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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)

Phase 2
Terminated
Conditions
Knee Osteoarthritis
Interventions
Biological: LNA043
Biological: canakinumab
Other: Placebo to canakinumab
Registration Number
NCT04814368
Lead Sponsor
Novartis Pharmaceuticals
Brief Summary

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

Detailed Description

Not available

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
23
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)
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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
Read More

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
LNA043LNA043Placebo to canakinumab + LNA043
LNA043Placebo to canakinumabPlacebo to canakinumab + LNA043
canakinumab + LNA043LNA043canakinumab + LNA043
PlaceboPlacebo to canakinumabPlacebo to canakinumab
canakinumab + LNA043canakinumabcanakinumab + LNA043
canakinumabcanakinumabcanakinumab
Primary Outcome Measures
NameTimeMethod
Change in cartilage volume in the index region measured by MRIBaseline to Day 197

Comparing LNA043 with no LNA043 treatment (Placebo) arms.

Change in Knee injury and Osteoarthritis Outcome Score (KOOS) Pain subscaleBaseline 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
NameTimeMethod
ANGPTL3 synovial fluid concentrationsDay 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
Anti-LNA043 antibodies in serumDay 15, 43, 85, 197 and 365
ANGPTL3 serum concentrationsDay 1, 15, 43, 85, 197 and 365
Change in cartilage volume of the index region measured by MRIBaseline to Day 197 and 365
Change in cartilage thickness of the index region measured by MRIBaseline 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 Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain subscale over timeBaseline 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 numeric rating scale (NRS) Pain over timeBaseline 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) Function in daily living (ADL) subscale over timeBaseline 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.

Trial Locations

Locations (6)

LV Research

🇺🇸

Las Vegas, Nevada, United States

Clinical Res Of W Florida

🇺🇸

Clearwater, Florida, United States

Horizon Clinical Research

🇺🇸

La Mesa, California, United States

Novartis Investigative Site

🇵🇱

Warszawa, Poland

Lucas Research .

🇺🇸

Morehead City, North Carolina, United States

Precision Clinical Research LLC

🇺🇸

Sunrise, Florida, United States

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