A non-controlled trial of anti-Tumour Necrotising Factor alpha (anti-TNFa) chimeric monoclonal antibody (Infliximab, Remicade®) in exudative age-related macular degeneratio

Not Applicable

Completed

• Conditions: Exudative age-related macular degeneration; Eye Diseases; Disorders of choroid and retina

• Registration Number: ISRCTN01449944
• Lead Sponsor: Erasmus Medical Centre (The Netherlands)

Brief Summary

2014 Results article in https://pubmed.ncbi.nlm.nih.gov/24953977/ (added 28/10/2021)

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2007-07-16
• Study Completion: 2007-12-31
• Last Update Posted: 8 November 2021

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 13

Inclusion Criteria

1. Have the capacity to understand and sign an informed consent form
2. Men and women older than 60 years of age
3. Women must be postmenopausal (no menstrual period for a minimum of one year) or surgically sterilised. Men must agree to use adequate birth control measures during the study and for six months after the last infusion of infliximab
4. A decrease in visual acuity within two months prior to study start, related to exudative ARMD, with an occult or a mixed (minimally classic) Choroid Neovascularisation (CNV) that is at least partially subfoveal (i.e. on fluorescein angiogram, an occult or predominantly occult CNV is shown, within 200 µm of the centre of the Foveal Area Zone [FAZ])
5. A best corrected visual acuity (distance) of 0.125 (20/160 snellen equivalent, 0.9 logmar ETDRS equivalent or 40 letters read on ETDRS chart) or better in the study eye, which has been determined within one week prior to randomisation and first treatment. Visual acuities will be measured using ETDRS charts at the moment of screening and during every visit of the study
6. The screening laboratory test results must meet the following criteria:
6.1. White Blood Cells (WBC): greater than or equal to 3.5 x 10^9/L
6.2. Haemoglobin for males greater than or equal to 8.6 mmol/L and females greater than or equal to 7.5 mmol/L
6.3. Platelets 150 - 350 x 10^9/L
6.4. Serum creatinine less than 120 mmol/L or 1.5 times the upper limit of the normal range
6.5. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) should be within three times the upper limit of the normal range
7. Are considered eligible according to the Tuberculosis (TB) eligibility assessment, screening, and early detection of reactivation rules

TB inclusion criteria:
1. Have no history of latent or active TB prior to screening
2. Have no signs or symptoms suggestive of active TB upon medical history and/or physical examination
3. Have had no recent close contact with a person with active TB or, if there has been such contact, will be referred to a physician specialising in TB to undergo additional evaluation and, if warranted, receive appropriate treatment for latent TB prior to or simultaneously with the first administration of study agent
4. Within one month prior to the first administration of study agent, either have a negative tuberculin skin test, or have a newly identified positive tuberculin skin test during screening in which active TB has been ruled out and for which appropriate treatment for latent TB has been initiated either prior to or simultaneously with the first administration of study agent
5. Have a chest radiograph (both posterior-anterior and lateral views), taken within three months prior to the first administration of study agent and read by a qualified radiologist, with no evidence of current active TB or old inactive TB

Exclusion Criteria

Ophthalmic exclusion criteria:
1. Inability to visualise the fundus due to corneal or important lenticular opacities
2. Inability to obtain photographs to document CNV, e.g. due to allergy to fluorescein dye, Indocyanine Green (ICG) or lack of venous access
3. Have a history of treatment for CNV in the study eye: including but not limited to confluent laser photocoagulation, submacular surgery, radiotherapy or macular scatter ('grid') laser photocoagulation
4. Patients requiring ocular surgery within the initial 12 months of treatment, or who have had surgery in the prior three months
5. Are participating in another ophthalmic clinical trial requiring follow-up examinations or are receiving, or have received any experimental systemic treatment for ARMD (e.g. retinoic acid, thalidomide) or any other investigational drug within 12 weeks prior to the start of study treatment
6. Are subject to laser coagulation, acetazolamide, high dose systemic steroids (greater than 10 mg prednisolone daily or equivalent) or immunosuppressive therapy
7. Have a tear (rip) of the Retinal Pigment Epithelium (RPE), a vitelliform-like lesion of the outer retina (e.g. as in pattern dystrophies or basal laminar drusen) or central serous retinopathy
8. Have any additional ocular diseases which have irreversibly compromised or, during follow-up, could likely compromise the visual acuity of the study eye including amblyopia, uncontrolled glaucoma in one or both eyes (intraocular pressure greater than 30 mmHg), anterior ischemic optic neuropathy, diabetic macular oedema, diabetic retinopathy
9. Other retinal or ophthalmic disorders that could influence the macular area
10. Previous retinal surgery
11. High myopia (greater than 8 dioptres)
12. History of macula affecting drugs (hydrochloroquine, chloroquine)

General medical exclusion criteria:
1. Women who are pregnant, nursing, or planning pregnancy within six months after the last infusion (this includes father's who plan on fathering a child within six months after their last infusion)
2. Known allergy against infliximab, fluorescein dye, ICG dye
3. Use of other systemic anti-inflammatory medication except Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) and low dose systemic steroids (equal or less than 10 mg daily prednisolone or equivalent)
4. Have had any previous treatment with monoclonal antibodies or antibody fragments
5. History of receiving human/murine recombinant products or a known allergy to murine products
6. Documentation of seropositive for Human Immunodeficiency Virus (HIV)
7. A positive test for hepatitis B surface antigen or hepatitis C
8. Have a history of alcohol or substance abuse within the preceding six months that, in the opinion of the investigator, may increase the risks associated with study participation or study agent administration, or may interfere with interpretation of results
9. Have a known history of serious infections (e.g., hepatitis, pneumonia or pyelonephritis) in the previous three months
10. Have or have had an opportunistic infection (e.g., herpes zoster [shingles], cytomegalovirus, Pneumocysti

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Absolute change in Visual Acuity (VA) versus baseline of the target eye. Target eye for primary endpoint is defined as the eye that is indicated by the patient as the most recent and worsening. VA change will be expressed as the absolute change in number of letters correctly identified at week 0 compared to week 52.