E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
neovascular Age-related Macular Degeneration |
|
E.1.1.1 | Medical condition in easily understood language |
neovascular Age-related Macular Degeneration (nAMD), also commonly referred to as wet AMD |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Eye Diseases [C11] |
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 | 10071129 |
E.1.2 | Term | Neovascular age-related macular degeneration |
E.1.2 | System Organ Class | 10015919 - Eye disorders |
|
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 evaluate the extended durability of brolucizumab in a Treat-to-Control regimen assessed as duration of the last interval with no disease activity up to Week 56 •To evaluate the functional outcomes of brolucizumab in a Treat-to-Control regimen assessed as average change of best corrected visual acuity from baseline at week 52 and week 56 |
|
E.2.2 | Secondary objectives of the trial |
•To evaluate the anatomical outcomes of brolucizumab in all patients and per randomized arm in the core study-assessed by central subfield thickness and number of visits with presence of intra-retinal fluid and/or sub-retinal fluid, and sub-retinal pigment epithelium fluid in the central subfield, as seen by spectral domain ocular coherence tomography at Week 52 and Week 56 •To assess the durability of brolucizumab in all patients and/or per randomized arm in the core study - measured as duration of last interval and maximum interval with no disease activity up to week 56, as well as change of the duration of last interval with no disease activity between baseline and Week 56 •To assess the functional outcomes of brolucizumab per randomized arm in the core study by measuring change of best corrected visual acuity from baseline to Week 52 and Week 56 •To assess the safety of brolucizumab - measured as occurrence of ocular and non-ocular adverse events up to week 56. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Signed informed consent must be obtained prior to participation in the study 2. The participant has successfully completed the TALON core study at the week 64 visit (End of Study) |
|
E.4 | Principal exclusion criteria |
1. Participant has a medical condition or personal circumstance which precludes study participation or compliance with study procedures, as assessed by the Investigator 2. Participant has discontinued study treatment in the core study 3. Anti-VEGF treatment is futile in the study eye, in the investigator's opinion 4. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) pregnancy test 5-Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during the study drug administration and for 3 months after stopping the investigational medication. Highly effective contraception methods include: Total abstinence (when this is in line with the preferred and usual lifestyle of the participant). Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy, or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment. Male sterilization (at least 6 months prior to baseline). For female participants on the study, the vasectomized male partner should be the sole partner for that participant. Use of oral (estrogen and progesterone), injected or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS), or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for example hormone vaginal ring or transdermal hormone contraception. In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking study treatment. Women are considered post-menopausal and not of child-bearingpotential if they have had 12 months of nat ural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy, or tubal ligation at least six weeks before taking study treatment. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child-bearing potential. If local regulations deviate from the contraception methods listed above to prevent pregnancy, local regulations apply and will be described in the informed consent form. 6. Subject requires study treatment every 4 weeks. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
1. Duration of the last interval with no Disease Activity (DA) up to Week 56 2. Change in Best Corrected Visual Acuity (BCVA) extension from baseline at Week 52 and Week 56 |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Up to Week 56 2. At Week 52 and Week 56
|
|
E.5.2 | Secondary end point(s) |
1. Change in Central Subfield Thickness (CSFT) from extension baseline to Week 52 and Week 56. Number of visits with presence of Intraretinal Fluid (IRF) and/or Subretinal Fluid (SRF), and sub-Retinal Pigment Epithelium (sub-RPE) fluid in the central subfield, as assessed by Spectral Domain Ocular Coherence Tomography (SD-OCT) at Week 52 and Week 56 2. Duration of the last interval with no DA up to Week 56. Duration of the maximal intervals with no DA up to Week 56. Change of the duration of last interval with no DA between extension baseline and Week 56. 3. Change in BCVA from extension baseline to Week 52 and Week 56 4. Occurrence of Ocular and Non-ocular Adverse Events (AEs) up to Week 56 |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Up to Week 52 and Week 56. At Week 52 and Week 56. 2. Up to Week 56. 3. Up to Week 52 and Week 56. 4. Up to Week 56. |
|
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 | No |
E.6.7 | Pharmacodynamic | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 32 |
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 |
Australia |
Israel |
Korea, Republic of |
Malaysia |
Taiwan |
United States |
Switzerland |
Belgium |
Czechia |
France |
Germany |
Italy |
Netherlands |
Portugal |
Spain |
Sweden |
|
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
|
|
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 | 4 |
E.8.9.1 | In the Member State concerned days | |
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 | 4 |