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

Novartis

Status and phase: Completed; Phase 2

Conditions: Osteoarthritis (OA)

Treatments: Drug: LRX712; Other: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT04097379

2019-002963-92 (EudraCT Number)

CLRX712A12201

Details and patient eligibility

About

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.

Full 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.

Enrollment: 45 patients

Sex: All

Ages: 35 to 75 years old

Volunteers: No Healthy Volunteers

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.

Other protocol-defined inclusion/exclusion criteria may apply.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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45 participants in 4 patient groups, including a placebo group

LRX712 15 mg

Experimental group

Description:

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

Treatment:

Drug: LRX712

LRX712 25 mg

Experimental group

Description:

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

Treatment:

Drug: LRX712

LRX712 75 mg

Experimental group

Description:

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

Treatment:

Drug: LRX712

Placebo

Placebo Comparator group

Description:

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

Treatment:

Other: Placebo