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 will establish safety and efficacy of canakinumab and LNA043 in patients with knee osteoarthritis (OA).

Study Overview

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

• Study Type: Interventional
• Enrollment (Estimated): 138
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Novartis Pharmaceuticals; Phone Number: 1-888-669-6682; Email: novartis.email@novartis.com
• Study Contact Backup: Name: Novartis Pharmaceuticals; Phone Number: +41613241111

Study Locations

• China
  • Beijing, China, 100044
    • Withdrawn
    • Novartis Investigative Site
  • Beijing
    • Beijing, Beijing, China, 100044
      • Withdrawn
      • Novartis Investigative Site
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
      • Withdrawn
      • Novartis Investigative Site
  • Hubei
    • Wuhan, Hubei, China, 430022
      • Withdrawn
      • Novartis Investigative Site
  • Hunan
    • Zhuzhou, Hunan, China, 412000
      • Withdrawn
      • Novartis Investigative Site
  • Inner Mongolia
    • Hohhot, Inner Mongolia, China, 010017
      • Withdrawn
      • Novartis Investigative Site
• Czechia
  • Kolin, Czechia, 280 02
    • Active, not recruiting
    • Novartis Investigative Site
  • Uherske Hradiste, Czechia, 686 01
    • Withdrawn
    • Novartis Investigative Site
  • Czech Republic
    • Brno, Czech Republic, Czechia, 66250
      • Withdrawn
      • Novartis Investigative Site
    • Pardubice, Czech Republic, Czechia, 530 02
      • Withdrawn
      • Novartis Investigative Site
    • Praha, Czech Republic, Czechia, 19000
      • Completed
      • Novartis Investigative Site
• Estonia
  • Tallinn, Estonia, 10128
    • Withdrawn
    • Novartis Investigative Site
  • Tartu, Estonia, 50406
    • Active, not recruiting
    • Novartis Investigative Site
  • Tartu, Estonia, 50708
    • Withdrawn
    • Novartis Investigative Site
  • Harjumaa
    • Tallinn, Harjumaa, Estonia, 10617
      • Withdrawn
      • Novartis Investigative Site
• Germany
  • Bad Doberan, Germany, 18209
    • Withdrawn
    • Novartis Investigative Site
  • Berlin, Germany, 10117
    • Withdrawn
    • Novartis Investigative Site
  • Giessen, Germany, 35392
    • Withdrawn
    • Novartis Investigative Site
  • Herne, Germany, 44649
    • Withdrawn
    • Novartis Investigative Site
  • Muenster, Germany, 48149
    • Withdrawn
    • Novartis Investigative Site
• Hungary
  • Budapest, Hungary, 1036
    • Recruiting
    • Novartis Investigative Site
  • Gyor, Hungary, 9024
    • Withdrawn
    • Novartis Investigative Site
  • Zalaegerszeg, Hungary, 8900
    • Recruiting
    • Novartis Investigative Site
  • Bacs Kiskun
    • Kecskemet, Bacs Kiskun, Hungary, 6044
      • Recruiting
      • Novartis Investigative Site
  • Fejer
    • Szekesfehervar, Fejer, Hungary, 8000
      • Withdrawn
      • Novartis Investigative Site
• Latvia
  • Riga, Latvia, 1005
    • Active, not recruiting
    • Novartis Investigative Site
  • Riga, Latvia, LV-1005
    • Withdrawn
    • Novartis Investigative Site
• Lithuania
  • Kaunas, Lithuania, 44320
    • Withdrawn
    • Novartis Investigative Site
  • LTU
    • Vilnius, LTU, Lithuania, LT-08406
      • Withdrawn
      • Novartis Investigative Site
• Poland
  • Gliwice, Poland, 44100
    • Recruiting
    • Novartis Investigative Site
  • Krakow, Poland, 31-501
    • Recruiting
    • Novartis Investigative Site
  • Warszawa, Poland, 02 777
    • Active, not recruiting
    • Novartis Investigative Site
  • Warszawa, Poland, 00-215
    • Recruiting
    • Novartis Investigative Site
• Russian Federation
  • St Petersburg, Russian Federation, 190068
    • Withdrawn
    • Novartis Investigative Site
• Switzerland
  • Lausanne, Switzerland, 1011
    • Withdrawn
    • Novartis Investigative Site
  • St Gallen, Switzerland, CH 9007
    • Withdrawn
    • Novartis Investigative Site
• United States
  • California
    • La Mesa, California, United States, 91942
      • Active, not recruiting
      • Novartis Investigative Site
  • Florida
    • Clearwater, Florida, United States, 33765
      • Recruiting
      • Novartis Investigative Site
    • Sunrise, Florida, United States, 33351
      • Recruiting
      • Novartis Investigative Site
  • Kansas
    • Kansas City, Kansas, United States, 66160-7330
      • Withdrawn
      • Novartis Investigative Site
  • Nevada
    • Las Vegas, Nevada, United States, 89119
      • Recruiting
      • Novartis Investigative Site
  • North Carolina
    • Morehead City, North Carolina, United States, 28557
      • Recruiting
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 38 years to 78 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) ≥2 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: LNA043; Placebo to canakinumab + LNA043	Biological: LNA043; intra-articular injection (into the knee); Other: Placebo to canakinumab; intra-articular injection (into the knee)
Placebo Comparator: Placebo; Placebo to canakinumab	Other: Placebo to canakinumab; intra-articular injection (into the knee)
Experimental: canakinumab + LNA043	Biological: LNA043; intra-articular injection (into the knee); Biological: canakinumab; intra-articular injection (into the knee); Other Names: ACZ885
Experimental: canakinumab	Biological: canakinumab; intra-articular injection (into the knee); 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	Comparing LNA043 with no LNA043 treatment (Placebo) arms.	Baseline to Day 197
Change in Knee injury and Osteoarthritis Outcome Score (KOOS) Pain subscale	Comparing canakinumab with no canakinumab treatment (Placebo) arms. 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: Pain (9 questions), Symptoms (7 questions), Function in daily living (ADL) (17 questions), Function in sport and recreation (Sport/Rec) (5 questions) and knee related Quality of Life (QoL) (4 questions). On this scale, 100% indicates no problems and 0% indicates extreme problems.	Baseline to Day 85

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anti-LNA043 antibodies in serum		Day 15, 43, 85, 197 and 365
ANGPTL3 serum concentrations		Day 1, 15, 43, 85, 197 and 365
ANGPTL3 synovial fluid concentrations		Day 1, 15, 43 and 71
LNA043 PK profile in serum (Cmax)		Day 1 and 43
LNA043 PK profile in serum (Tmax)		Day 1 and 43
LNA043 PK profile in serum (AUC)		Day 1 and 43
Change in cartilage volume of the index region measured by MRI		Baseline to Day 197 and 365
Change in cartilage thickness of the index region measured by MRI		Baseline to Day 197 and 365
Change in synovitis level measured from Ktrans by Dynamic Contrast Enhanced MRI (DCE-MRI)		Baseline to Day 85
Change in numeric rating scale (NRS) Pain over time	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).	Baseline to Day 15, 29, 43, 57, 71, 85, 197 and 365
Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain subscale over time	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: Pain (9 questions), Symptoms (7 questions), Function in daily living (ADL) (17 questions), Function in sport and recreation (Sport/Rec) (5 questions) and knee related Quality of Life (QoL) (4 questions). On this scale, 100% indicates no problems and 0% indicates extreme problems.	Baseline to 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	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: Pain (9 questions), Symptoms (7 questions), Function in daily living (ADL) (17 questions), Function in sport and recreation (Sport/Rec) (5 questions) and knee related Quality of Life (QoL) (4 questions). On this scale, 100% indicates no problems and 0% indicates extreme problems.	Baseline to Day 15, 29, 43, 57, 71, 85, 197 and 365

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): August 27, 2021
• Primary Completion (Estimated): June 25, 2024
• Study Completion (Estimated): June 25, 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): February 1, 2024
• Last Update Submitted That Met QC Criteria: January 30, 2024
• Last Verified: January 1, 2024

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: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee; Physiological Effects of Drugs; Immunologic Factors; Antibodies, Monoclonal
• 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