E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Exudative Age-related Macular Degeneration |
Degenerazione maculare essudativa correlata all`eta' |
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E.1.1.1 | Medical condition in easily understood language |
Wet Age-related Macular Degeneration |
Degenerazione maculare correlata all`eta' |
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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 | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025411 |
E.1.2 | Term | Macular degeneration senile |
E.1.2 | System Organ Class | 10015919 - Eye 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 |
(1) Identify the highest or maximum tolerated dose of AGN-150998 (stage 1) (2) Assess the safety and duration of treatment effect on retinal edema and best corrected visual acuity (stage 1 + stage 2) (3) To characterize the systemic pharmacokinetic profile of AGN-150998. (stage 1+2) |
(1) identificare la dose piu' elevata o massima tollerata di AGN-150998, (2) valutare la sicurezza e la durata degli effetti del trattamento sull`edema retinico, unitamente alla migliore-acuita' visiva corretta (BCVA) e (3) caratterizzare il profilo farmacocinetico sistemico di AGN- 150998. (fase 1+2) |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. active exudative age‐related macular degeneration 2. best‐corrected visual acuity between 20/40 and 20/320 |
1. presenza di una degenerazione maculare essudativa correlata all`eta' 2. BCVA da 20/40 a 20/320 |
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E.4 | Principal exclusion criteria |
1. Females who are pregnant, nursing, or of child‐bearing potential and not on adequate birth control 2. near‐sightedness of 8 diopters or more 3. glaucoma 4. cataract surgery or Lasik within the last 3 months 5. any active ocular infection or inflammation |
1. Pazienti di sesso femminile in gravidanza, allattamento o fertili che non utilizzano metodi di controllo del concepimento 2. miopia superiore a -8 diottrie o piu' 3. glaucoma 4. Chirurgia per la cataratta o Lasik entro gli ultimi 3 mesi 5. Qualsiasi infezione o infiammazione oculare attiva |
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E.5 End points |
E.5.1 | Primary end point(s) |
Efficacy endpoints Stage 1: Central Retina subfield Thickness (CRT) as assessed by spectral domain OCT Stage 2: - Time between the baseline treatment and the need to escape to standard-of-care - CRT as assessed by spectral domain OCT - Best Corrected Visual Acuity (BCVA) Safety Endpoints Stage 1: Reoccurence of retinal edema and need to escape to standard of care treatment (week 4 and beyond): Stage 2: Reoccurence of retinal edema after 2nd injection and need to escape to standard of care treatment (week 4 and beyond): Criteria: - CRT greater than the upper limit of normal (320 µm for Spectralis or 300 µm for Cirrus) - < 10% decrease in CRT from baseline - Loss of > 5 letters in BCVA from any previous visit in conjunction with evidence of an increase in retina fluid - New hemorrhage or increase in existing hemorrhage of greater than 1.25 mm2 (0.5 disc area), associated with either leakage (assessed via FA) or new fluid (assessed via OCT) (eg, intraretinal cysts, cystoid changes or subretinal fluid) or increase in CNV area by fluorescein angiography - Absence of continual improvement in CRT (< 20 μm reduction) on 2 consecutive visits within 7 to 14 days - > 40 micron increase in CRT from the lowest value at any previous visit Pharmacokinetics - PK samples: Determination of serum AGN-150998 concentrations |
Efficacia: Fase 1: CRT misurato tramite OCT Fase 2: - tempo fra il trattamento iniziale e la necessita' di uscita dallo standard di cura - CRT misurato tramite OCT - BVCA Sicurezza: • BCVA • Gravidanza • Segni oculari (cornea, cristallino, iride e reazione dell`umore acqueo [cellulare ed eritematosa]) • Valutazione del cristallino secondo il gruppo di studio Age-Related Eye Disease Study Research (AREDS) (se applicabile) • Anomalie del segmento posteriore • Valutazione di emorragia/distacco retinico • Valutazione della densita' emorragica del vitreo e delle cellule vitreali • Pressione intraoculare • Responsivita' della palpebra/pupilla • Valutazione dell`occhio di studio dopo l`iniezione • Visita fisica (peso corporeo, testa, occhio-orecchio-naso-gola [EENT], collo, cardiovascolare, polmonare, addome, cute/arti, neurologico, linfonodi e muscoloscheletrico) • Segni vitali (polso e pressione sanguigna) • Analisi di laboratorio cliniche (ematologia, biochimica sierica e analisi dell`urina) • Anticorpi anti-AGN-150998 • Eventi avversi - Farmacocinetica: livelli sierici di AGN-150998 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Efficacy and safety endpoints: Day 1, day 3, week 1, week 2, every 4 weeks until week 32 PK endpoints: Day 1 (pre-treatment + 1 hour post-treatment), day 3, week 1, week 2, week 4, (week 6) |
Endoints di efficacia e di sicurezza: Giorno 1, giorno 3, settimana 1, settimana 2, ogni 4 settimane fino alla settimana 32 Endoint di PK: Giorno 1 (pre-trattamento + 1 ora post-trattamento), giorno 3, settimana 1, settimana 2, settimana 4, (settimana 6) |
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E.5.2 | Secondary end point(s) |
Stage 1: n/a Stage 2: - Time between the second treatment and the need to escape to standard-of-care |
Fase1: N/A alla Fase 2: - Tempo trascorso tra il secondo trattamento e la necessita' di uscire dallo standard di cura. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Efficacy: Day 1, day 3, week 1, week 2, every 4 weeks until week 32 |
Efficacia: Giorno 1, giorno 3, settimana 1, settimana 2, ogni 4 settimane fino alla settimana 32 |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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 | Yes |
E.8.1.7.1 | Other trial design description |
Fase2; Fase1 aumento della dose di AGN-150998; 4 cohorti |
Above = design Stage 2; Stage 1: Dose escalation: AGN-150998 only, 4 |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Uno o due dosaggi di AGN-150998 o Lucentis |
One of two dose levels of AGN-150998 or Lucentis |
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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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 12 |
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 |
Switzerland |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
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 | 0 |
E.8.9.1 | In the Member State concerned months | 16 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 16 |
E.8.9.2 | In all countries concerned by the trial days | 0 |