What is the mechanism of action of this treatment?

Common treatments for osteoarthritis (OA) often focus on reducing inflammation and promoting cartilage regeneration. Canakinumab, a monoclonal antibody targeting interleukin-1 beta (IL-1β), reduces inflammation by inhibiting this pro-inflammatory cytokine, potentially slowing joint degradation. LNA043 aims to stimulate cartilage regeneration, addressing the cartilage loss that characterizes OA. These mechanisms are important for OA patients as they offer a dual approach to managing the disease: reducing inflammation to alleviate pain and promoting tissue repair to improve joint function.

What side effects are associated with this type of intervention?

Common treatments for osteoarthritis that target inflammation, such as TNF inhibitors and IL-1 inhibitors like Canakinumab, often have side effects including increased risk of infections, injection site reactions, and potential cardiovascular issues. Platelet-rich plasma (PRP) injections, which are used for cartilage regeneration similar to LNA043, generally have minor and transient side effects such as pain, bleeding, tenderness, swelling, and bruising at the injection site. However, there is also a risk of local infection associated with intraarticular injections.

What prior FDA approvals exist?

There is no specific mention of FDA approvals for Canakinumab or LNA043 in the provided context. However, Canakinumab, a monoclonal antibody targeting IL-1β, is being studied for its anti-inflammatory effects in osteoarthritis. Other IL-1 inhibitors like lutikizumab have shown limited efficacy in knee osteoarthritis. For cartilage regeneration, investigational approaches like lorecivivint have shown some promise in clinical trials, but specific FDA approvals for these treatments are not detailed in the context.

What other types of research exist?

Promising alternatives to Canakinumab and LNA043 for osteoarthritis treatment include: 1) Tocilizumab, an IL-6 receptor blocker, which has shown efficacy in preserving cartilage and increasing bone volume. 2) Cathepsin K inhibitors like L-006235, which reduce cartilage degeneration. 3) GLPG1972/S201086, a selective ADAMTS5 inhibitor, which has demonstrated potential in reducing cartilage breakdown. 4) Intra-articular injections of sprifermin, which have been shown to reduce cartilage loss and promote cartilage gain.

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Anti-inflammatory

Canakinumab + LNA043 for Knee Osteoarthritis

Phase 2

Waitlist Available

Research Sponsored by Novartis Pharmaceuticals

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

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)

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

Must not have

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)

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

Timeline

Screening 3 weeks

Treatment Varies

Follow Up baseline to day 15, 29, 43, 57, 71, 85, 197 and 365

Summary

This trial tests two treatments for knee osteoarthritis. Canakinumab reduces inflammation and pain by blocking a specific protein. LNA043 helps repair damaged cartilage in the knee. The goal is to see if these treatments are safe and effective for patients with knee osteoarthritis.

Who is the study for?

This trial is for adults with moderate to severe knee pain from osteoarthritis, confirmed by specific clinical and imaging criteria. Participants must have had consistent pain over the last 3 months and show inflammation markers in their blood. They can't join if they've had recent knee surgery, plan a knee replacement, suffer from other inflammatory diseases or have significant misalignment in their knees.

What is being tested?

The study tests the safety and effectiveness of two drugs: Canakinumab (anti-inflammatory) and LNA043 (cartilage stimulating), injected into the knee. It will compare these treatments against a placebo to see which is better at reducing osteoarthritis symptoms.

What are the potential side effects?

Potential side effects may include reactions at the injection site, increased risk of infections due to immune system suppression by Canakinumab, and possible unknown risks since LNA043 is newer.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My knee MRI shows I have moderate to severe inflammation.

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My knee arthritis is moderate to severe, with specific joint space measurements.

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I have had moderate to severe knee pain most days in the last 3 months.

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My knee pain score is below 60.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have a condition like rheumatoid arthritis or lupus.

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I have had or plan to have knee surgery, including replacement or other procedures, within the past year.

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My knee is significantly misaligned.

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I have had moderate to severe knee pain most days in the last 3 months.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ baseline to day 15, 29, 43, 57, 71, 85, 197 and 365

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~baseline to day 15, 29, 43, 57, 71, 85, 197 and 365

This trial's timeline: 3 weeks for screening, Varies for treatment, and baseline to day 15, 29, 43, 57, 71, 85, 197 and 365 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Change in Knee injury and Osteoarthritis Outcome Score (KOOS) Pain subscale

Change in cartilage volume in the index region measured by MRI

Secondary study objectives

Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) Function in daily living (ADL) subscale over time

Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain subscale over time

Change in numeric rating scale (NRS) Pain over time

Side effects data

From 2018 Phase 3 trial • 31 Patients • NCT02334748

35%

Nasopharyngitis

29%

Arthralgia

23%

Gastroenteritis

23%

Pyrexia

19%

Abdominal pain

13%

Rhinitis

13%

Tonsillitis

13%

Influenza

13%

Pain in extremity

13%

Conjunctivitis

13%

Paronychia

13%

Pharyngitis

13%

Tracheitis

13%

Viral infection

13%

Headache

13%

Eczema

13%

Diarrhoea

10%

Back pain

10%

Asthenia

10%

Bronchitis

10%

Juvenile idiopathic arthritis

10%

Cough

10%

Lymphadenopathy

Onychomycosis

Neck pain

Tendon pain

Myalgia

Scoliosis

Musculoskeletal pain

Molluscum contagiosum

Labyrinthitis

Oral herpes

Iron deficiency

Sinusitis

Ligament sprain

Limb injury

Arthritis

Pain in jaw

Skin papilloma

Dermatitis allergic

Dry skin

Rash

Abdominal pain upper

Mouth ulceration

Nausea

Toothache

Histiocytosis haematophagic

Epstein-Barr virus infection

Salmonellosis

Intentional overdose

Scar

Bone disorder

Hallucination, auditory

Suicide attempt

Pneumothorax

100%

80%

60%

40%

20%

Study treatment Arm

Canakinumab (ACZ885)

Trial Design

4Treatment groups

Experimental Treatment

Placebo Group

Group I: canakinumab + LNA043Experimental Treatment2 Interventions

canakinumab + LNA043

Group II: canakinumabExperimental Treatment1 Intervention

canakinumab

Group III: LNA043Experimental Treatment2 Interventions

Placebo to canakinumab + LNA043

Group IV: PlaceboPlacebo Group1 Intervention

Placebo to canakinumab

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

canakinumab

2014

Completed Phase 3

~280

LNA043

2015

Completed Phase 2

~190

0 / 8Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for osteoarthritis (OA) often focus on reducing inflammation and promoting cartilage regeneration. Canakinumab, a monoclonal antibody targeting interleukin-1 beta (IL-1β), reduces inflammation by inhibiting this pro-inflammatory cytokine, potentially slowing joint degradation. LNA043 aims to stimulate cartilage regeneration, addressing the cartilage loss that characterizes OA. These mechanisms are important for OA patients as they offer a dual approach to managing the disease: reducing inflammation to alleviate pain and promoting tissue repair to improve joint function.

Bioinformatics analysis combined with experimental validation to explore the mechanism of XianLing GuBao capsule against osteoarthritis.Possible chondroprotective effect of canakinumab: an in vitro study on human osteoarthritic chondrocytes.