E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10031161 |
E.1.2 | Term | Osteoarthritis |
E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Efficacy of multiple intra-articular injections of LRX712 in regenerating cartilage as measured with 7T MRI |
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E.2.2 | Secondary objectives of the trial |
- Efficacy of multiple i.a. injections of LRX712 measured with 7T MRI - The observed time to reach max (Tmax) plasma concentration following drug administration - The observed maximum (Cmax) plasma concentration following drug administration - The observed minimum (Cmin) plasma concentration following drug administration - The observed synovial concentration following drug administration - Safety and Tolerability of multiple injections of LRX712 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 index knee Other protocol-defined inclusion/exclusion criteria may apply. |
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E.4 | Principal 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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in cartilage volume in the medial femoral condyle at week 28 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
From baseline visit till Week 28 visit |
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E.5.2 | Secondary end point(s) |
• Change in articular cartilage [23Na] content from baseline compared to placebo • Change from baseline in cartilage volume in the medial femoral condyle • PK parameters in plasma and synovial fluid • Local and systemic adverse events |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
• Change in articular cartilage [23Na] content from baseline compared to placebo: baseline, week 16, week 28 and week 52 • Change from baseline in cartilage volume in the medial femoral condyle: week 16, week 52 • PK parameters in plasma: pre-dose to week 28 • PK parameter in synovial fluid: day 1 to week 8 • Adverse events: Day 1 to week 52 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 4 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 25 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |