Long–term Analysis of DImethyl fumarate, to slow the Growth of Areas of Geographic Atrophy

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Eye Diseases [C11]

Trial duration

27 Jun 2024 → ongoing

Decision date (initial)

2024-06-27

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-510741-33-00

EudraCT number

2019-003413-33

ClinicalTrials.gov

NCT04292080

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy

Compare the efficacy at month 12, on the rate of change in Geographic Atrophy area, of twice-daily oral Dimethyl Fumarate (120mg x2 the 1st week, 240mg x2 for 51 weeks thereafter), versus standard of care, in patients with Geographic Atrophy resulting from the dry form of AMD

Conditions and MedDRA coding

Macular degeneration

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Age 55 years of age to 85 years old at the moment of inclusion
2. Participant must understand and sign the protocol's informed consent document
3. Participant must have central or non-central geographic atrophy (GA) in at least one eye. GA should be at least 0.75 disk areas (DA) in size but no more than 8 disk areas (DA); approximately 2.54 mm2 is 1 DA
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. Participant must have visual acuity between 20/20 and 20/200 in the affected eye
6. No suggestive sign of progressive multifocal leukoencephalopathy on brain MR Imaging within 3 months of Dimethyl Fumaratetreatment Initiation (Only the patients randomized in the Dimethyl FumarateGroup will have to go through the MR Imaging)
7. Male participants with female partners capable of conceiving children will be required to use contraception (condom) during the study and for four months after their last experimental treatment caps
8. No documented history of heart disease, absence of family history of sudden death, and QTc duration within normal value (<480ms)
9. Participants must be affiliated to a social security scheme

Exclusion criteria 31

1. Participant is in another interventional investigational study < 3 months before inclusion
2. Participant is unable to comply with study procedures or follow-up visits
3. Participant has evidence of ocular disease other than GA in either eye that may confound the outcome of the study (e.g., glaucoma, diabetic retinopathy with 10 or more hemorrhages or micro-aneurysms, uveitis, pseudo-vitelliform macular degeneration, exudative macular degeneration, moderate/severe myopia)
4. Participant with antecedent of neo-vascular AMD
5. Participant has received treatment for exudative AMD, such as macular laser, photodynamic therapy (PDT) or anti-vascular endothelial growthfactor (anti-VEGF) therapy intra-vitreal (IVT) injection or of any agent (e.g., triamcinolone) in the study eye within the last four months prior to study enrollment. Vitamin supplementation for AMD is not considered an exclusionary criterion
6. Participant has had a vitrectomy on the study eye
7. Participant is expected to need ocular surgery during the course of the trial
8. Participant has undergone lens removal in the last three months or Yttrium Aluminium Garnet (YAG) laser capsulotomy within the last month
9. Participant is on chemotherapy
10. Participant is on chronic (more than 3 months) immunosuppressive medication administered via ocular or systemic route(s) or is immunosuppressed
11. Participant is on ocular or systemic medications known to be toxic to the lens, retina or optic nerve
12. Participant with a history of malignancy that would compromise the 2-year study survival
13. Participant with a history of ocular herpes simplex virus (HSV)
14. Contra-indications or known hyper-sensibility to Dimethyl Fumarate or experimental treatment excipients
15. Severe active gastrointestinal disease
16. Contra-indications to an MRI using gadolinium such as pace maker, cardiac valve non IRM compatible, cochlear implant or any metallic implant non IRM compatible
17. Any contraindications to gadolinium including pregnancy, previous allergic reaction, severe kidney disease
18. Any contraindications to aspirin
19. Any screening laboratory value (hematology, serum chemistry or urinalysis) 3 times above normal values or that in the opinion of the Investigator is clinically significant and not suitable for study participation
20. Lymphopenia: below normal laboratory values at inclusion
21. Severe impairment of a vital organ including severe liver and renal impairment
22. Previous organ allograft
23. Patients taking the following non-authorized treatment 3 months prior enrolment: other fumaric acid derivatives (topical (ocular) or systemic), immuno-modulators via ocular or systemic routes (including interferons, sirolimus, chronic use of glucocorticoids), cytotoxic treatments and live attenuated vaccines.(NB: During the experimental treatment period and 3 months thereafter the concomitant use of non-authorized treatment cited above is not allowed in patients randomized in the Dimethyl Fumarate group)
24. Patients taking the following non-authorized treatment 3 months prior enrolment: nephrotoxic treatment (aminoglycosides, diuretics, nonsteroidal anti-inflammatory drugs (via ocular or systemic routes) or lithium). (NB: During the experimental treatment period and 3 months thereafter the concomitant use of non-authorized nephrotoxic treatment cited above is not allowed in patients randomized in the Dimethyl Fumarate group)
25. Any condition that, in the opinion of the investigator, would preclude participation in the study (e.g., unstable medical status including blood pressure and glycemic control)
26. History of cancer (other than a non-melanoma skin cancer) diagnosed within the past five years that could be worsened by immunosuppression(In case of history of cancer the risk of immunosuppression must be determined by a specific oncology consultation prior to enrollment.)
27. Ocular or peri-ocular inflammation or infection in either eye
28. Presence of active or inactive toxoplasmosis in any or both eye(s)
29. Presence of active or latent tuberculosis infection
30. Female participants of childbearing potential (those who are not post-menopausal or surgically sterile). Postmenopausal state is 12 months of amenorrhea + high level of FSH if required
31. Persons under curatorship or guardianship

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Rate of Change in Area of Geographic Atrophy (GA), based on masked, digital grading as measured on Fundus Auto-fluorescence ((FAF) Imaging Using a Confocal Scanning Ophthalmoscope by an External Reading Center at 12, Months compared to value at Baseline Day 1

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris Cedex 10

Postcode

75475

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Project Manager

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Project Manager

Locations

1 EU/EEA country · 11 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 7 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications