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)

NCT04814368 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: CLNA043A12203
• Study Type: interventional
• Target: 23
• Locations: 6 countries
• Sites: 11

Brief Summary

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

Conditions

Knee Osteoarthritis

Keywords

canakinumab; LNA043; knee; osteoarthritis; OA; joint pain; cartilage; MRI; DCE-MRI; KOOS; NRS Pain; IPAQ

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (17)

• Number of Participants With Anti-LNA043 Antibodies (Placebo to ACZ885+LNA043 Versus ACZ885 + LNA043)

  From pre-dose up to Day 365

• Maximum Serum Concentration (Cmax) of ANGPTL3 (Placebo to ACZ885+LNA043 Versus ACZ885+LNA043)

  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)

  Pre-dose on Days 1, 15, 43, and 71

• Maximum Serum Concentration (Cmax) of LNA043 (Placebo to ACZ885+LNA043 Versus ACZ885+LNA043)

  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)

  Day 15: pre-dose, 20, 60, 120 and 240 minutes, and 8 and 24 hours post LNA043 first injection on Day 15

Study Arms (4)

Placebo+LNA043

EXPERIMENTAL

Placebo to canakinumab on Day 1 followed by LNA043 on Days 15, 43 and 71

Biological: LNA043; Other: Placebo to canakinumab

Placebo

PLACEBO COMPARATOR

Placebo to canakinumab on Day 1

Other: Placebo to canakinumab

canakinumab + LNA043

EXPERIMENTAL

Canakinumab on Day 1 followed by LNA043 on Days 15, 43 and 71

Biological: canakinumab; Biological: LNA043

canakinumab

EXPERIMENTAL

Canakinumab on Day 1

Biological: canakinumab

Interventions

canakinumab BIOLOGICAL

Canakinumab 600 mg single intra-articular injection (into the knee) on Day 1

Also known as: ACZ885

canakinumab; canakinumab + LNA043

LNA043 BIOLOGICAL

LNA043 40 mg intra-articular injection (into the knee) every 4 weeks, on Days 15, 43 and 71

Placebo+LNA043; canakinumab + LNA043

Placebo to canakinumab OTHER

Placebo to canakinumab single intra-articular injection (into the knee) on Day 1

Placebo; Placebo+LNA043

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (11)

Horizon Clinical Research

La Mesa, California, 91942, United States

Location

Clinical Res Of W Florida

Clearwater, Florida, 33765, United States

Location

Precision Clinical Research LLC

Sunrise, Florida, 33351, United States

Location

LV Research

Las Vegas, Nevada, 89119, United States

Location

Lucas Research

Morehead City, North Carolina, 28557, United States

Location

Novartis Investigative Site

Prague, Czech Republic, 19000, Czechia

Location

Novartis Investigative Site

Tartu, 50406, Estonia

Location

Novartis Investigative Site

Kecskemét, Bács-Kiskun county, 6044, Hungary

Location

Novartis Investigative Site

Budapest, 1036, Hungary

Location

Novartis Investigative Site

Riga, 1005, Latvia

Location

Novartis Investigative Site

Warsaw, 02-677, Poland

Location

Related Links

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

MeSH Terms

Conditions

Osteoarthritis, Knee; Osteoarthritis; Arthralgia

Interventions

canakinumab

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

The small sample size overall and the difference in group sizes do not allow a valid interpretation of the data regarding efficacy, pharmacokinetics and immunogenicity.

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

novartis.email@novartis.com

+ 1 862 778 8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Masking only applies to the canakinumab treatment. LNA043 treatment is open label.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 22, 2021
• First Posted: March 24, 2021
• Study Start: August 27, 2021
• Primary Completion: June 24, 2024
• Study Completion: June 24, 2024
• Last Updated: October 24, 2025
• Results First Posted: July 30, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share

Locations

ES (1); US (5); HU (2); CZ (1); LA (1); PL (1)