Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase II, Multicenter, Randomized, Single-Masked, Sham-Controlled Study of Safety, Tolerability and Evidence of Activity of Intravitreal APL-2 Therapy in Patients With Geographic Atrophy (GA)
Brief Summary: The primary objectives of the study are to assess the safety, tolerability and evidence of activity of multiple intravitreal (IVT) injections of pegcetacoplan in subjects with Geographic Atrophy associated with Age-Related Macular Degeneration (AMD).


Options:
A: Inclusion Criteria:

* Willingness and ability to provide signed Informed Consent; in addition, at U.S. sites, Health Insurance Portability and Accountability Act (HIPAA) authorization, in other countries, as applicable according to national laws
* Well-demarcated area of GA secondary to age-related macular degeneration (AMD) in the absence of choroidal neovascularization (CNV)

Exclusion Criteria:

* History of vitrectomy surgery, submacular surgery, or other surgical intervention for AMD in the study eye
* Previous subfoveal focal laser photocoagulation in the study eye
* Laser photocoagulation in the study eye
* Prior treatment with Visudyne, external-beam radiation therapy, or transpupillary thermotherapy in the study eye
* GA in either eye due to causes other than AMD
* Diabetic retinopathy in either eye
* Active or history of wet AMD in either eye
* History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use an investigational drug or that might affect interpretation of the results of the study or that renders the patient at high risk for treatment complications
* Active malignancy or history of malignancy within the past 5 years
* Previous participation in any studies of investigational drugs within 3 months preceding Day 0
B: Inclusion Criteria: Unless specified otherwise, ocular specific inclusion criteria apply to the study eye only.

1. Male or Female.
2. Age greater than or equal to 50 years.
3. BCVA of 20/320 (Snellen equivalent) or better using ETDRS charts.
4. Diagnosis of GA of the macula secondary to age-related macular degeneration, confirmed within 14 days prior to randomization by the central reading center (CRC) using Fundus Autofluorescence (FAF) images, as well as the following criteria:

   1. Total GA area must be ≥ 2.5 and ≤ 17.5 mm2 (1 and 7 disk areas \[DA\] respectively), determined by screening images of FAF.
   2. If GA is multifocal, at least one focal lesion must be ≥ 1.25 mm2 (0.5 DA).
   3. GA can be completely visualized on the macula centered image.
   4. GA must be able to be photographed in its entirety.
   5. GA must be able to be measured separately from any areas of peripapillary atrophy as assessed by the CRC.
   6. Presence of any pattern of hyperautofluorescence in the junctional zone of GA. Absence of hyperautoflouorescence (i.e. pattern = none) is exclusionary. See Holz et al. 2007.1
5. Female subjects must be:

   1. Women of non-child-bearing potential (WONCBP), or
   2. Women of child-bearing potential (WOCBP) with a negative pregnancy test at screening and must agree to use protocol defined methods of contraception for the duration of the study.
6. Males with female partners of child-bearing potential must agree to use protocol defined methods of contraception and agree to refrain from donating sperm for the duration of the study.
7. Willing and able to give informed consent.

Exclusion Criteria: Unless specified otherwise, ocular specific inclusion criteria apply to the study eye only.

1. GA due to causes other than AMD such as Stargardt disease, cone rod dystrophy or toxic maculopathies like plaquenil maculopathy.
2. Spherical equivalent of the refractive error demonstrating \> 6 diopters of myopia or an axial length \>26 mm.
3. Any history or current evidence of exudative ("wet") AMD including any evidence of retinal pigment epithelium rips or evidence of neovascularization anywhere in the retina based on fluorescein angiogram as assessed by the CRC.
4. Retinal disease other than AMD; however, benign conditions of the vitreous or peripheral retina are not exclusionary (i.e. pavingstone degeneration).
5. Any ophthalmologic condition that reduces the clarity of the media and that, in the opinion of the Investigator interferes with ophthalmologic examination (e.g. advanced cataract or corneal abnormalities).
6. Any ophthalmologic condition that prevents adequate imaging of the retina judged by the site or CRC.
7. Intraocular surgery (including lens replacement surgery) within 3 months prior to randomization.
8. Aphakia or absence of the posterior capsule. Previous violation of the posterior capsule is also excluded unless it occurred as a result of yttrium aluminum garnet (YAG) laser posterior capsulotomy in association with prior posterior chamber intraocular lens implantation and at least 60 days prior to Day 0.
9. Any ophthalmic condition that may require surgery during the study period.
10. Any contraindication to IVT injection including current ocular or periocular infection.
11. History of uveitis or endophthalmitis.
12. History of IVT injection at any time.
13. Participation in another interventional clinical study, or use of any experimental treatment for AMD or any other investigational new drug within 6 weeks or 5 half-lives of the active (whichever is longer) prior to the start of study treatment. Note: clinical trials solely involving observation, over-the-counter vitamins, supplements, or diets are not exclusionary.
14. Medical or psychiatric conditions that, in the opinion of the investigator, make consistent follow-up over the treatment period unlikely, or in general a poor medical risk because of other systemic diseases or active uncontrolled infections.
15. Any screening laboratory value (hematology, serum chemistry or urinalysis) that in the opinion of the Investigator is clinically significant and not suitable for study participation.
16. Hypersensitivity to fluorescein.
C: Inclusion Criteria:

* At least 18 years of age
* Primary diagnosis of PNH confirmed by high-sensitivity flow cytometry
* On treatment with eculizumab. Dose of eculizumab must have been stable for at least 3 months prior to the Screening Visit
* Hb \<10.5 g/dL at the Screening Visit
* Absolute reticulocyte count \> 1.0x ULN at the Screening Visit
* Platelet count of \>50,000/mm3 at the Screening Visit
* Absolute neutrophil count \>500/mm3 at the Screening Visit
* Vaccination against Neisseria meningitides types A, C, W, Y and B, Streptococcus pneumoniae and Haemophilus influenzae Type B (Hib) either within 2 years prior to Day 1 dosing, or within 14 days after starting treatment with APL-2. Unless documented evidence exists that subjects are non-responders to vaccination as evidenced by titers or display titer levels within acceptable local limits
* Women of child-bearing potential (WOCBP) must have a negative pregnancy test at the Screening and Day -28 Visit (Run-in Period) and must agree to use protocol defined methods of contraception for the duration of the study and 90 days after their last dose of study drug
* Males must agree to use protocol defined methods of contraception and agree to refrain from donating sperm for the duration of the study and 90 days after their last dose of study drug
* Willing and able to give informed consent
* Willing and able to self-administer APL-2 (administration by caregiver will be allowed)
* Have a body mass index (BMI) ≤35.0 kg/m2

Exclusion Criteria:

* Active bacterial infection that has not resolved within 14 week of Day -28 (first dose of APL-2)
* Receiving iron, folic acid, vitamin B12 and EPO, unless the dose is stable, in the 4 weeks prior to Screening
* Hereditary complement deficiency
* History of bone marrow transplantation
* History or presence of hypersensitivity or idiosyncratic reaction to compounds related to the investigational product or SC administration
* Participation in any other investigational drug trial or exposure to other investigational agent within 30 days or 5 half-lives (whichever is longer)
* Currently breast-feeding women
* Inability to cooperate or any condition that, in the opinion of the investigator, could increase the subject's risk of participating in the study or confound the outcome of the study

This study includes cardiac safety evaluations. The following cardiac eligibility criteria are necessary to avoid confounding the cardiac safety outcomes:

* History or family history of Long QT Syndrome or torsade de pointes, unexplained syncope, syncope from an uncorrected cardiac etiology, or family history of sudden death
* Myocardial infarction, CABG, coronary or cerebral artery stenting and /or angioplasty, stroke, cardiac surgery, or hospitalization for congestive heart failure within 3 months or greater than Class 2 Angina Pectoris or NYHA Heart Failure Class \>2
* QTcF \> 470 ms, PR \> 280 ms
* Mobitz II 2nd degree AV Block, 2:1 AV Block, High Grade AV Block, or Complete Heart Block unless the patient has an implanted pacemaker or implantable cardiac defibrillator (ICD) with backup pacing capabilities
* Receiving Class 1 or Class 3 antiarrhythmic agents, or arsenic, methadone, ondansetron or pentamidine at screening
* Receiving any other QTc-prolonging drugs (see Appendix 4 in Section 19.4), at a stable dose for less than 3 weeks prior to dosing
* Receiving prophylactic ciprofloxacin, erythromycin or azithromycin for less than one week prior to the first dose of study medication (must have a repeat screening ECG after one week of prophylactic antibiotics with QTcF \< 470 ms)
D: Inclusion Criteria

1. Participant must understand and sign the protocol's informed consent document (if the participant's vision is impaired to the point where it is not possible to read the informed consent document, the informed consent document will be read in its entirety to the participant).
2. Participant must be able to administer the eye drops or have a caretaker administer the eye drops.
3. Participant must have geographic atrophy (GA) present in both eyes compatible with age-related macular degeneration (AMD). GA is defined as one or more well-defined, usually more or less circular patches of partial or complete depigmentation of the RPE, typically with exposure of underlying choroidal blood vessels. Even if much of the RPE appears to be preserved and large choroidal vessels are not visible, a round-ish patch of RPE partial depigmentation may still be classified as early GA. The GA in each eye must be able to be photographed in their entirety and not contiguous with any areas of peripapillary atrophy, which can complicate area measurements.
4. Participant must have a steady fixation in the study eye in the foveal or parafoveal area and media clear enough for good quality photographs.
5. Female participants of child bearing potential (those who are not post-menopausal or surgically sterile) may participate if they are not lactating and if they agree to adequate birth control methods.

4.5 Exclusion Criteria

1. Participant is \> 60 years of age (to minimize fundus changes from causes other than AMD).
2. Participant is in another investigational study and actively receiving study therapy.
3. Participant is unable to comply with study procedures or follow-up visits.
4. Participant has evidence of ocular disease other than AMD in either eye that may confound the outcome of the study (e.g., diabetic retinopathy, uveitis, etc.).
5. Participant has a chronic requirement (e.g., ≥ four weeks at a time) for ocular medications for diseases, that in the judgment of the examining physician, are vision threatening or may affect the primary outcome (artificial tears are permitted).
6. Participant has evidence of pseudovitelliform macular degeneration that may confound the outcome of the study in either eye.
7. Participant with evidence of vitreo-retinal traction maculopathy that may confound the outcome of the study in either eye.
8. Participant has a history of laser, photodynamic therapy (PDT), intravitreal injection of any agent (e.g., anti-VEGF, triamcinolone, etc.), or any previous treatment for AMD other than AREDS or equivalent supplement formulation in the study eye.
9. Participant has had a vitrectomy, penetrating keratoplasty, trabeculectomy or trabeculoplasty.
10. Participant has undergone lens removal in the last three months.
11. Participant is on chemotherapy.
12. Participant is on ocular or systemic medications known to be toxic to the lens, retina, or optic nerve.
13. Participant with a history of malignancy that would compromise the 2-year study survival.
14. Participant with a history of ocular Herpes simplex virus.
15. Participant with a history of or demonstration of allergy to benzakonium chloride, a preservative agent used in the eye drop.

Answer: B