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)

Knee Osteoarthritis Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04814368
• Other study ID #: CLNA043A12203
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: August 27, 2021
• Est. completion date: June 25, 2024

Study information

• Verified date: June 2024
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 24
• Est. completion date: June 25, 2024
• Est. primary completion date: June 25, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Knee Osteoarthritis
• Osteoarthritis
• Osteoarthritis, Knee

Intervention

Biological:
• canakinumab
intra-articular injection (into the knee)
• LNA043
intra-articular injection (into the knee)

Other:
• Placebo to canakinumab
intra-articular injection (into the knee)

Locations

Country	Name	City	State
Czechia	Novartis Investigative Site	Praha	Czech Republic
Estonia	Novartis Investigative Site	Tartu
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Kecskemet	Bacs Kiskun
Latvia	Novartis Investigative Site	Riga
Poland	Novartis Investigative Site	Warszawa
United States	Clinical Res. of W Florida	Clearwater	Florida
United States	Horizon Clinical Research	La Mesa	California
United States	LV Research	Las Vegas	Nevada
United States	Lucas Research .	Morehead City	North Carolina
United States	Precision Clinical Research LLC	Sunrise	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Czechia,  Estonia,  Hungary,  Latvia,  Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in cartilage volume in the index region measured by MRI	Comparing LNA043 with no LNA043 treatment (Placebo) arms.	Baseline to Day 197
Primary	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	Anti-LNA043 antibodies in serum		Day 15, 43, 85, 197 and 365
Secondary	ANGPTL3 serum concentrations		Day 1, 15, 43, 85, 197 and 365
Secondary	ANGPTL3 synovial fluid concentrations		Day 1, 15, 43 and 71
Secondary	LNA043 PK profile in serum (Cmax)		Day 1 and 43
Secondary	LNA043 PK profile in serum (Tmax)		Day 1 and 43
Secondary	LNA043 PK profile in serum (AUC)		Day 1 and 43
Secondary	Change in cartilage volume of the index region measured by MRI		Baseline to Day 197 and 365
Secondary	Change in cartilage thickness of the index region measured by MRI		Baseline to Day 197 and 365
Secondary	Change in synovitis level measured from Ktrans by Dynamic Contrast Enhanced MRI (DCE-MRI)		Baseline to Day 85
Secondary	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
Secondary	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
Secondary	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