What side effects are associated with this type of intervention?

Common treatments for osteoarthritis that target pain reduction and cartilage preservation/regeneration include NSAIDs, COX-2 inhibitors, intraarticular injections, and investigational agents like anti-NGF antibodies and gene therapy. NSAIDs and COX-2 inhibitors can cause gastrointestinal issues, cardiovascular risks, and renal impairment. Intraarticular glucocorticoid injections may lead to joint infection, pain, and cartilage damage with repeated use. Platelet-rich plasma (PRP) injections generally have minor side effects such as pain, swelling, and bruising at the injection site. Anti-NGF antibodies, like tanezumab, have been associated with rapidly progressive OA and increased joint replacement rates. Gene therapy approaches, while promising, are still under investigation, and their long-term safety profiles are not fully established.

What prior FDA approvals exist?

FDA-approved treatments for osteoarthritis primarily focus on pain management rather than cartilage preservation or regeneration. Commonly approved medications include nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen and naproxen, and corticosteroids for intraarticular injections. While investigational treatments such as anti-NGF agents (e.g., tanezumab and fasinumab) and biologics like platelet-rich plasma (PRP) and sprifermin have shown potential in clinical trials, they have not yet received FDA approval for osteoarthritis treatment due to safety concerns and inconsistent efficacy.

What other types of research exist?

Promising novel alternatives to QUC398 for osteoarthritis treatment include: 1) Sprifermin, which has shown to increase cartilage thickness; 2) Platelet-rich plasma (PRP), which reduces inflammation and promotes tissue regeneration; 3) Anti-apoptotic treatments like P188 and caspase-3 inhibitors, which prevent cartilage degradation post-injury; 4) Licofelone, a dual inhibitor of 5-lipoxygenase and cyclooxygenase, which reduces chondrocyte death; 5) Hedgehog signaling inhibitors modulated by kappa opioids, which prevent cartilage degeneration and promote repair; and 6) Tofacitinib and TPCA-1, which exert chondroprotective effects on cartilage extracellular matrix turnover.

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QUC398 for Knee Osteoarthritis

Verified Trial

Phase 2

Recruiting

Research Sponsored by Novartis Pharmaceuticals

Eligibility Criteria Checklist

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

Must have

Weight ≥ 50 kg and body mass index 18 -35 kg/m2 at Screening 1

Kellgren-Lawrence grade 2 to 4 in the tibio-femoral compartment in the target knee confirmed by radiography in standing weight-bearing fixed flexion position and posterior-anterior view, at Screening 1

Must not have

Painful ipsilateral hip OA defined as a Pain NRS ≥3 on the majority of days in the last 3 months prior to Screening 1, as reported by the patient

Symptomatic, patello-femoral pain in the target knee as per investigator's examination at Screening 1

Timeline

Screening 3 weeks

Treatment Varies

Follow Up weeks 1 (day 5), 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52

Summary

This trial is testing a new treatment called QUC398 to see if it can help people with knee osteoarthritis. The study will check if QUC398 can reduce knee pain and protect the cartilage in the knee. Researchers also want to make sure it is safe and well-tolerated.

Who is the study for?

This trial is for adults with knee osteoarthritis (OA) who weigh at least 50 kg, have a BMI of 18-35, and experience moderate to severe knee pain. They must have specific radiographic features in their knees confirming OA severity. Those with severe knee misalignment, patello-femoral pain, inability to undergo MRI scans, or previous use of ADAMTS-5 drugs like QUC398 cannot participate.

What is being tested?

The study tests the effects of an experimental drug called QUC398 on knee pain and cartilage health in people with OA compared to a placebo. Participants will be randomly assigned to receive either the investigational treatment or a placebo to evaluate safety and effectiveness.

What are the potential side effects?

While the side effects are not specified here, common risks may include allergic reactions, gastrointestinal issues, headaches or dizziness. The trial aims to determine if QUC398 is safe and well tolerated by participants.

Eligibility Criteria

Inclusion Criteria

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

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I weigh at least 50 kg and my BMI is between 18 and 35.

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My knee X-ray shows moderate to severe arthritis.

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I have moderate to severe knee pain from arthritis, rated 5-9 on a pain scale.

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I have had moderate to severe knee pain for most of the past week.

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My knee pain score is 60 or less on the KOOS pain scale.

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I weigh at least 50 kg and my BMI is between 18 and 35.

Select...

My knee X-ray shows moderate to severe arthritis.

Select...

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

Select...

I have moderate to severe knee pain from arthritis, rated 5-9 on a pain scale.

Select...

I have had moderate to severe knee pain for most of the past week.

Select...

My knee pain score is 60 or less on the KOOS pain scale.

Exclusion Criteria

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

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I have had hip pain on most days in the last 3 months, rating 3 or more.

Select...

I have knee pain diagnosed by a doctor.

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My knee is severely misaligned by more than 7.5 degrees.

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I have never taken any ADAMTS-5 inhibitors, including QUC398.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ weeks 1 (day 5), 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~weeks 1 (day 5), 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52

This trial's timeline: 3 weeks for screening, Varies for treatment, and weeks 1 (day 5), 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52 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 from baseline in Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain sub-scale at Week 12

Secondary study objectives

Cartilage volume of the knee index region

Pain

Change from baseline in Patient's Global Assessment (PGA) as assessed by NRS

+3 more

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: QUC398Experimental Treatment1 Intervention

QUC398 150 mg/mL, solution for s.c. injection (1 mL). 2 injections will be applied per dose to complete the 300 mg

Group II: PlaceboPlacebo Group1 Intervention

Placebo 0 mg/mL, solution for s.c. injection (1 mL). 2 injections will be applied per dose to ensure blinding

0 / 15Eligibility 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) target pain reduction and cartilage preservation/regeneration through various mechanisms. Nonsteroidal anti-inflammatory drugs (NSAIDs) reduce inflammation and pain by inhibiting cyclooxygenase enzymes, which are involved in the production of inflammatory mediators. Platelet-rich plasma (PRP) injections aim to reduce inflammation and promote tissue repair by delivering high concentrations of growth factors that enhance cellular proliferation and matrix synthesis. Tissue gene therapy, such as TissueGene-C, involves the use of genetically modified cells to overexpress growth factors like TGF-beta1, which support cartilage maintenance and repair. TNF-alpha inhibitors, like infliximab, target inflammatory pathways by blocking the activity of TNF-alpha, a cytokine involved in joint inflammation and degradation. These treatments are crucial for OA patients as they not only alleviate pain but also aim to slow disease progression and improve joint function.

Knee osteoarthritis: pathophysiology and current treatment modalities.