Efficacy of Dimethyl Fumarate in Reducing Geographic Atrophy Progression in Patients with Dry Age-Related Macular Degeneration: A 12-Month Comparative Study
- Trial ID
- 2024-510741-33-00
- Protocol
- P170919
Trial statistics
Diseases & Conditions
Objectives
The primary objective of the study is to compare the **efficacy** of twice-daily oral **Dimethyl Fumarate** with the standard of care in patients with **Geographic Atrophy** resulting from the dry form of **Age-related Macular Degeneration (AMD)**. The focus is on evaluating the rate of change in the Geographic Atrophy area over a 12-month period. This is clinically relevant as it aims to determine whether Dimethyl Fumarate can effectively slow the progression of Geographic Atrophy, a significant cause of vision loss in AMD patients.
Participants
The clinical trial focuses on patients with **macular degeneration**, specifically the dry form of age-related macular degeneration (AMD) leading to Geographic Atrophy. The study population includes both male and female participants aged between 55 and 85 years. Participants are required to have a general health status free from heart disease and a family history of sudden death, with a QTc duration within normal values. The trial does not involve a vulnerable population. Participants must have central or non-central geographic atrophy in at least one eye, with specific size criteria, and maintain a steady fixation in the study eye. Visual acuity must range between 20/20 and 20/200 in the affected eye. Lifestyle considerations include the requirement for male participants with female partners capable of conceiving to use contraception during the study and for four months after the last treatment. The sponsor has not provided information regarding the total number of participants in the trial.
Plans and Procedures
The clinical trial is designed to evaluate the efficacy of **dimethyl fumarate** in slowing the progression of geographic atrophy associated with age-related **macular degeneration**. This is a Phase 4, randomized, double-blind, controlled trial comparing the effects of twice-daily oral administration of dimethyl fumarate against the standard of care. The trial will span approximately 51 weeks, with an estimated completion date in October 2027. Participants will be randomly assigned to receive either 120 mg of dimethyl fumarate twice daily for the first week, followed by 240 mg twice daily for the remaining 51 weeks, or a standard treatment regimen.
The study will include several key visits: an initial screening visit, regular follow-up visits, and an end-of-study visit. During the **screening visit**, eligibility will be assessed based on criteria such as age (55-85 years), the presence of geographic atrophy in at least one eye, and visual acuity requirements. Participants must also provide informed consent and meet other health-related criteria. Follow-up visits will occur at regular intervals to monitor the rate of change in the area of geographic atrophy, using masked digital grading on fundus auto-fluorescence imaging. The **end-of-study visit** will evaluate the primary endpoint, which is the rate of change in the area of geographic atrophy at 12 months compared to baseline.
Participant involvement is expected to last for the entire duration of the trial, approximately 51 weeks. However, conditions such as non-compliance with the study protocol, adverse events, or withdrawal of consent may lead to early termination from the study. The trial aims to provide valuable insights into the long-term effects of dimethyl fumarate on geographic atrophy progression, contributing to the understanding and management of macular degeneration.
Treatment
The clinical trial involves the administration of **Dimethyl Fumarate**, a chemical compound used as the experimental medication. The pharmaceutical form of this medication is a **gastro-resistant capsule, hard**, designed to withstand the acidic environment of the stomach and dissolve in the intestines. The active substance, **Dimethyl Fumarate**, is administered orally. The dosing regimen for the trial consists of an initial dosage of 120 mg taken twice daily during the first week, followed by an increased dosage of 240 mg taken twice daily for the subsequent 51 weeks. The maximum daily dose is 240 mg, with a total maximum dose of 85,680 mg over the treatment period. The trial aims to evaluate the efficacy of this regimen in slowing the progression of **Geographic Atrophy** associated with the dry form of **Age-related Macular Degeneration (AMD)**.
In addition to the experimental treatment, the study includes a comparator group receiving standard-of-care therapy. This group serves as a control to assess the relative efficacy of **Dimethyl Fumarate**. The standard-of-care therapy is not specified in the provided data, but it typically involves treatments that are currently accepted and widely used in clinical practice for managing **Geographic Atrophy**. The trial does not utilize a placebo, focusing instead on direct comparison with existing therapeutic approaches.
Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the prescribed regimen. This monitoring is crucial for maintaining the integrity of the study results and ensuring that any observed effects can be accurately attributed to the experimental treatment. The trial's main objective is to compare the rate of change in the area of **Geographic Atrophy** at month 12 between the **Dimethyl Fumarate** group and the standard-of-care group.
Efficacy
The efficacy of the clinical trial will be assessed by evaluating the **Rate of Change in Area of Geographic Atrophy (GA)**. This primary endpoint will be measured using masked, digital grading on Fundus Auto-fluorescence (FAF) Imaging. The imaging will be conducted with a Confocal Scanning Ophthalmoscope and analyzed by an External Reading Center. The assessment will occur at 12 months and will be compared to the baseline value recorded on Day 1. The trial aims to compare the efficacy of twice-daily oral **Dimethyl Fumarate** against the standard of care in patients with Geographic Atrophy resulting from the dry form of Age-related Macular Degeneration (AMD). The treatment regimen involves administering 120 mg of Dimethyl Fumarate twice daily for the first week, followed by 240 mg twice daily for the subsequent 51 weeks.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Age 55 years of age to 85 years old at the moment of inclusion
- Participant must understand and sign the protocol's informed consent document
- 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
- Participant must have a steady fixation in the study eye in the foveal or parafoveal area and media clear enough for good quality photographs
- Participant must have visual acuity between 20/20 and 20/200 in the affected eye
- 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)
- 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
- No documented history of heart disease, absence of family history of sudden death, and QTc duration within normal value (<480ms)
- Participants must be affiliated to a social security scheme
Exclusion Criteria
- Participant is in another interventional investigational study < 3 months before inclusion
- Participant is unable to comply with study procedures or follow-up visits
- 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)
- Participant with antecedent of neo-vascular AMD
- 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
- Participant has had a vitrectomy on the study eye
- Participant is expected to need ocular surgery during the course of the trial
- Participant has undergone lens removal in the last three months or Yttrium Aluminium Garnet (YAG) laser capsulotomy within the last month
- Participant is on chemotherapy
- Participant is on chronic (more than 3 months) immunosuppressive medication administered via ocular or systemic route(s) or is immunosuppressed
- Participant is on ocular or systemic medications known to be toxic to the lens, retina or optic nerve
- Participant with a history of malignancy that would compromise the 2-year study survival
- Participant with a history of ocular herpes simplex virus (HSV)
- Contra-indications or known hyper-sensibility to Dimethyl Fumarate or experimental treatment excipients
- Severe active gastrointestinal disease
- 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
- Any contraindications to gadolinium including pregnancy, previous allergic reaction, severe kidney disease
- Any contraindications to aspirin
- 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
- Lymphopenia: below normal laboratory values at inclusion
- Severe impairment of a vital organ including severe liver and renal impairment
- Previous organ allograft
- 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)
- 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)
- 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)
- 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.)
- Ocular or peri-ocular inflammation or infection in either eye
- Presence of active or inactive toxoplasmosis in any or both eye(s)
- Presence of active or latent tuberculosis infection
- 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
- Persons under curatorship or guardianship
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 France | Recruiting | 07 Feb 2022 | 90 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
DIMETHYL FUMARATE | Test | — | ORAL USE | 240 | 51 | SUB13608MIG |
DIMETHYL FUMARATE | Test | — | ORAL USE | 120 | 1 | SUB13608MIG |