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

NCT04097379 | Completed Phase 2 Results

• 2 other identifiers: CLRX712A122012019-002963-92
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

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.

Conditions

Osteoarthritis (OA)

Keywords

Knee osteoarthritis; Chondroanabolic drug; Magnetic resonance imaging; Patient Reported Outcomes

Outcome Measures

Primary Outcomes (1)

• 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 (10)

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

  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

• Maximum Observed Plasma Concentration (Cmax) of LRX712

  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

• Minimum Observed Plasma Concentration (Cmin) of LRX712

  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)

• Synovial Fluid Concentrations of LRX712

  Pre-dose on Day 1, 29 and 57

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

  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

Study Arms (4)

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

Interventions

LRX712 DRUG

LRX712 intra-articular injections

LRX712 15 mg; LRX712 25 mg; LRX712 75 mg

Placebo OTHER

Placebo intra-articular injections

Placebo

Eligibility Criteria

• Age: 35 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (1)

Novartis Investigative Site

Leiden, South Holland, 2333 CL, Netherlands

Location

Related Links

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

MeSH Terms

Conditions

Osteoarthritis; Osteoarthritis, Knee

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

novartis.email@novartis.com

+ 1 862 778 8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 19, 2019
• First Posted: September 20, 2019
• Study Start: July 20, 2020
• Primary Completion: August 8, 2024
• Study Completion: January 17, 2025
• Last Updated: January 30, 2026
• Results First Posted: January 7, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share

Locations

NL (1)