| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Age-related Macular Degeneration |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 5.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10025409 |
|
| 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 determine the ocular and systemic safety of AG-013958 Suspension for Injection for 13 weeks following administration of a single ST injection and for 104 weeks following multiple administrations by ST injection.
To determine the efficacy of AG-013958 Suspension for Injection in subjects with age-related macular degeneration as assessed by visual acuity at 52 weeks. |
|
| E.2.2 | Secondary objectives of the trial |
To evaluate the visual acuity change with several dose levels and multi-dose schedules over 52 weeks.
To evaluate the change in lesion morphology over 52 weeks as determined by fundus photographs, fluorescein angiography, and optical coherence tomography.
To evaluate systemic exposure and pharmacokinetics of AG-013958 Suspension for Injection after ST injection.
To evaluate the impact of AG-013958 Suspension for Injection treatment on vision-related quality of life. |
|
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
1. Male and/or female subjects nlt 55 years of age. Females must be of non-childbearing potential, ie, surgically sterilized or at least 2 years postmenopausal, and not breast-feeding
2. Subfoveal CNV with minimally classic CNV (classic component <50% of total lesion area) or occult CNV. Subjects with predominantly classic CNV (classic component nlt 50% of total lesion area) will be enrolled starting from stage 2. CNV must comprise at least nlt 50% of the total lesion area. (Lesion characteristics will be independently verified by a central reading center to determine eligibility)
3. For subjects with active occult neovascularization without any classic component:
a. Recent visual decline that in the opinion of the investigator is due to active AMD: subject report of recent visual decline with documentation of nlt 2 lines decline in visual acuity within 12 weeks OR
b. Subretinal blood or lipid deposition must be present, but must comprise <50% of the lesion OR
c. Growth of the lesion by at least 10% increase in its greatest linear dimension within 12 weeks
4. Some portion of the CNV must be under the center of the macula, as verified by the central reading center. If the center is obscured by blood and CNV surrounds the center (270° or more), CNV will be considered to be present under the center
5. No subfoveal fibrosis; total lesion fibrosis or scar must be nmt 25% total lesion area
6. Hemorrhage <50% of total lesion area
7. Total lesion area nmt 9 DA
8. ETDRS best-corrected visual acuity (BCVA) score in the study eye of 73 through 24 letters, inclusive (20/40 through 20/320)
9. Visual acuity score in the fellow eye of nlt 24 letters (20/320 or better)
10. Clear media and dilation to permit good stereo fundus photography
11. WHO performance status of 0, 1 or 2 (Appendix C)
12. Normal ECG or clinically non significant changes. Clinically non significant changes may include evidence of old myocardial infarction (MI), nonspecific ST changes, and old MI with RBBB etc.
13. Subjects who are informed of, and willing and able to comply with, the investigational nature of the study and are able to provide written informed consent in accordance with institutional and regulatory guidelines |
|
| E.4 | Principal exclusion criteria |
1. Serous pigment epithelial detachment without surrounding neovascularization
2. Other serious ocular diseases or conditions, including diabetic retinopathy and glaucoma, that are likely to compromise visual acuity within 1 year
3. Prior subfoveal photocoagulation involving the center of the macula in the study eye; prior juxta-foveal photocoagulation is permitted
4. Prior intravitreal, sub-Tenon, or systemic therapy for AMD, with the exception of nutritional supplements
5. Subjects with prior transpupillary thermotherapy or intravitreal steroids in study eye or those likely to undergo these therapies within 6 months of the start of the study. One prior photodynamic therapy with Visudyne in the study eye is allowed if performed no more than three months before screening.
6. Retinal pigment epithelial tear in the study eye
7. Cataract surgery is indicated in study eye within 12 months
8. Intraocular surgery in study eye within past 3 months; eyelid surgery is permitted if well healed
9. Prior vitrectomy or submacular surgery in the study eye
10. Prior scleral buckling surgery in the study eye
11. Presence of ocular infection in the study eye
12. Presence of severe myopia (–6 diopters or greater) in the study eye
13. Undiagnosed acute illness first observed during screening or stable or severe concurrent medical conditions that, in the investigator's judgment, pose a safety liability, including evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease excluding untreated, asymptomatic, seasonal allergies at time of dosing
14. History of severe cardiac disease (New York Heart Association Class 3 or 4, unstable angina, MI within 6 months, ventricular tachycardia requiring treatment)15. Greater than Stage 1 mild hypertension defined as sitting blood pressure >159/99 mmHg on 2 out of 3 screening evaluations
16. Stroke within past 12 months
17. Physician diagnosed intermittent claudication
18. Prior radiation therapy to head or neck
19. Use of any investigational agent or participation in any other clinical trial in the past 60 days
20. Current use, use within the last 4 weeks, or likely need within 1 year of systemic glucocorticoids. (Dermal glucocorticoids are allowed.)
21. Current use or likely need within 1 year of treatment with anticoagulants (eg, warfarin) unless, in the opinion of the treating physician, the anticoagulants can be stopped at least 4 days before each sub-Tenon injection. (Anticoagulants can be resumed on the day following each sub-Tenon injection if no local hemorrhagic complication is evident.)
22. Allergy to or prior significant adverse reaction to fluorescein
23. Hemoglobin <10 g/dL, WBC <4 x 10 billion/L, platelets <150 x 10 billion/L at Screening
24. Creatinine or BUN >2 x upper limit of normal (ULN) at Screening
25. ALT, AST, and alkaline phosphatase >2 x ULN at Screening
26. Bilirubin >1.5 mg/dL at Screening
27. Proteinuria on urine dipstick greater than 1+ at Screening
28. Blood donation in excess of 500 mL within 60 days prior to the first dose of study medication.
29. History (within 180 days of screening) of alcohol consumption exceeding 7 drinks/week for women or 14 drinks/week for men (1 drink = 150 mL or 5 ounces of wine, 350 mL or 12 ounces of beer; or 44 mL or 1.5 ounces of hard liquor).
30. History of drug abuse within 180 days of Screening |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Safety: Complete ophthalmic exam, tonometry, vital signs, laboratory tests, electrocardiograms (ECGs), adverse events, and efficacy: failure rate (percent of subjects losing nlt 15 letters)
|
|
| 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 | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| 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) | Yes |
| E.7.1.1 | First administration to humans | Yes |
| 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 | No |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Information not present in EudraCT |
| E.8.1.3 | Single blind | Information not present in EudraCT |
| E.8.1.4 | Double blind | Information not present in EudraCT |
| E.8.1.5 | Parallel group | Information not present in EudraCT |
| E.8.1.6 | Cross over | Information not present in EudraCT |
| E.8.1.7 | Other | Information not present in EudraCT |
| 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.8.3 |
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.8.5 | The trial involves multiple Member States | Yes |
| 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 | Information not present in EudraCT |
| 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 |
|
| E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
| 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 | 0 |
| 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 | 0 |
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