Safety, Tolerability and Preliminary Efficacy of Multiple Intra-articular Injections of LRX712 in Patients With Knee OA

NCT ID: NCT04097379

Last Updated: 2026-01-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-07-20
• Study Completion Date: 2025-01-17

Brief Summary

This study explored the preliminary efficacy of multiple intra-articular injections of LRX712 by evaluating the ability of the drug to restore structural integrity of articular cartilage. Efficacy was evaluated in the context of the systemic safety and local tolerability of the investigational drug.

Detailed Description

This was an exploratory study, with a 7-week screening period, an 8-week treatment period, and a 44-week follow-up period, using a 3-treatment arm, parallel-group, randomized, double-blind, placebo-controlled clinical study design. The study design implemented for the first six participants enrolled was a 2-treatment arm, parallel -group, randomized, double-blind placebo controlled trial (up until the time when the study was temporarily halted in February 2021) included up to 5 weeks of screening, an 8-week treatment period, and a 44-week follow-up period. The original two-arm study design (75 mg LRX712 vs. placebo) was modified to a three-arm design, with two lower doses of LRX712 (15 mg and 25 mg) vs. placebo, following protocol amendment 4 (16-Jul-2021). Data from the three participants who had completed dosing with 75 mg LRX712 were considered exploratory, and data from the three participants who had completed dosing with placebo were pooled with the data from participants enrolled after the study was restarted with the implementation of protocol amendment 4.

Conditions

Osteoarthritis (OA)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

LRX712 75 mg

LRX712 75 mg was administered i.a. every four weeks, for a total of three administrations.

Group Type: EXPERIMENTAL

LRX712

Intervention Type: DRUG

LRX712 intra-articular injections

Placebo

Placebo was administered i.a. every four weeks, for a total of three administrations.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Placebo intra-articular injections

LRX712 15 mg

LRX712 15 mg was administered intra-articularly (i.a.) every four weeks, for a total of three administrations.

Group Type: EXPERIMENTAL

LRX712

Intervention Type: DRUG

LRX712 intra-articular injections

LRX712 25 mg

LRX712 25 mg was administered i.a. every four weeks, for a total of three administrations.

Group Type: EXPERIMENTAL

LRX712

Intervention Type: DRUG

LRX712 intra-articular injections

Interventions

LRX712

LRX712 intra-articular injections

Intervention Type: DRUG

Placebo

Placebo intra-articular injections

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

Written informed consent must be obtained before any assessment is performed.

To be eligible for inclusion in this study patients must meet all of the following criteria:

• Patient must have a BMI between 18 -35 kg/m2
• Patient must have symptomatic knee osteoarthritis predominantly in one knee (index knee)
• Patient must have knee osteoarthritis (Kellgren-Lawrence grade 2 or 3) in the index knee, as confirmed by radiography
• Patient must have radiographic confirmation of a medial joint space width of 1.5 to 3.5 mm for females, or 2 to 4 mm for males within the medial tibio-femoral compartment of the index knee.

Exclusion Criteria

Subjects meeting any of the following criteria are not eligible for inclusion in this study:

• Patient has a known autoimmune disease, inflammatory or chronic arthropathy other than OA.
• Patient had partial or complete joint replacement in one or both knees.
• Patient has symptomatic, isolated patello-femoral pain in the index knee as per the Investigator's examination.
• Pregnant or nursing (lactating) women.
• Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant.
• Previous use of LRX712 or use of other investigational drugs at the time of enrollment, or within 5 half-lives of enrollment, or within 30 days, whichever is longer; or longer if required by local regulations.
• Patient has malalignment (valgus- or varus-deformity) ≥ 7.5° in the index knee as per anatomic PA axis measured by weight-bearing short knee radiography.
• History of significant cardiac conduction/electrophysiological disorder, e.g. familial long QT syndrome or known family history of Torsades de Pointes or prolonged QT syndrome or QTcF ≥ 450 msec (Fridericia Correction) for males and ≥ 460 msec for females at screening or baseline (by local 12-lead digitized ECG reading).
• Signs or symptoms, in the judgment of the investigator, of a clinically significant systemic viral, bacterial or fungal infection within 30 days prior to screening.

• Minimum Eligible Age: 35 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Novartis Investigative Site

Leiden, South Holland, Netherlands

Countries

Netherlands

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=3122

A Plain Language Trial Summary is available on www.novctrd.com

Other Identifiers

2019-002963-92

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CLRX712A12201

Identifier Type: -

Identifier Source: org_study_id