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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)

Primary Purpose

Knee Osteoarthritis

Status
Recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
canakinumab
LNA043
Placebo to canakinumab
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Knee Osteoarthritis focused on measuring canakinumab, LNA043, knee, osteoarthritis, OA, joint pain, cartilage, MRI, DCE-MRI, KOOS, NRS Pain, IPAQ

Eligibility Criteria

40 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative Site
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative Site
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Placebo Comparator

Experimental

Experimental

Arm Label

LNA043

Placebo

canakinumab + LNA043

canakinumab

Arm Description

Placebo to canakinumab + LNA043

Placebo to canakinumab

canakinumab + LNA043

canakinumab

Outcomes

Primary Outcome Measures

Change in cartilage volume in the index region measured by MRI
Comparing LNA043 with no LNA043 treatment (Placebo) arms.
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.

Secondary Outcome Measures

Anti-LNA043 antibodies in serum
ANGPTL3 serum concentrations
ANGPTL3 synovial fluid concentrations
LNA043 PK profile in serum (Cmax)
LNA043 PK profile in serum (Tmax)
LNA043 PK profile in serum (AUC)
Change in cartilage volume of the index region measured by MRI
Change in cartilage thickness of the index region measured by MRI
Change in synovitis level measured from Ktrans by Dynamic Contrast Enhanced MRI (DCE-MRI)
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).
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.
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.

Full Information

First Posted
March 22, 2021
Last Updated
October 23, 2023
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT04814368
Brief Title
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

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 27, 2021 (Actual)
Primary Completion Date
October 17, 2025 (Anticipated)
Study Completion Date
October 17, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Knee Osteoarthritis
Keywords
canakinumab, LNA043, knee, osteoarthritis, OA, joint pain, cartilage, MRI, DCE-MRI, KOOS, NRS Pain, IPAQ

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Masking only applies to the canakinumab treatment. LNA043 treatment is open label.
Allocation
Randomized
Enrollment
138 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
LNA043
Arm Type
Experimental
Arm Description
Placebo to canakinumab + LNA043
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo to canakinumab
Arm Title
canakinumab + LNA043
Arm Type
Experimental
Arm Description
canakinumab + LNA043
Arm Title
canakinumab
Arm Type
Experimental
Arm Description
canakinumab
Intervention Type
Biological
Intervention Name(s)
canakinumab
Other Intervention Name(s)
ACZ885
Intervention Description
intra-articular injection (into the knee)
Intervention Type
Biological
Intervention Name(s)
LNA043
Intervention Description
intra-articular injection (into the knee)
Intervention Type
Other
Intervention Name(s)
Placebo to canakinumab
Intervention Description
intra-articular injection (into the knee)
Primary Outcome Measure Information:
Title
Change in cartilage volume in the index region measured by MRI
Description
Comparing LNA043 with no LNA043 treatment (Placebo) arms.
Time Frame
Baseline to Day 197
Title
Change in Knee injury and Osteoarthritis Outcome Score (KOOS) Pain subscale
Description
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.
Time Frame
Baseline to Day 85
Secondary Outcome Measure Information:
Title
Anti-LNA043 antibodies in serum
Time Frame
Day 15, 43, 85, 197 and 365
Title
ANGPTL3 serum concentrations
Time Frame
Day 1, 15, 43, 85, 197 and 365
Title
ANGPTL3 synovial fluid concentrations
Time Frame
Day 1, 15, 43 and 71
Title
LNA043 PK profile in serum (Cmax)
Time Frame
Day 1 and 43
Title
LNA043 PK profile in serum (Tmax)
Time Frame
Day 1 and 43
Title
LNA043 PK profile in serum (AUC)
Time Frame
Day 1 and 43
Title
Change in cartilage volume of the index region measured by MRI
Time Frame
Baseline to Day 197 and 365
Title
Change in cartilage thickness of the index region measured by MRI
Time Frame
Baseline to Day 197 and 365
Title
Change in synovitis level measured from Ktrans by Dynamic Contrast Enhanced MRI (DCE-MRI)
Time Frame
Baseline to Day 85
Title
Change in numeric rating scale (NRS) Pain over time
Description
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).
Time Frame
Baseline to Day 15, 29, 43, 57, 71, 85, 197 and 365
Title
Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain subscale over time
Description
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.
Time Frame
Baseline to Day 15, 29, 43, 57, 71, 85, 197 and 365
Title
Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) Function in daily living (ADL) subscale over time
Description
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.
Time Frame
Baseline to Day 15, 29, 43, 57, 71, 85, 197 and 365

10. Eligibility

Sex
All
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
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) ≥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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Novartis Pharmaceuticals
Phone
1-888-669-6682
Email
novartis.email@novartis.com
First Name & Middle Initial & Last Name or Official Title & Degree
Novartis Pharmaceuticals
Phone
+41613241111
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
La Mesa
State/Province
California
ZIP/Postal Code
91942
Country
United States
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Clearwater
State/Province
Florida
ZIP/Postal Code
33765
Country
United States
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Sunrise
State/Province
Florida
ZIP/Postal Code
33351
Country
United States
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160-7330
Country
United States
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89119
Country
United States
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Morehead City
State/Province
North Carolina
ZIP/Postal Code
28557
Country
United States
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100044
Country
China
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510515
Country
China
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Wuhan
State/Province
Hubei
ZIP/Postal Code
430022
Country
China
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Zhuzhou
State/Province
Hunan
ZIP/Postal Code
412000
Country
China
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Hohhot
State/Province
Inner Mongolia
ZIP/Postal Code
010017
Country
China
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Beijing
ZIP/Postal Code
100044
Country
China
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Brno
State/Province
Czech Republic
ZIP/Postal Code
66250
Country
Czechia
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Pardubice
State/Province
Czech Republic
ZIP/Postal Code
530 02
Country
Czechia
Individual Site Status
Withdrawn
Facility Name
Novartis Investigative Site
City
Praha
State/Province
Czech Republic
ZIP/Postal Code
19000
Country
Czechia
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Kolin
ZIP/Postal Code
280 02
Country
Czechia
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Uherske Hradiste
ZIP/Postal Code
686 01
Country
Czechia
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Tallinn
State/Province
Harjumaa
ZIP/Postal Code
10617
Country
Estonia
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Tallinn
ZIP/Postal Code
10128
Country
Estonia
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Tartu
ZIP/Postal Code
50406
Country
Estonia
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Bad Doberan
ZIP/Postal Code
18209
Country
Germany
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Giessen
ZIP/Postal Code
35392
Country
Germany
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Herne
ZIP/Postal Code
44649
Country
Germany
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Muenster
ZIP/Postal Code
48149
Country
Germany
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Kecskemet
State/Province
Bacs Kiskun
ZIP/Postal Code
6044
Country
Hungary
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Szekesfehervar
State/Province
Fejer
ZIP/Postal Code
8000
Country
Hungary
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Budapest
ZIP/Postal Code
1036
Country
Hungary
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Gyor
ZIP/Postal Code
9024
Country
Hungary
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Zalaegerszeg
ZIP/Postal Code
8900
Country
Hungary
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Riga
ZIP/Postal Code
1005
Country
Latvia
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Riga
ZIP/Postal Code
LV-1005
Country
Latvia
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Vilnius
State/Province
LTU
ZIP/Postal Code
LT-08406
Country
Lithuania
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Kaunas
ZIP/Postal Code
44320
Country
Lithuania
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Gliwice
ZIP/Postal Code
44100
Country
Poland
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Warszawa
ZIP/Postal Code
02 777
Country
Poland
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
St Petersburg
ZIP/Postal Code
190068
Country
Russian Federation
Individual Site Status
Withdrawn
Facility Name
Novartis Investigative Site
City
Lausanne
ZIP/Postal Code
1011
Country
Switzerland
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
St Gallen
ZIP/Postal Code
CH 9007
Country
Switzerland
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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

Learn more about this trial

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)

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