Safety, Tolerability and Preliminary Efficacy of Multiple... | NCT04097379

NCT04097379

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module

ID	Type	Description	Link
2019-002963-92	EudraCT Number

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
LRX712 15 mg	Experimental	LRX712 15 mg was administered intra-articularly (i.a.) every four weeks, for a total of three administrations.	Drug: LRX712
LRX712 25 mg	Experimental	LRX712 25 mg was administered i.a. every four weeks, for a total of three administrations.	Drug: LRX712
LRX712 75 mg	Experimental	LRX712 75 mg was administered i.a. every four weeks, for a total of three administrations.	Drug: LRX712
Placebo	Placebo Comparator	Placebo was administered i.a. every four weeks, for a total of three administrations.	Other: Placebo

Name	Type	Description	Arm Group Labels	Other Names
LRX712	Drug	LRX712 intra-articular injections	LRX712 15 mg LRX712 25 mg LRX712 75 mg

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline in Cartilage Volume in the Index Region Measured by 7 Tesla MRI	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).	Baseline, Week 28

Secondary Outcomes

Measure	Description	Time Frame
Time to Reach the Maximum Plasma Concentration (Tmax) of LRX712	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.

Eligibility Module

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.

Other protocol-defined inclusion/exclusion criteria may apply.

Name	Affiliation	Role
Novartis Pharmaceuticals	Novartis Pharmaceuticals	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Novartis Investigative Site		Leiden	South Holland	2333 CL	Netherlands

Label	URL
A Plain Language Trial Summary is available on www.novctrd.com	View source

IPD Sharing Statement Module

Arm/Group Information

ID	Title	Description
FG000	LRX712 15 mg	LRX712 15 mg was administered intra-articularly (i.a.) every four weeks, for a total of three administrations.
FG001	LRX712 25 mg	LRX712 25 mg was administered i.a. every four weeks, for a total of three administrations.
FG002	LRX712 75 mg	LRX712 75 mg was administered i.a. every four weeks, for a total of three administrations.
FG003	Placebo	Placebo was administered i.a. every four weeks, for a total of three administrations.

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	LRX712 15 mg	LRX712 15 mg was administered intra-articularly (i.a.) every four weeks, for a total of three administrations.
BG001	LRX712 25 mg	LRX712 25 mg was administered i.a. every four weeks, for a total of three administrations.

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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

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).

Participants in the safety analysis set from the arms "LRX712 15 mg", "LRX712 25 mg" and "Placebo" who had an available value for the outcome measure as aligned with protocol. The Safety Set comprises all enrolled participants who received any investigational treatment.

Posted

Least Squares Mean

Standard Error

µL

Baseline, Week 28

ID	Title	Description
OG000

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	LRX712 15 mg	LRX712 15 mg was administered intra-articularly (i.a.) every four weeks, for a total of three administrations.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jul 16, 2021	Dec 16, 2025	Prot_000.pdf
SAP	No	Yes	No	Statistical Analysis Plan	Mar 12, 2025	Dec 16, 2025	SAP_001.pdf

ID	Term
D010003	Osteoarthritis
D020370	Osteoarthritis, Knee

ID	Term
D001168	Arthritis
D007592	Joint Diseases
D009140	Musculoskeletal Diseases
D012216	Rheumatic Diseases