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 |
• To assess the efficacy of multiple i.a. injections of LNA043 in regenerating the articular cartilage tissue
• To assess safety and local tolerability of multiple i.a. injections of LNA043 |
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E.2.2 | Secondary objectives of the trial |
• To assess the extent of the repair cartilage tissue following multiple i.a. injections of LNA043
• To evaluate systemic and local PK of LNA043 following multiple i.a. injections of LNA043
• To assess the potential immunogenicity of LNA043 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Patient is ≥18 and ≤55 years old at time of screening.
- Patient has a body mass index (BMI) <30 kg/m2 at screening. For patients with a BMI >30 but ≤ 33 kg/m2, eligibility will be decided by consultation with the sponsor.
- Patient has a symptomatic, single, articular cartilage defect of one knee, grade II or IIIA according to the ICRS classification, localized to either the femoral condyles/femoral trochlea or to the patella, based on MRI or arthroscopy performed within 9 months before screening visit and confirmed by screening 3T MRI.
- Patient has an onset of pain and impairment of function between two (2) months and two (2) years before screening.
- Patient reports a KOOS (sports and recreational activities subscale) score of 60 or less at both screening and Day 1. |
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E.4 | Principal exclusion criteria |
- Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 15 days after stopping of investigational drug.
- Regular smokers (consummation of >5 cigarettes/day in the previous 3 months). Urine cotinine levels will be measured during screening for all patients.
- Regular smokers will be defined as any patient who reports tobacco use of > 5 cigarettes/day and/or who has a urine cotinine ≥ 500 ng/mL.
- Patient has radiologically apparent degenerative joint disease in the target knee as determined by Kellgren and Lawrence grade ≥2 based on X-ray evaluation performed within 9 months from screening.
- Patient has had surgical treatment of the target knee using mosaicplasty, microfracture, meniscectomy >50% (Note: prior diagnostic arthroscopy with debridement and lavage, <50% meniscectomy, lateral release, patellar realignment, medial patellofemoral ligament reconstruction are acceptable if performed at least 2 months prior to screening; anterior cruciate ligament reconstrucion is acceptable if performed 12 months prior to screening or less if restoration of joint function is evident and agreed by the sponsor).
- Patient has an unstable target knee joint (including but not limited to posttraumatic or congenital laxity) or insufficiently reconstructed ligaments based on medical history and physical examination by the investigator.
- Patient has patellofemoral dysplasia Dejour Grade B-D based on X-ray or MRI evaluation.
- Patient has malalignment (valgus- or varusdeformity) in the target knee ≥ 5° based on X-ray evaluation. In suspected cases, the mechanical axis must be established radiographically through complete leg imaging during standing and in postero-anterior (PA) projection.
Other protocol defined exclusion criteria's may apply |
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E.5 End points |
E.5.1 | Primary end point(s) |
• Articular cartilage bilayer collagen organization evaluated with T2
relaxation times measured in superficial and deep layers
by T2 mapping MRI at Week 16 and 28
• Number of patients with any adverse events, serious adverse events
and death up to end of study
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• Change in volume of cartilage defect filling evaluated with MRI at Week 16 and 28
• Maximum Observed Plasma Concentration (Cmax) at 0 (pre-dose), 15 min, 60 min and 120 min post-dose Week 1, Week 2, Week 3, Week 4
• Potential immunogenicity of LNA043 presence and characterisation of anti-LNA043 antibodies in serum at Week 1, Week 3, Week 6, Week 16, Week 28
• Area Under the Plasma Concentration-time Curve From 0 to the Last Measurable Concentration (AUClast) at 0 (pre-dose), 15 min, 60 min and 120 min post-dose Week 1, Week 2, Week 3, Week 4 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
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 | 2 |
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 | 10 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Czech Republic |
Denmark |
Germany |
Sweden |
United States |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 14 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 14 |