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 | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10023476 |
E.1.2 | Term | Knee osteoarthritis |
E.1.2 | System Organ Class | 100000004859 |
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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 in regenerating articular cartilage tissue - To assess the efficacy in relieving OA pain |
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E.2.2 | Secondary objectives of the trial |
- To assess the safety and tolerability - To assess the potential immunogenicity - To assess endogenous ANGPTL3, and PK - To assess the efficacy in regenerating articular cartilage; - To assess the efficacy in maintaining or regenerating articular cartilage - To assess the efficacy on synovitis - To assess the efficacy, in relieving OA pain and improving function over time
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Moderate to severe OA pain (corresponding to NRS Pain ≥5 to ≤9) in the target knee for the majority of days in the last 3 months prior to Screening - KOOS pain subscale <60 for the target knee during Screening - High sensitivity C-reactive Protein (hsCRP) ≥ 1.8 mg/L - Radiographic KL grade 2 to 4 knee OA and joint space width (JSW) 2.0-4.0mm (men) or 1.5-3.5 mm (women) in the medial tibiofemoral compartment (TFC) in the target knee - Contrast-enhanced MRI (CE-MRI) diagnosed moderate or severe knee synovitis based on an established synovititis scoring system (moderate score 9-12 or severe score ≥13) - other protocol-defined inclusion criteria may apply
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E.4 | Principal exclusion criteria |
- History of, or planned; knee replacement(partial or total) in either knee; arthroscopy or lavage in either knee within 6 months prior to screening; any other previous surgical intervention in the target knee, or for the contralateral knee within 12 months prior to Screening, including mosaicplasty, microfracture, meniscectomy >50% or osteotomy - Moderate to severe pain in the contralateral knee for the majority of days in the last 3 months prior to screening - Malalignment >7.5° in the target knee (either varus or valgus) - Any diagnosis of systemic inflammatory arthritis or connective tissue disease including but not limited to rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, gout, Paget's disease, systemic lupus erythematosus) or other systemic condition that might confound assessment of OA (e.g. fibromyalgia) - lpsilateral hip OA or hip prosthesis recently implanted (within 1 year prior to screening) or hip replacement on either side planned within the study period - other protocol-defined exclusion criteria may apply
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E.5 End points |
E.5.1 | Primary end point(s) |
- Change in cartilage volume in the index region measured by MRI - Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain subscale |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
- Baseline to Day 197 - Baseline to Day 85 |
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E.5.2 | Secondary end point(s) |
- Anti-LNA043 antibodies in serum - ANGPTL3 serum concentrations - ANGPTL3 synovial fluid concentrations - LNA043 PK profile in serum (Cmax) - LNA043 PK profile in serum (Tmax) - LNA043 PK profile in serum (AUC) - Change in cartilage volume of the index region measured by MRI - Change in cartilage thickness of the index region measured by MRI - Change in synovitis level measured from Ktrans by Dynamic Contrast Enhanced MRI (DCE-MRI) - Change in numeric rating scale (NRS) Pain over time - Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain subscale over time - Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) Function in daily living (ADL) subscale over time |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- Day 15, 43, 85, 197 and 365 - Day 1, 15, 43, 85, 197 and 365 - Day 1, 15, 43 and 71 - Day 1 and 43 - Day 1 and 43 - Day 1 and 43 - Baseline to Day 197 and 365 - Baseline to Day 197 and 365 - Baseline to Day 85 - Baseline to Day 15, 29, 43, 57, 71, 85, 197 and 365 - Baseline to Day 15, 29, 43, 57, 71, 85, 197 and 365 - Baseline to Day 15, 29, 43, 57, 71, 85, 197 and 365 |
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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 | Yes |
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 | 4 |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 26 |
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 |
Switzerland |
China |
Russian Federation |
United States |
Czechia |
Estonia |
Germany |
Hungary |
Latvia |
Lithuania |
Poland |
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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 | 6 |
E.8.9.1 | In the Member State concerned days | 14 |
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 | 7 |
E.8.9.2 | In all countries concerned by the trial days | 15 |