A trial to investigate the efficacy and safety of treatment with RN6G in patients with age related macular degeneration resulting in age-related loss of central vision.

• Register: EUCTR
• Last refreshed on: 13 May 2013
• Main ID: EUCTR2012-000823-42-GB
• Date of registration: 23/08/2012
• Prospective Registration: Yes
• Primary sponsor: Pfizer Inc., 235 East 42nd Street, New York, NY 10017
• Public title: A trial to investigate the efficacy and safety of treatment with RN6G in patients with age related macular degeneration resulting in age-related loss of central vision.
• Scientific title: A PHASE 2 MULTI-CENTER, RANDOMIZED, DOUBLE-MASKED, PLACEBO CONTROLLED, MULTI-DOSE STUDY TO INVESTIGATE THE EFFICACY, SAFETY, PHARMACOKINETICS AND PHARMACODYNAMICS OF RN6G (PF 04382923) IN SUBJECTS WITH GEOGRAPHIC ATROPHY SECONDARY TO AGE-RELATED MACULAR DEGENERATION - B1181003 Clinical Study of RN6G (PF-04382923)
• Date of first enrolment: 16/11/2012
• Target sample size: 276
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-000823-42
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 4

Countries of recruitment

Canada, Germany, Italy, United Kingdom, United States

Contacts

• Name: Clinical Trials.gov Call Center
• Affiliation: Pfizer Inc

• Name: Clinical Trials.gov Call Center
• Affiliation: Pfizer Inc

Key inclusion & exclusion criteria

Inclusion criteria:
1. Men and women of non-child bearing potential between the ages of 60 and 90 years, inclusive at Day 1.
2. Diagnosis of a well demarcated area of geographic atrophy (GA) secondary to dry AMD.
One eye (designated as the study eye) must have GA that is seen on fundus photographs or opthalmoscopy defined as one or more areas of partial or complete depigmentation of the RPE, usually having a round or oval shape, sharp margins, and visibility of underlying large choroidal vessels. On optical coherence tomography, in areas of GA, there is attenuated or absent RPE and loss of overlying outer retinal layers.

This definition clarifies the following for AREDS AMD Levels Defined for Eyes):
• 3d: Geographic atrophy within grid but none at the center of the macula.
• 4a: Geographic atrophy in central subfield with at least questionable involvement of center of macula.

The other eye (designated as the fellow eye) can have Level 3 or 4a AMD. If both eyes have Level 3d or 4a AMD, then
the eye with the best BCVA would be considered the study eye; otherwise it should be considered the fellow eye. If
the ETDRS BCVA is the same in each eye, then the Investigator will designate the study and fellow eye.

A subject will be excluded from study if the fellow eye has Level 4b (evidence of neovascular AMD) and has been or is currently being treated with anti VEGF therapy.


The determination of the eligibility of subjects based on the GA criterion will be made by a Central Reader.
3. GA total area between 2.0 and 17.5 mm2.
4. Best corrected visual acuity (BCVA) of =54 letter (20/80 (Snellen VA equivalent) or better in the study eye as
determined using an ETDRS chart.
5. Evidence of a personally signed and dated informed consent document indicating that the subject (or a legal
representative) has been informed of all pertinent aspects of the study.
6. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study
procedures.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 28
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 248

Exclusion criteria:
Any disease or condition that might compromise the cardiovascular, hematological, renal, hepatic, pulmonary, endocrine, central nervous, immune, or gastrointestinal systems (unless deemed not clinically significant by the Investigator and Sponsor) such as, but not limited to:
a. Diagnosis or history of Alzheimer’s disease, dementia of any cause such as untreated thyroid disease, stroke, transient ischemic attacks (TIAs) or neuro degenerative disorders (eg, Parkinson’s disease, Lewy body disease, fronto temporal dementia, vascular dementia);
b. History or systemic signs of inflammatory bowel disease, multiple sclerosis, systemic lupus erythematosus;
c. History of cancer within the last 5 years (except for cutaneous basal cell or squamous cell cancer resolved by excision);
d. Presence of uncontrolled hypertension (uncontrolled hypertension is defined as a systolic blood pressure greater than 140 mm Hg or a diastolic blood pressure greater than 90 mm Hg, even with treatment). Subjects who have hypertension and are controlled on stable dosages of anti hypertensive medications can be included;
e. Poorly controlled Type 1 and Type 2 diabetes mellitus (HbA1c >9%).
Exclusions Related to Ocular Conditions (in the study eye unless otherwise indicated)
1. History or diagnosis of ocular disease other than advanced dry AMD or GA that would confound the results of the study, such as diabetic retinopathy with microhemorrhage, uveitis (CTCAE Grade =2), or pseudovitelliform macular degeneration.

History or diagnosis of exudative (wet) AMD, with subretinal or choroidal neovascular lesions in the study or fellow eye.

History of or active intraocular and globe infection including infection of the cornea, sclera or episclera and presence of extra-ocular infection that requires long term treatment.

Active intra- or extra-ocular inflammation at the screening visit that requires chronic (ie, greater than 2 weeks) treatment with corticosteroids.

Laser or cataract surgery within 3 months of Day 1 or subjects expected to need ocular surgery during the study.

History of ocular trauma or surgery (other than laser or cataract surgery) within 6 months of Day 1.

History of laser photocoagulation unless the site is anterior to the equator.

Presence of ocular lens opacities preventing vision testing: cortical opacity greater than standard 3, posterior subcapsular opacity greater than standard 2, or a nuclear opacity greater than standard 3 (as measured on the AREDS clinical lens grading system).

History of the following within 6 months or active disease within 6
months of Day 1 of the following:
- optic nerve disease, either primary or secondary (eg, due to medications); retinal disease disorders leading to or associated with retinal detachment:
- Epiretinal membrane is acceptable if stable for more than 6 months with no retinal detachment or edema;
- Vitreous detachment is acceptable if there's no pulling of the
posterior retina;
- macular edema;
- retinitis pigmentosa in study or fellow eye;
- atrophic retinal holes if they are posterior to the equator;
- lattice degeneration;
- uncontrolled glaucoma i.e. fluctuating IOP, IOP > 22mmHg or if there
is worsening of the visual field within 6 months of screening;
- retinal toxicities due to medications (even if observed in the fellow
eye).




Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Advanced, Dry, Age-Related Macular Degeneration including Geographic Atrophy
MedDRA version: 15.1 Level: PT Classification code 10064930 Term: Age-related macular degeneration System Organ Class: 10015919 - Eye disorders

Therapeutic area: Diseases [C] - Eye Diseases [C11]

Intervention(s)

Product Name: RN6G
Product Code: PF-04382923
Pharmaceutical Form: Solution for injection
Current Sponsor code: PF-04382923
Other descriptive name: RN6G
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Solution for injection/infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Main Objective: To determine the efficacy of RN6G in subjects with geographic atrophy in the study eye.

Primary end point(s): The mean reduction in the rate of growth of GA area (in mm2) at 30 days post last dose administration (Day 309) and at end of study with FAF.

Timepoint(s) of evaluation of this end point: The mean reduction in the rate of growth of GA area (in mm2) at 30 days post last dose administration (Day337)

Secondary Objective: • To examine retinal structural and functional deficits with ocular assessments for the study and the fellow eye.
• To examine the safety, tolerability and immunogenicity of RN6G in subjects.
• To characterize the population pharmacokinetic (PK) profile of RN6G.
• To demonstrate the effect of RN6G on plasma Aß(1-x)(total), Aß(1-40) and Aß(1-42) concentrations.

Secondary Outcome(s)

Secondary end point(s): BCVA
• The mean BCVA letter number and line number after RN6G at 9, 12, 15 months and end of study compared to baseline and placebo.
• The mean percentage change from baseline in the correct number of letters after RN6G at 9, 12, 15 months and end of study.
• The mean percentage change from baseline in the correct number of lines after RN6G at 9, 12, 15 months and end of study.

Low Luminance (LL) BCVA
• The mean LL BCVA letter number and line number after RN6G at 9, 12, 15 months and end of study compared to baseline and placebo.
• The mean percentage change from baseline in the correct number of letters after RN6G at 9, 12, 15 months and end of study.
• The mean percentage change from baseline in the correct number of lines after RN6G at 9, 12, 15 months and end of study.

Contrast Sensitivity
• The mean change in Logmar units compared to baseline and placebo at 9, 12, 15 months and end of study.
• The percentage change from baseline in Logmar units at 9, 12, 15 months and end of study.

Reading
• The mean reading acuity and speed change from baseline at 9, 12, 15 months and end of study.
• The mean reading acuity and speed change from placebo at 9, 12, 15 months and end of study.
• The mean critical print size change from baseline and placebo at 9, 12, 15 months and end of study.
• The percentage change from baseline in reading acuity and speed at 9, 12, 15 months and end of study.

Safety
• Incidence, severity and causal relationship of treatment emergent AEs (TEAEs).
• Incidence of abnormal and clinically relevant safety laboratories including clinical chemistry, hematology and coagulation assessments.
• Abnormal and clinically relevant changes in vital signs, BP, and ECG parameters.
• Incidence of anti-drug-antibodies.

Pharmacokinetics
• Plasma RN6G concentrations at specified time points and population PK parameter estimates for AUCt, Cmax, Cmin, CL at steady state, and accumulation ratio on AUCt between the first and last (11th) doses.

Pharmacodynamics
• Change from baseline (absolute and %) of plasma Aß(1-x) (total), Aß(1-40) and Aß(1-42) concentrations.

Timepoint(s) of evaluation of this end point: 1) The mean BCVA letter number and line number after RN6G at 9, 12, and 15 months compared to placebo.
2) The mean percentage change from baseline in the correct number of letters after RN6G at 9, 12 and 15 months.
3) The mean percentage change from baseline in the correct number of lines after RN6G at 9, 12, and 15 months

Secondary ID(s)

B1181003

2012-000823-42-DE

102691

Source(s) of Monetary Support

Pfizer Inc., 235 East 42nd Street, New York, NY 10017