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)

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04814368

Collaborator

(none)

138

Enrollment

Locations

Arms

31.6

Anticipated Duration (Months)

9.2

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Knee Osteoarthritis	Biological: canakinumab Biological: LNA043 Other: Placebo to canakinumab	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

138 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

Masking only applies to the canakinumab treatment. LNA043 treatment is open label.

Primary Purpose:

Treatment

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

Actual Study Start Date :

Aug 27, 2021

Anticipated Primary Completion Date :

Apr 15, 2024

Anticipated Study Completion Date :

Apr 15, 2024

Arms and Interventions

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 canakinumab + LNA043	Biological: canakinumab intra-articular injection (into the knee) Other Names: ACZ885 Biological: LNA043 intra-articular injection (into the knee)
Experimental: canakinumab canakinumab	Biological: canakinumab intra-articular injection (into the knee) Other Names: ACZ885

Outcome Measures

Primary Outcome Measures

Change in cartilage volume in the index region measured by MRI [Baseline to Day 197]
Comparing LNA043 with no LNA043 treatment (Placebo) arms.
Change in Knee injury and Osteoarthritis Outcome Score (KOOS) Pain subscale [Baseline to Day 85]
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 [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 [Baseline to Day 15, 29, 43, 57, 71, 85, 197 and 365]
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 [Baseline to Day 15, 29, 43, 57, 71, 85, 197 and 365]
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 [Baseline to Day 15, 29, 43, 57, 71, 85, 197 and 365]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years to 80 Years

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Clearwater	Florida	United States	33765
2	Novartis Investigative Site	Sunrise	Florida	United States	33351
3	Novartis Investigative Site	Las Vegas	Nevada	United States	89119
4	Novartis Investigative Site	Morehead City	North Carolina	United States	28557
5	Novartis Investigative Site	Beijing	Beijing	China	100044
6	Novartis Investigative Site	Guangzhou	Guangdong	China	510515
7	Novartis Investigative Site	Zhuzhou	Hunan	China
8	Novartis Investigative Site	Beijing		China	100044
9	Novartis Investigative Site	Pardubice	Czech Republic	Czechia	530 02
10	Novartis Investigative Site	Praha	Czech Republic	Czechia	19000
11	Novartis Investigative Site	Kolin		Czechia	280 02
12	Novartis Investigative Site	Uherske Hradiste		Czechia	686 01
13	Novartis Investigative Site	Herne		Germany	44649
14	Novartis Investigative Site	Szekesfehervar	Fejer	Hungary	8000
15	Novartis Investigative Site	St Petersburg		Russian Federation	190068