague, Czech Republic, Czechia, 19000
      • Novartis Investigative Site
• Estonia
  • Tartu, Estonia, 50406
    • Novartis Investigative Site
• Hungary
  • Budapest, Hungary, 1036
    • Novartis Investigative Site
  • Bács-Kiskun county
    • Kecskemét, Bács-Kiskun county, Hungary, 6044
      • Novartis Investigative Site
• Latvia
  • Riga, Latvia, 1005
    • Novartis Investigative Site
• Poland
  • Warsaw, Poland, 02-677
    • Novartis Investigative Site
• United States
  • California
    • La Mesa, California, United States, 91942
      • Horizon Clinical Research
  • Florida
    • Clearwater, Florida, United States, 33765
      • Clinical Res Of W Florida
    • Sunrise, Florida, United States, 33351
      • Precision Clinical Research LLC
  • Nevada
    • Las Vegas, Nevada, United States, 89119
      • LV Research
  • North Carolina
    • Morehead City, North Carolina, United States, 28557
      • Lucas Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 36 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Placebo+LNA043; Placebo to canakinumab on Day 1 followed by LNA043 on Days 15, 43 and 71	Biological: LNA043; LNA043 40 mg intra-articular injection (into the knee) every 4 weeks, on Days 15, 43 and 71; Other: Placebo to canakinumab; Placebo to canakinumab single intra-articular injection (into the knee) on Day 1
Placebo Comparator: Placebo; Placebo to canakinumab on Day 1	Other: Placebo to canakinumab; Placebo to canakinumab single intra-articular injection (into the knee) on Day 1
Experimental: canakinumab + LNA043; Canakinumab on Day 1 followed by LNA043 on Days 15, 43 and 71	Biological: LNA043; LNA043 40 mg intra-articular injection (into the knee) every 4 weeks, on Days 15, 43 and 71; Biological: canakinumab; Canakinumab 600 mg single intra-articular injection (into the knee) on Day 1; Other Names: ACZ885
Experimental: canakinumab; Canakinumab on Day 1	Biological: canakinumab; Canakinumab 600 mg single intra-articular injection (into the knee) on Day 1; Other Names: ACZ885

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Cartilage Volume in the Index Region Measured by MRI at Day 197 (Placebo to ACZ885+LNA043 Versus Placebo to ACZ885)	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.	Baseline, Day 197
Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain Subscale (ACZ885 Versus Placebo to ACZ885)	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.	Baseline, Day 85

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Anti-LNA043 Antibodies (Placebo to ACZ885+LNA043 Versus ACZ885 + LNA043)	To evaluate the immunogenicity of LNA043 via validated ligand-binding assay of potential anti-LNA043 antibodies.	From pre-dose up to Day 365
Maximum Serum Concentration (Cmax) of ANGPTL3 (Placebo to ACZ885+LNA043 Versus ACZ885+LNA043)	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.	Pre-dose Day 1, Day 15, Day 43 and 60 minutes after first injection of LNA043 on Day 15
Synovial Fluid Concentrations of ANGPTL3 (Placebo to ACZ885+LNA043 Versus ACZ885+LNA043)	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.	Pre-dose on Days 1, 15, 43, and 71
Maximum Serum Concentration (Cmax) of LNA043 (Placebo to ACZ885+LNA043 Versus ACZ885+LNA043)	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.	Day 15: pre-dose, 20, 60, 120 and 240 minutes, and 8 and 24 hours post LNA043 first injection on Day 15
Time to Reach Maximum Serum Concentration (Tmax) of LNA043 (Placebo to ACZ885+LNA043 Versus ACZ885+LNA043)	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.	Day 15: pre-dose, 20, 60, 120 and 240 minutes, and 8 and 24 hours post LNA043 first injection on Day 15
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)	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.	Day 15: pre-dose, 20, 60, 120 and 240 minutes, and 8 and 24 hours post LNA043 first injection on Day 15
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)	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.	Baseline, Day 197 and Day 365
Change in Cartilage Volume of the Index Region Measured by MRI at Day 365 (Placebo to ACZ885+LNA043 Versus Placebo to ACZ885)	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.	Baseline, Day 365
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)	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.	Baseline, Day 197 and 365
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)	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.	Baseline, Day 197 and 365
Change in Synovitis Level Measured From Ktrans by Dynamic Contrast Enhanced MRI (DCE-MRI) (ACZ885 Versus Placebo to ACZ885)	Magnetic resonance images (MRI) were obtained from the target knee with dynamic contrast enhancement (DCE) to visualize and quantify changes in k-trans as a marker of the activity of synovial inflammation. During the DCE-MRI acquisition, while the contrast agent is preferentially taken up at sites with an increased perfusion due to the formation of new vessels with high porosity (such as the inflamed synovial membrane), a temporal variation of the MRI signal intensity occurs. When the contrast distributes through the intravascular and extravascular spaces, the MR signal intensity in the image volume elements (voxels) of the target tissue changes over time, generating so-called signal intensity (SI) curves. These curves can then be analyzed to derive parameters related to tissue perfusion. The parameter of primary interest was the volume transfer rate of the gadolinium-based contrast agent (GBCA) from the blood plasma in synovium, commonly referred to as Ktrans.	Baseline, Day 85
Change in Numeric Rating Scale (NRS) Over Time (ACZ885 Versus Placebo to ACZ885)	The Numerical Rating Scale (NRS) Pain is a subjective assessment in which individuals rate their pain on an eleven-point numerical scale. The scale ranges from 0 (no pain) to 10 (worst possible pain). The NRS Pain instrument had a recall period of 24 hours and the participants were asked to rate the pain intensity at its worst.	Baseline, Day 15, 29, 43, 57, 71, 85
Change in Numeric Rating Scale (NRS) Over Time (ACZ885+LNA043 Versus ACZ885, and ACZ885+LNA043 Versus Placebo to ACZ885+LNA043)	The Numerical Rating Scale (NRS) Pain is a subjective assessment in which individuals rate their pain on an eleven-point numerical scale. The scale ranges from 0 (no pain) to 10 (worst possible pain). The NRS Pain instrument had a recall period of 24 hours and the participants were asked to rate the pain intensity at its worst.	Baseline, Day 15, 29, 43, 57, 71, 85, 197 and 365
Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain Subscale Over Time (ACZ885 Versus Placebo to ACZ885)	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.	Baseline, Day 15, 29, 43, 57, 71, 85
Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain Subscale Over Time (ACZ885+LNA043 Versus ACZ885, and ACZ885+LNA043 Versus Placebo to ACZ885+LNA043)	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.	Baseline, Day 15, 29, 43, 57, 71, 85, 197 and 365
Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) Function in Daily Living (ADL) Subscale Over Time (ACZ885 Versus Placebo to ACZ885)	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 Function in Daily Living (ADL) subscale consisting of 17 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.	Baseline, Day 15, 29, 43, 57, 71, 85
Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) Function in Daily Living (ADL) Subscale Over Time (ACZ885+LNA043 Versus ACZ885, and ACZ885+LNA043 Versus Placebo to ACZ885+LNA043)	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 Function in Daily Living (ADL) subscale consisting of 17 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.	Baseline, Day 15, 29, 43, 57, 71, 85, 197 and 365

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• A Plain Language Trial Summary is available on www.novctrd.com

Study record dates

Study Major Dates

• Study Start (Actual): August 27, 2021
• Primary Completion (Actual): June 24, 2024
• Study Completion (Actual): June 24, 2024

Study Registration Dates

• First Submitted: March 22, 2021
• First Submitted That Met QC Criteria: March 22, 2021
• First Posted (Actual): March 24, 2021

Study Record Updates

• Last Update Posted (Estimated): October 24, 2025
• Last Update Submitted That Met QC Criteria: October 8, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: MRI; osteoarthritis; joint pain; knee; cartilage; KOOS; OA; DCE-MRI; canakinumab; LNA043; NRS Pain; IPAQ
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Musculoskeletal Diseases; Arthritis; Joint Diseases; Rheumatic Diseases; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Osteoarthritis; Osteoarthritis, Knee; Arthralgia; Immunologic Factors; Physiological Effects of Drugs; canakinumab
• Other Study ID Numbers: CLNA043A12203

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the study in line with applicable laws and regulations.

This study data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No