A Proof-of-concept Study to Examine QUC398 in Participants With Knee OA: Osteoarthritis, Knee... (2024)

First Received: July 14, 2022 | Last Updated: June 13, 2024

Phase: Phase 2 | Start Date: November 9, 2022

Overall Status: Active, not recruiting | Estimated Enrollment: 101

Overview

The purpose of the study is to find out if the investigational treatment named QUC398 has beneficial effects on osteoarthritis knee pain and knee cartilage, and if it is safe and well tolerated.

Full Title of Study: “A Randomized, Two-arm, Placebo-controlled, Participant, Investigator and Sponsor-blinded, Proof-of-concept Study Investigating the Efficacy, Safety and Tolerability of QUC398 in Patients With Symptomatic Knee Osteoarthritis”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Triple (Participant, Care Provider, Investigator)
  • Study Primary Completion Date: November 4, 2024

Detailed Description

This is a phase IIa study to establish the effect of QUC398 on pain and cartilage preservation in participants with symptomatic knee OA

Interventions

  • Drug: QUC398
    • QUC398 150 mg/mL, solution for s.c. injection (1 mL)
  • Drug: Placebo
    • Placebo 0 mg/mL, solution for s.c. injection (1 mL)

Arms, Groups and Cohorts

  • Experimental: QUC398
    • QUC398 150 mg/mL, solution for s.c. injection (1 mL). 2 injections will be applied per dose to complete the 300 mg
  • Placebo Comparator: Placebo
    • Placebo 0 mg/mL, solution for s.c. injection (1 mL). 2 injections will be applied per dose to ensure blinding

Clinical Trial Outcome Measures

Primary Measures

  • Change from baseline in Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain sub-scale at Week 12
    • Time Frame: Week 12
    • Efficacy of q4w s.c. injections of QUC398 300 mg vs placebo in relieving OA pain in the target knee

Secondary Measures

  • Cartilage volume of the knee index region
    • Time Frame: Week 52
    • Efficacy of q4w s.c. injections of QUC398 300 mg vs placebo in preservation of cartilage in the medial compartment of the target knee
  • Change from baseline in KOOS Pain subscale
    • Time Frame: Weeks 1 (Day 5), 4, 8, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
    • Efficacy of q4w s.c. injections of QUC398 300 mg vs placebo in relieving OA pain in the target knee over time
  • Change from baseline in pain assessed by a Pain Numerical Rating Scale (NRS)
    • Time Frame: Weeks 1 (Day 5), 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
    • Efficacy of q4w s.c. injections of QUC398 300 mg vs placebo in relieving OA pain in the target knee over time
  • Change in Total KOOS
    • Time Frame: Weeks 1 (Day 5), 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
    • Efficacy of q4w s.c. injections of QUC398 300 mg vs placebo in relieving clinical symptoms and improving function in the target knee over time
  • Change in KOOS subscales: Other symptoms, Function in daily living, Function in sport and recreation, and Knee related quality of life
    • Time Frame: Weeks 1 (Day 5), 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
    • Efficacy of q4w s.c. injections of QUC398 300 mg vs placebo in relieving OA pain in the target knee over time
  • Change from baseline in Patient’s Global Assessment (PGA) as assessed by NRS
    • Time Frame: Weeks 1 (Day 5), 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
    • Efficacy of q4w s.c. injections of QUC398 300 mg vs placebo in relieving OA pain in the target knee over time

Participating in This Clinical Trial

Inclusion Criteria

  • 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 – mJSN 1-2 in the medial tibiofemoral compartment of the target knee, confirmed with Xray by central reader at Screening 1 – Symptomatic OA with moderate to severe pain (corresponding to Pain NRS ≥ 5 to ≤ 9) in the target knee for the majority of days in the last 3 months prior to Screening 1, as per participant's judgement – Symptomatic OA with moderate to severe pain (corresponding to Pain NRS ≥ 5 to ≤ 9) in the target knee at Screening 1 and 2 . Moderate to severe OA pain (corresponding to Pain NRS ≥5 to ≤9) in the target knee during the last 7 days prior to Screening 3, confirmed by: Completed pain diary for at least 6 of the last 7 days prior to Screening 3, AND Diary reported Pain NRS ≥5 to ≤9 for at least 6 of the last 7 days prior to Screening 3 – KOOS pain subscale ≤ 60 in the target knee at Screening 1, Screening 2, and Screening 3 Exclusion Criteria:
  • 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 – Severe malalignment > 7.5º in the target knee (either varus or valgus), measured using standardized knee X-ray at Screening 1 – Patient unable or unwilling to undergo MRI or presenting absolute contraindications to MRI – Previous exposure to any ADAMTS-5 drug, including QUC398. – History or current diagnosis of ECG abnormalities Other protocol-defined inclusion/exclusion criteria may apply

Gender Eligibility: All

Minimum Age: 40 Years

Maximum Age: 80 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Novartis Pharmaceuticals
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Novartis Pharmaceuticals, Study Director, Novartis Pharmaceuticals

Clinical trials entries are delivered from the US National Institutes of Health and are not reviewed separately by this site. Please see the identifier information above for retrieving further details from the government database.

https://trialbulletin.com/lib/entry/ct-05462990

A Proof-of-concept Study to Examine QUC398 in Participants With Knee OA: Osteoarthritis, Knee... (2024)

FAQs

How do people with knee osteoarthritis conceptualize knee confidence a qualitative study? ›

People with knee OA conceptualized confidence with reference to 1 or more of 4 themes: (1) symptoms, (2) functional ability, (3) the internal structure of the knee, and (4) knowledge about knee OA and its management.

What is the mechanism of action of quc398? ›

Mechanism of Action:

QUC-398 exerts its therapeutic effects by targeting A disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS-5), also known as aggrecanase-2. ADAMTS-5 plays a key role in the degradation of cartilage matrix components, contributing to the pathogenesis of OA.

What are the examination findings of osteoarthritis of the knee? ›

Physical examination of the knee should begin with a visual inspection. With the patient standing, look for periarticular erythema and swelling, quadriceps muscle atrophy, and varus or valgus deformities. Observe gait for signs of pain or abnormal motion of the knee joint that can indicate ligamentous instability.

What are the evidence based treatments for osteoarthritis of the knee? ›

This topic last updated: Jun 12, 2024. Evidence-based approaches to the treatment of knee osteoarthritis (OA) include nonpharmacologic, pharmacologic, and surgical modalities targeted at relieving pain, improving joint function, and modifying risk factors for disease progression.

What is the best test for osteoarthritis of the knee? ›

X-rays, which can show loss of joint space, bone damage, bone remodeling, and bone spurs. Early joint damage does not usually appear on x-rays. Magnetic resonance imaging (MRI), which can show damage to soft tissues in and around the joint.

What is the assessment tool for osteoarthritis of the knee? ›

The KOOS evaluates both short-term and long-term consequences of knee injury. It holds 42 items in 5 separately scored subscales; Pain, other Symptoms, Function in daily living (ADL), Function in Sport and Recreation (Sport/Rec), and knee-related Quality of Life (QOL).

What is the mechanism of action of Tripelennamine citrate? ›

Tripelennamine binds to the histamine H1 receptor. This blocks the action of endogenous histamine, which subsequently leads to temporary relief of the negative symptoms brought on by histamine. Well absorbed in the digestive tract.

What is the mechanism of action of mecamylamine? ›

Mecamylamine is a ganglionic blocker which prevents stimulation of postsynaptic receptors by acetylcholine released from presynaptic nerve endings. The hypotensive effect of Mecamylamine is attributed to reduction in sympathetic tone, vasodilation, and reduced cardiac output, and is primarily postural.

What is the mechanism of action of TRPM8? ›

TRPM8 is an ion channel: upon activation, it allows the entry of Na+ and Ca2+ ions into the cell, which leads to depolarization and the generation of an action potential. The signal is conducted from primary afferents (type C- and A-delta) eventually leading to the sensation of cold and cold pain.

What is the gold standard test for osteoarthritis of the knee? ›

The current gold standard for diagnosing OA, besides the always required routine clinical examination of the symptomatic joint, is X-ray imaging (plain radiography), which is safe, cost-efficient and widely available.

What is the new treatment for knee osteoarthritis? ›

A new treatment provides relief for people with osteoarthritis in the knee who are not ready, or not candidates, for knee replacement surgery. Knee embolization, also known as genicular or geniculate artery embolization, is a non-surgical procedure performed by an interventional radiologist.

What does a knee with osteoarthritis look like? ›

You might find you can't move your knee as easily or as far as normal, or it might creak or crunch as you move it. Sometimes your knee might look swollen. This can be caused by two things: Hard swelling: when the bone at the edge of the joint grows outwards, forming bony spurs, called osteophytes (os-tee-o-fites).

What is the best walking aid for osteoarthritis of the knee? ›

Most people with arthritis only need single-point canes. Those with a neurological impairment, significant weaknesses or balance limitations are best suited to quad canes, because they can handle more weight. When being fitted, wear your walking shoes and stand tall with your arms at your sides.

Has anyone ever recovered from osteoarthritis? ›

There's no cure for osteoarthritis, but the condition does not necessarily get any worse over time.

What is the drug of choice for osteoarthritis of the knee? ›

Nonsteroidal anti-inflammatory drugs (NSAIDs).

Over-the-counter nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen (Advil, Motrin IB, others) and naproxen sodium (Aleve), taken at the recommended doses, typically relieve osteoarthritis pain. Stronger NSAIDs are available by prescription.

What are the challenges of osteoarthritis research? ›

The multifaceted nature of osteoarthritis (OA) pain presents a challenge in understanding and managing the condition. The diverse pain experiences, progression rates, individual responses to treatments, and complex disease mechanisms contribute to heterogeneity in the clinical studies outcomes.

What is the holistic approach to osteoarthritis of the knee? ›

Weight Management: Maintaining a healthy weight is essential, as excess weight places added stress on the knee joints. Mind-Body Techniques: Techniques such as mindfulness, yoga, and meditation can alleviate stress, which may exacerbate knee OA symptoms.

What is the epidemiology of osteoarthritis of the knee? ›

The pooled global incidence of knee OA was 203 per 10,000 person-years (95% CI, 106–331) in individuals aged 20 and over. Correspondingly, there are around annual 86⋅7 (95% CI, 45⋅3–141⋅3) million individuals (20 years and older) with incident knee OA in 2020 worldwide.

What are the psychosocial factors of knee osteoarthritis? ›

Depression (47 %, n = 48/102) and education (28 %, n = 29/102) were the most frequently reported psychological and social factors, respectively. Psychological factors were often reported to have an association with/effect on pain (81 %, n = 71/88) and physical function (75 %, n = 56/74).

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