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NCT04097379

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

Completed Phase 2 Results posted Last updated 30 January 2026
What this trial tests

Phase 2 trial testing LRX712 in Osteoarthritis (OA) in 45 participants. Completed in 17 January 2025.

Timeline
20 July 2020
Primary endpoint
8 August 2024
17 January 2025

Quick facts

Lead sponsorNovartis Pharmaceuticals
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment45
Start date20 July 2020
Primary completion8 August 2024
Estimated completion17 January 2025
Sites1 location across Netherlands

Drugs / interventions tested

Conditions studied

Sponsor

Novartis Pharmaceuticals — full company profile →

Who can join

Adults 35 to 75, any sex, with Osteoarthritis (OA). Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From Baseline in Cartilage Volume in the Index Region Measured by 7 Tesla MRI Primary · 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).

GroupValue95% CI
LRX712 15 mg63.3± 54.93
LRX712 25 mg49.8± 50.57
Placebo11.6± 45.54
Time to Reach the Maximum Plasma Concentration (Tmax) of LRX712 Secondary · 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.

Day 1
GroupValue95% CI
LRX712 15 mg17.512.0 – 24.0
LRX712 25 mg23.30.50 – 24.1
LRX712 75 mg24.012.0 – 24.1
Day 29
GroupValue95% CI
LRX712 15 mg23.822.6 – 24.0
LRX712 25 mg24.022.2 – 24.2
LRX712 75 mg23.923.8 – 24.0
Day 57
GroupValue95% CI
LRX712 15 mg24.021.9 – 24.0
LRX712 25 mg24.022.0 – 24.1
LRX712 75 mg24.023.5 – 24.0
Maximum Observed Plasma Concentration (Cmax) of LRX712 Secondary · 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.

Day 1
GroupValue95% CI
LRX712 15 mg3.52± 2.07
LRX712 25 mg6.54± 5.33
LRX712 75 mg6.94± 4.96
Day 29
GroupValue95% CI
LRX712 15 mg3.33± 2.57
LRX712 25 mg3.50± 1.43
LRX712 75 mg27.0± 31.6
Day 57
GroupValue95% CI
LRX712 15 mg2.39± 0.951
LRX712 25 mg4.05± 2.25
LRX712 75 mg29.5± 20.4
Minimum Observed Plasma Concentration (Cmin) of LRX712 Secondary · 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.

Dose 1 (pre-dose Day 29)
GroupValue95% CI
LRX712 15 mg0.0735± 0.10
LRX712 25 mg0.0823± 0.115
LRX712 75 mg0.231± 0.401
Dose 2 (pre-dose Day 57)
GroupValue95% CI
LRX712 15 mg0.111± 0.109
LRX712 25 mg0.202± 0.204
LRX712 75 mg0.365± 0.585
Dose 3 (post-dose Day 57)
GroupValue95% CI
LRX712 15 mg0.0439± 0.0740
LRX712 25 mg0.00379± 0.0131
LRX712 75 mg0.0120± 0.0208
Synovial Fluid Concentrations of LRX712 Secondary · 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.

Day 1
GroupValue95% CI
LRX712 15 mg0
LRX712 25 mg0± 0
Day 29
GroupValue95% CI
LRX712 15 mg0
LRX712 25 mg0
Day 57
GroupValue95% CI
LRX712 25 mg0± 0
Time to Reach the Maximum Plasma Concentration (Tmax) of MAE344 Secondary · 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.

Day 1
GroupValue95% CI
LRX712 15 mg23.512.0 – 24.1
LRX712 25 mg24.012.0 – 169
LRX712 75 mg24.124.0 – 24.1
Day 29
GroupValue95% CI
LRX712 15 mg23.822.6 – 24.0
LRX712 25 mg24.022.2 – 193
LRX712 75 mg23.923.8 – 24.0
Day 57
GroupValue95% CI
LRX712 15 mg24.021.9 – 169
LRX712 25 mg24.022.0 – 24.1
LRX712 75 mg24.023.5 – 24.0
Maximum Observed Plasma Concentration (Cmax) of MAE344 Secondary · 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.

Day 1
GroupValue95% CI
LRX712 15 mg38.3± 23.0
LRX712 25 mg52.1± 47.3
LRX712 75 mg75.2± 63.1
Day 29
GroupValue95% CI
LRX712 15 mg42.6± 37.4
LRX712 25 mg40.5± 24.6
LRX712 75 mg281± 329
Day 57
GroupValue95% CI
LRX712 15 mg26.0± 11.8
LRX712 25 mg45.1± 33.7
LRX712 75 mg321± 170
Minimum Observed Plasma Concentration (Cmin) of MAE344 Secondary · 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.

Dose 1 (pre-dose Day 29)
GroupValue95% CI
LRX712 15 mg1.34± 1.76
LRX712 25 mg1.49± 1.82
LRX712 75 mg4.11± 7.01
Dose 2 (pre-dose Day 57)
GroupValue95% CI
LRX712 15 mg2.12± 2.15
LRX712 25 mg3.04± 3.06
LRX712 75 mg5.70± 9.10
Dose 3 (post-dose Day 57)
GroupValue95% CI
LRX712 15 mg0.916± 1.22
LRX712 25 mg0.0557± 0.140
LRX712 75 mg0.257± 0.445
Synovial Fluid Concentrations of MAE344 Secondary · 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.

Day 1
GroupValue95% CI
LRX712 15 mg0
LRX712 25 mg0± 0
Day 29
GroupValue95% CI
LRX712 15 mg0
LRX712 25 mg0
Day 57
GroupValue95% CI
LRX712 25 mg0± 0
Change From Baseline in Articular Cartilage [23Na] Content Measured by 7 Tesla MRI Secondary · 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

Week 16
GroupValue95% CI
LRX712 15 mg-7.4± 12.00
LRX712 25 mg12.7± 11.99
Placebo8.5± 9.20
Week 28
GroupValue95% CI
LRX712 15 mg-15.5± 11.21
LRX712 25 mg8.9± 11.13
Placebo4.0± 9.24
Week 52
GroupValue95% CI
LRX712 15 mg3.1± 12.12
LRX712 25 mg26.6± 11.19
Placebo5.5± 9.20
Change From Baseline in Cartilage Volume in the Index Region Measured by 7 Tesla MRI Secondary · 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)

Week 16
GroupValue95% CI
LRX712 15 mg-48.0± 52.64
LRX712 25 mg-17.4± 50.09
Placebo24.4± 43.05
Week 52
GroupValue95% CI
LRX712 15 mg19.5± 73.11
LRX712 25 mg49.3± 67.29
Placebo123.1± 60.62

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events were reported as "on-treatment" from first dose until last dose of study treatment plus 30 days and as "follow up" from last dose of study treatment plus 29 days up to a maximum duration of approximately 52 weeks.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

LRX712 15 mg
Serious: 0/12 (0%)
Deaths: 0/12
LRX712 25 mg
Serious: 0/14 (0%)
Deaths: 0/14
LRX712 75 mg
Serious: 0/3 (0%)
Deaths: 0/3
LRX712 15mg and 25mg
Serious: 0/26 (0%)
Deaths: 0/26
Placebo
Serious: 0/16 (0%)
Deaths: 0/16
LRX712 15 mg_Post-treatment
Serious: 1/12 (8%)
Deaths: 0/12
LRX712 25 mg_Post-treatment
Serious: 1/14 (7%)
Deaths: 0/14
LRX712 75 mg_Post-treatment
Serious: 0/3 (0%)
Deaths: 0/3
LRX712 15mg and 25mg_Post-treatment
Serious: 2/26 (8%)
Deaths: 0/26
Placebo_Post-treatment
Serious: 1/16 (6%)
Deaths: 0/16
Total
Serious: 3/45 (7%)
Deaths: 0/45

Serious adverse events (3 terms)

ReactionSystemLRX712 15 mgLRX712 25 mgLRX712 75 mgLRX712 15mg and 25mgPlaceboLRX712 15 mg_Post-treatmentLRX712 25 mg_Post-treatmentLRX712 75 mg_Post-treatmentLRX712 15mg and 25mg_Post-…Placebo_Post-treatmentTotal
Myocardial infarctionCardiac disorders
Multiple fracturesInjury, poisoning and procedural complications
Breast cancerNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Other adverse events (64 terms — click to expand)

ReactionSystemLRX712 15 mgLRX712 25 mgLRX712 75 mgLRX712 15mg and 25mgPlaceboLRX712 15 mg_Post-treatmentLRX712 25 mg_Post-treatmentLRX712 75 mg_Post-treatmentLRX712 15mg and 25mg_Post-…Placebo_Post-treatmentTotal
HeadacheNervous system disorders
ArthralgiaMusculoskeletal and connective tissue disorders
Injection site reactionGeneral disorders
Joint stiffnessMusculoskeletal and connective tissue disorders
Limb discomfortMusculoskeletal and connective tissue disorders
NasopharyngitisInfections and infestations
NauseaGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
FatigueGeneral disorders
Back painMusculoskeletal and connective tissue disorders
OsteoarthritisMusculoskeletal and connective tissue disorders
CoughRespiratory, thoracic and mediastinal disorders
VomitingGastrointestinal disorders
MalaiseGeneral disorders
COVID-19Infections and infestations
Gastroenteritis viralInfections and infestations
InfluenzaInfections and infestations
ContusionInjury, poisoning and procedural complications
MyalgiaMusculoskeletal and connective tissue disorders
Pain in extremityMusculoskeletal and connective tissue disorders
SomnolenceNervous system disorders
Oropharyngeal painRespiratory, thoracic and mediastinal disorders
Arrhythmia supraventricularCardiac disorders
PalpitationsCardiac disorders
Ear discomfortEar and labyrinth disorders
Abdominal pain upperGastrointestinal disorders
DysphagiaGastrointestinal disorders
Tooth disorderGastrointestinal disorders
ToothacheGastrointestinal disorders
AstheniaGeneral disorders
Feeling coldGeneral disorders
Influenza like illnessGeneral disorders
Injection site haematomaGeneral disorders
PyrexiaGeneral disorders
Acute sinusitisInfections and infestations
Gastrointestinal infectionInfections and infestations
Oral herpesInfections and infestations
RhinitisInfections and infestations
Upper respiratory tract infectionInfections and infestations
Urinary tract infectionInfections and infestations

Most-reported serious reactions: Myocardial infarction, Multiple fractures, Breast cancer.

Data from ClinicalTrials.gov NCT04097379 adverse events section.

Sponsor's own description

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.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Of mice and men: converging on a common molecular understanding of osteoarthritis.
    Vincent TL. · · 2020 · cited 59× · PMID 32989436 · DOI 10.1016/s2665-9913(20)30279-4
  2. Repurposed and investigational disease-modifying drugs in osteoarthritis (DMOADs).
    Oo WM, Hunter DJ, Hunter DJ. · · 2022 · cited 38× · PMID 35619876 · DOI 10.1177/1759720x221090297
  3. Challenges and opportunities of pharmacological interventions for osteoarthritis: A review of current clinical trials and developments.
    Vrouwe JPM, Burggraaf J, Kloppenburg M, Stuurman FE. · · 2021 · cited 16× · PMID 36474768 · DOI 10.1016/j.ocarto.2021.100212

Verify or expand the search:

Other trials of LRX712

Trials testing the same drug.

Other recruiting trials for Osteoarthritis (OA)

Currently open trials in the same condition.

Other Novartis Pharmaceuticals trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT04097379.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing