Clinical Trials Register

Summary
EudraCT Number:	2012-000823-42
Sponsor's Protocol Code Number:	B1181003
National Competent Authority:	Germany - PEI
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2012-08-21
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Germany - PEI

A.2

EudraCT number

2012-000823-42

A.3

Full title of the trial

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

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

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

A.3.2

Name or abbreviated title of the trial where available

B1181003 Clinical Study of RN6G (PF-04382923)

A.4.1

Sponsor's protocol code number

B1181003

A.5.4

Other Identifiers

Name:

US IND Number

Number:

102691

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Pfizer Inc., 235 East 42nd Street, New York, NY 10017
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Pfizer Inc., 235 East 42nd Street, New York, NY 10017
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Pfizer Inc
B.5.2	Functional name of contact point	Clinical Trials.gov Call Center
B.5.3	Address:
B.5.3.1	Street Address	235 E 42nd Street
B.5.3.2	Town/ city	New York
B.5.3.3	Post code	NY 10017
B.5.3.4	Country	United States
B.5.4	Telephone number	+18007181021
B.5.5	Fax number	+13037391119
B.5.6	E-mail	ClinicalTrials.gov_Inquiries@pfizer.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	RN6G
D.3.2	Product code	PF-04382923
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	N/A
D.3.9.2	Current sponsor code	PF-04382923
D.3.9.3	Other descriptive name	RN6G
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for injection/infusion
D.8.4	Route of administration of the placebo	Intravenous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Advanced, Dry, Age-Related Macular Degeneration including Geographic Atrophy

E.1.1.1

Medical condition in easily understood language

A progressive loss of vision in your central visual field (what’s in front of you not to the sides) due to damage of the retina.

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	15.0
E.1.2	Level	PT
E.1.2	Classification code	10064930
E.1.2	Term	Age-related macular degeneration
E.1.2	System Organ Class	10015919 - Eye disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

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

E.2.2

Secondary objectives of the trial

• 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.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Men and women between the ages of 60 and 90 years, inclusive.
2. Diagnosis of a well demarcated area of geographic atrophy (GA) secondary to dry AMD.
One eye (designated as the study eye) must have 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 and has been or is currently being treated with anti
VEGF therapy.

The determination of AREDS AMD Levels 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.

E.4

Principal 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 or stroke 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%). HbA1c must be obtained only for subjects with a known diagnosis of diabetes.

History or diagnosis of ocular disease other than advanced dry AMD or GA in the study eye 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 ocular infection, ocular inflammation or laser or cataract surgery within 3 months of Day 1.

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

History of laser photocoagulation in the study eye.

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 optic amblyopia, glaucoma, optic nerve or other retinal disease or dysfunction (eg, disorders leading to or associated with retinal detachment, macular edema, atrophic retinal holes, retinal tears, retinal detachment, exudative retinal detachment, retinal toxicities due to medications, retinitis pigmentosa). Subjects with cobblestone or paving stone peripheral retinal degeneration are acceptable.

Subjects expected to need ocular surgery during the study.

E.5 End points

E.5.1

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.

E.5.1.1

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)

E.5.2

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 AUCτ, Cmax, Cmin, CL at steady state, and accumulation ratio on AUCτ between the first and last (11th) doses.

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

E.5.2.1

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

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

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

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

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

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

Canada

Germany

Italy

Spain

United Kingdom

United States

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

LSLV

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

248

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

276

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

expected normal treatment of that condition

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2013-02-05

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-01-31

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2013-04-10

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