Clinical Trials Register

Summary
EudraCT Number:	2017-000946-24
Sponsor's Protocol Code Number:	15-EI-0202
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	GB - no longer in EU/EEA
Date on which this record was first entered in the EudraCT database:	2017-11-24
Trial 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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

UK - MHRA

A.2

EudraCT number

2017-000946-24

A.3

Full title of the trial

Evaluation of Oral Minocycline in the Treatment of Geographic Atrophy Associated with Age-Related Macular Degeneration

A.3.1

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

Oral Minocycline for GA

A.3.2

Name or abbreviated title of the trial where available

Oral Minocycline for GA

A.4.1

Sponsor's protocol code number

15-EI-0202

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT02564978

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	National Eye Institute
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	National Eye Institute
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	The Emmes Corporation
B.5.2	Functional name of contact point	Eric Hardter
B.5.3	Address:
B.5.3.1	Street Address	401 N. Washington Street, Suite 700
B.5.3.2	Town/ city	Rockville, Maryland
B.5.3.3	Post code	20850
B.5.3.4	Country	United States
B.5.4	Telephone number	3012511161
B.5.5	Fax number	3012511355
B.5.6	E-mail	ehardter@emmes.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	Information not present in EudraCT
D.2.1.1.1	Trade name	Minocycline
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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	Minocycline
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Minocycline Hydrochloride
D.3.9.1	CAS number	13614-98-7
D.3.9.4	EV Substance Code	AS1
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	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	No
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Geographic Atrophy Associated with Age-Related Macular Degeneration

E.1.1.1

Medical condition in easily understood language

Geographic Atrophy Associated with Age-Related Macular Degeneration

E.1.1.2

Therapeutic area

Diseases [C] - Eye Diseases [C11]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective of this study is to investigate the safety and possible efficacy of oral minocycline for slowing down the worsening of GA associated with AMD.

E.2.2

Secondary objectives of the trial

Exploratory secondary outcomes will examine the differences in the rates of outcome measure progression in the study eyes between the run-in phase of the study and following IP initiation.

These outcome measures include: GA area expansion based on digital grading of color fundus images by an external Reading Center, changes in BCVA, changes in low luminance VA, changes in central retinal thickness on OCT, and changes in macular sensitivity on microperimetry. Measures obtained from qualifying fellow eyes (i.e., fellow eyes of participants that also meet eye-specific eligibility criteria) will also be analyzed separately and together with study eyes as secondary outcome measures.

Ocular safety outcomes will be indicated by changes in VA, ocular surface changes, intraocular inflammation and any other ocular changes not consistent with the natural progression of GA.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Participant Level:

1. Participant must be 55 years of age or older.
2. Participant (or legal guardian) must understand and sign the protocol’s informed consent document.
3. Participant must have evidence of early or intermediate AMD as defined by characteristic presence of drusen and/or pigmentary changes.
4. Participant must be able to swallow capsules.
5. Participant must have normal renal function and liver function or have mild abnormalities not above grade 1 as defined by the Common Terminology Criteria for Adverse Events v4.0 (CTCAE).
6. Participant must agree to minimize exposure to sunlight or artificial ultraviolet (UV) rays and to wear protective clothing, sunglasses and sunscreen (minimum sun protection factor (SPF) 15) if s/he must be out in the sun.
7. Any female participant of childbearing potential must have a negative pregnancy test at screening and be willing to undergo pregnancy tests throughout the study.
8. Any female participant of childbearing potential and any male participant able to father children must have (or have a partner who has) had a hysterectomy or vasectomy, be completely abstinent* from intercourse or must agree to practice two acceptable methods of contraception throughout the course of the study and for at least one week after investigational product (IP) discontinuation.
Acceptable methods of contraception include:
a. hormonal contraception (i.e., birth control pills, injected hormones, dermal patch or vaginal ring),
b. intrauterine device,
c. barrier methods (diaphragm, condom) with spermicide, or,
d. surgical sterilization (hysterectomy or tubal ligation).
*Abstinence is only acceptable when it is the participant’s preferred and usual lifestyle choice. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.

Study Eye Level:

1. The study eye must have greater than ½ disc area (approximately 1 mm^2) of GA compatible with dry AMD. GA is defined as one or more well-defined and often 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 patch of RPE partial depigmentation may be classified as early GA. The GA in the study eye must be able to be photographed in their entirety, and it must not be contiguous with any areas of peripapillary atrophy, which can complicate area measurements.
2. The total area of GA lesions combined should be less than 7.0 MPS disc areas (DA) (17.78 mm^2) as evident on FAF imaging.
3. The VA of the study eye should be >19 E-ETDRS letters (i.e., 20/400 or better).
4. The study eye must have clarity of ocular media and degree of pupil dilation sufficient to permit adequate fundus photographs.

E.4

Principal exclusion criteria

Participant Level:

1. Participant is actively receiving study therapy in another investigational study.
2. Any female participant of childbearing potential that is pregnant, breast-feeding or planning to become pregnant during the study.
3. Participant is expected to be unable to comply with study procedures or follow-up visits.
4. Participant is on ocular or systemic medications known to be toxic to the lens, retina or optic nerve (e.g., ethambutol, chloroquine, or hydroxychloroquine).
5. Participant has a condition that would preclude participation in the study (e.g., unstable medical status including blood pressure and glycemic control) by interfering with the participant’s ability to engage in the required protocol evaluation and testing and/or comply with study visits.
6. Participant has a history of chronic renal failure requiring dialysis or kidney transplant.
7. Participant has a history of chronic hepatitis or liver failure.
8. Participant has a history of thyroid cancer.
9. Participant has an allergy or hypersensitivity to minocycline or any drug in the tetracycline family.
10. Participant is currently taking minocycline or another tetracycline medication.
11. Participant is taking any medication that could adversely interact with minocycline such as methoxyflurane.
12. Participant has a prior history of idiopathic intracranial hypertension.

Study Eye Level:

1. Current evidence of choroidal neovascularization (CNV) as determined by the treating physician or a history of treatments for CNV.
2. Evidence of retinal atrophy due to causes other than atrophic AMD.
3. Current evidence or history of ocular disorders in the study eye that in the opinion of the investigator confounds study outcome measures, including (but not limited to):
a. non-proliferative diabetic retinopathy involving 10 or more hemorrhages or microaneurysms, or active proliferative diabetic retinopathy
b. Branch or central retinal vein or artery occlusion
c. Macular hole
d. Pathologic myopia
e. Uveitis
f. Pseudovitelliform maculopathy
4. History of vitreoretinal surgery.
5. Need for ocular surgery during the course of the study.
6. Recent history of lens removal (<3 months) or Yttrium Aluminum Garnet (YAG) laser capsulotomy (<1 month).

E.5 End points

E.5.1

Primary end point(s)

The primary outcome is the difference in the rates of GA area expansion in the study eye between the run-in phase of the study and following IP initiation. GA area determination will be based on digital grading of FAF images by an external Reading Center. The primary outcome will be the difference in the rate of GA area expansion from IP start visit (Month 9) to 24 months of treatment (Month 33) compared to initial study visit (Month 0) to IP start visit.

E.5.1.1

Timepoint(s) of evaluation of this end point

The study will require a minimum of 11 visits (Months 0, 3, 6, 9, 12, 15, 21, 27, 33, 39, and 45). Comprehensive ophthalmologic examinations will be performed during these visits.

E.5.2

Secondary end point(s)

Exploratory secondary outcomes will examine the differences in the rates of outcome measure progression in the study eyes between the run-in phase of the study and following IP initiation. These outcome measures include: GA area expansion based on digital grading of color fundus images by an external Reading Center, changes in BCVA, changes in low luminance VA, changes in central retinal thickness on OCT, and changes in macular sensitivity on microperimetry. Measures obtained from qualifying fellow eyes (i.e., fellow eyes of participants that also meet eye-specific eligibility criteria) will also be analyzed separately and together with study eyes as secondary outcome measures.

Ocular safety outcomes will be indicated by changes in VA, ocular surface changes, intraocular inflammation and any other ocular changes not consistent with the natural progression of GA.

E.5.2.1

Timepoint(s) of evaluation of this end point

The study will require a minimum of 11 visits (Months 0, 3, 6, 9, 12, 15, 21, 27, 33, 39, and 45). Comprehensive ophthalmologic examinations will be performed during these visits. Comprehensive safety evaluations will be performed at Months 0, 9, 15, 21, 27, 33, 39, and 45.

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

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

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

E.8.1.1

Randomised

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

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

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

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

United Kingdom

United States

E.8.7

Trial has a data monitoring committee

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

The study is designed with a common termination date, meaning it will not terminate until the last recruited participant has completed the Month 45 visit.

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