Safety, tolerability and efficacy of multiple intra-articular injections of LRX712 in patients with knee osteoarthritis.

Phase 1

• Conditions: Cartilage injuries; MedDRA version: 20.0Level: PTClassification code 10031161Term: OsteoarthritisSystem Organ Class: 10028395 - Musculoskeletal and connective tissue disorders; Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

• Registration Number: EUCTR2019-002963-92-NL
• Lead Sponsor: ovartis Pharma AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-10-09
• Last Update Posted: 2 March 2022

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 45

Inclusion Criteria

- Patient must weigh at least 50 kg and have a BMI within 18-35
- 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 joint space width of 1.5 to 3.5 mm (females) or 2 to 4 mm (males) within the medial tibio-femoral compartment of the affected knee
Other protocol-defined inclusion/exclusion criteria may apply.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 40
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5

Exclusion Criteria

- Patient has a known autoimmune disease, inflammatory or chronic arthropathy
- 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) in the index knee = 7.5° 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 ECG reading)
- Signs or Symptoms, in the judgement of the Investigator, of a clinically significant systemic viral, bacterial or fungal infection within 30 days prios to screening

Other protocol-defined inclusion/exclusion criteria may apply.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Primary end point(s): Change from baseline in cartilage volume in the medial femoral condyle at week 28;Timepoint(s) of evaluation of this end point: From baseline visit till Week 28 visit;Main Objective: Efficacy of multiple intra-articular injections of LRX712 in regenerating cartilage as measured with 7T MRI;Secondary Objective: - Efficacy of multiple i.a. injections of LRX712 measured with 7T MRI<br>- The observed time to reach max (Tmax) plasma concentration following drug administration<br>- The observed maximum (Cmax) plasma concentration following drug administration<br>- The observed minimum (Cmin) plasma concentration following drug administration<br>- The observed synovial concentration following drug administration<br>- Safety and Tolerability of multiple injections of LRX712

Secondary Outcome Measures

Name	Time	Method
Timepoint(s) of evaluation of this end point: • Change in articular cartilage [23Na] content from baseline compared<br>to placebo: baseline, week 16, week 28 and week 52<br>• Change from baseline in cartilage volume in the medial femoral<br>condyle: week 16, week 52<br>• PK parameters in plasma: pre-dose to week 28<br>• PK parameter in synovial fluid: day 1 to week 8<br>• Adverse events: Day 1 to week 52;Secondary end point(s): • Change in articular cartilage [23Na] content from baseline compared to placebo<br>• Change from baseline in cartilage volume in the medial femoral condyle <br>• PK parameters in plasma and synovial fluid<br>• Local and systemic adverse events