Skip to main content
OpenTrials
Completed

NCT Number: NCT04097379

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

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Osteoarthritis (OA) Arthritis Joint Diseases Musculoskeletal Diseases Osteoarthritis Osteoarthritis, Knee Rheumatic Diseases

Age range

35 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Novartis Investigative Site

Leiden, South Holland, 2333 CL, Netherlands

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

LRX712

Drug

LRX712 intra-articular injections

Placebo

Other

Placebo intra-articular injections

Primary outcomes

  1. Change From Baseline in Cartilage Volume in the Index Region Measured by 7 Tesla MRI

    Time frame: Baseline, Week 28

    Magnetic resonance images (MRI) were obtained from the target knee to visualize and quantify changes in the volume of cartilage in the index region. The index region was defined as the combination of the femoral medial anterior (FMA), central (FMC) and posterior (FMP) cartilage subregions in the knee. Change from baseline in cartilage volume was analyzed using the mixed effects model for repeated measures (MMRM). The model included baseline, treatment, timepoint and treatment-timepoints as fixed effects, and participant as random effect. Missing data was assumed to be Missing at Random (MAR).

Secondary outcomes

  1. Time to Reach the Maximum Plasma Concentration (Tmax) of LRX712

    Time frame: Pre-dose, 0.5, 12, 24 and 168 hours after dose on Day 1; Pre-dose, 24 and 168 hours after dose on Day 29; Pre-dose, 24, 168, 1344 and 3360 hours after dose on Day 57

    Tmax is the time to reach maximum (peak) LRX712 concentration after single-dose administration (time). LRX712 plasma concentrations were determined using the actual recorded sampling times and non-compartmental method with Phoenix WinNonlin (Version 8.3). LRX712 was determined by a validated LC-MS/MS method. Concentrations below the lower limit of quantification (LLOQ) were treated as "zero" . LLOQ was 25 pg/mL.

  2. Maximum Observed Plasma Concentration (Cmax) of LRX712

    Time frame: Pre-dose, 0.5, 12, 24 and 168 hours after dose on Day 1; Pre-dose, 24 and 168 hours after dose on Day 29; Pre-dose, 24, 168, 1344 and 3360 hours after dose on Day 57

    Cmax is defined as the maximum (peak) observed concentration following a dose. LRX712 plasma concentrations were determined using the actual recorded sampling times and non-compartmental method with Phoenix WinNonlin (Version 8.3). LRX712 was determined by a validated LC-MS/MS method. Concentrations below the lower limit of quantification (LLOQ) were treated as "zero" . LLOQ was 25 pg/mL.

  3. Minimum Observed Plasma Concentration (Cmin) of LRX712

    Time frame: Pre-dose on Day 29; Pre-dose, 1344 hours after dose on Day 57 (LRX712 15 mg arm) and 3360 hours after dose on Day 57 (LRX712 25 mg and 75 mg arms)

    Cmin is defined as the minimum (peak) observed concentration following a dose. LRX712 plasma concentrations were determined using the actual recorded sampling times and non-compartmental method with Phoenix WinNonlin (Version 8.3). LRX712 was determined by a validated LC-MS/MS method. Concentrations below the lower limit of quantification (LLOQ) were treated as "zero" . LLOQ was 25 pg/mL.

  4. Synovial Fluid Concentrations of LRX712

    Time frame: Pre-dose on Day 1, 29 and 57

    The observed synovial concentration following a dose. LRX712 concentrations were determined using the actual recorded sampling times and non-compartmental method with Phoenix WinNonlin (Version 8.3). LRX712 was determined by a validated LC-MS/MS method. Concentrations below the lower limit of quantification (LLOQ) were treated as "zero" . LLOQ was 20 ng/mL. Samples were collected from a limited number of participants.

  5. Time to Reach the Maximum Plasma Concentration (Tmax) of MAE344

    Time frame: Pre-dose, 0.5, 12, 24 and 168 hours after dose on Day 1; Pre-dose, 24 and 168 hours after dose on Day 29; Pre-dose, 24, 168, 1344 and 3360 hours after dose on Day 57

    Tmax is the time to reach maximum (peak) MAE344 concentration after single-dose administration (time). MAE344 is a metabolite of LRX712 and plasma concentrations were determined using the actual recorded sampling times and non-compartmental method with Phoenix WinNonlin (Version 8.3). MAE344 was determined by a validated LC-MS/MS method. Concentrations below the lower limit of quantification (LLOQ) were treated as "zero" . LLOQ was 100 pg/mL.

  6. Maximum Observed Plasma Concentration (Cmax) of MAE344

    Time frame: Pre-dose, 0.5, 12, 24 and 168 hours after dose on Day 1; Pre-dose, 24 and 168 hours after dose on Day 29; Pre-dose, 24, 168, 1344 and 3360 hours after dose on Day 57

    Cmax is defined as the maximum (peak) observed concentration following a dose. MAE344 is a metabolite of LRX712 and plasma concentrations were determined using the actual recorded sampling times and non-compartmental method with Phoenix WinNonlin (Version 8.3). MAE344 was determined by a validated LC-MS/MS method. Concentrations below the lower limit of quantification (LLOQ) were treated as "zero" . LLOQ was 100 pg/mL.

  7. Minimum Observed Plasma Concentration (Cmin) of MAE344

    Time frame: Pre-dose on Day 29; Pre-dose, 1344 hours after dose on Day 57 (LRX712 15 mg arm) and 3360 hours after dose on Day 57 (LRX712 25 mg and 75 mg arms)

    Cmin is defined as the minimum (peak) observed concentration following a dose. MAE344 is a metabolite of LRX712 and plasma concentrations were determined using the actual recorded sampling times and non-compartmental method with Phoenix WinNonlin (Version 8.3). MAE344 was determined by a validated LC-MS/MS method. Concentrations below the lower limit of quantification (LLOQ) were treated as "zero" . LLOQ was 100 pg/mL.

  8. Synovial Fluid Concentrations of MAE344

    Time frame: Pre-dose on Day 1, 29 and 57

    The observed synovial concentration following a dose. MAE344 is a metabolite of LRX712 and concentrations were determined using the actual recorded sampling times and non-compartmental method with Phoenix WinNonlin (Version 8.3). MAE344 was determined by a validated LC-MS/MS method. Concentrations below the lower limit of quantification (LLOQ) were treated as "zero" . LLOQ was 80 ng/mL. Samples were collected from a limited number of participants.

  9. Change From Baseline in Articular Cartilage [23Na] Content Measured by 7 Tesla MRI

    Time frame: Baseline, Week 16, 28 and 52

    Magnetic resonance images (MRI) were obtained from the target knee to visualize and quantify changes in articular cartilage quality (assessed by changes in glycosaminoglycans content measured by sodium content) in the index region. The index region was defined as the combination of the femoral medial anterior (FMA), central (FMC) and posterior (FMP) cartilage subregions in the knee quality. Change from baseline in articular cartilage content was analyzed using a mixed effects model for repeated measures (MMRM). The model included baseline, treatment, timepoint and treatment-timepoints as fixed effects, and participant as random effect. Missing data was assumed to be Missing at Random (MAR). The data from the three participants who completed dosing with 75 mg LRX712 were considered exploratory.

  10. Change From Baseline in Cartilage Volume in the Index Region Measured by 7 Tesla MRI

    Time frame: Baseline, Week 16 and 52

    Magnetic resonance images (MRI) were obtained from the target knee to visualize and quantify changes in volume of cartilage in the index region. The index region was defined as the combination of the femoral medial anterior (FMA), central (FMC) and posterior (FMP) cartilage subregions in the knee quality. Change from baseline in cartilage volume was analyzed using a mixed effects model for repeated measures (MMRM). The model included baseline, treatment, timepoint and treatment-timepoints as fixed effects, and participant as random effect. Missing data was assumed to be Missing at Random (MAR). The data from the three participants who completed dosing with 75 mg LRX712 were considered exploratory.

Sponsors and collaborators

Lead sponsor

Novartis Pharmaceuticals

Industry

Registry information

Official study title

A Randomized, Placebo-controlled, Subject and Investigator Blinded Study Investigating the Safety, Tolerability and Preliminary Efficacy of 8-week Treatment With Intra-articular LRX712 to Regenerate Articular Cartilage in Patients With Mild/Moderate Knee Osteoarthritis

Important dates

Study start
2020
Primary completion
2024
Study completion
2025
First posted
Sep 20, 2019
Registry last updated
Jan 30, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.