A non-controlled trial of anti-Tumour Necrotising Factor alpha (anti-TNFa) chimeric monoclonal antibody (Infliximab, Remicade®) in exudative age-related macular degeneration
| ISRCTN | ISRCTN01449944 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN01449944 |
| Secondary identifying numbers | OZR-2005-11, NL855 (NTR869) |
- Submission date
- 16/07/2007
- Registration date
- 16/07/2007
- Last edited
- 28/10/2021
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Eye Diseases
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English summary of protocol
Not provided at time of registration
Contact information
Dr P.M. van Hagen
Scientific
Scientific
Erasmus Medisch Centrum
Rotterdam
3015 GD
Netherlands
| Phone | +31 (0)10 463 3438 |
|---|---|
| p.m.vanhagen@erasmusmc.nl |
Study information
| Study design | Non-randomised, non-controlled, clinical trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Non randomised controlled trial |
| Study setting(s) | Not specified |
| Study type | Treatment |
| Scientific title | A non-controlled trial of anti-Tumour Necrotising Factor alpha (anti-TNFa) chimeric monoclonal antibody (Infliximab, Remicade®) in exudative age-related macular degeneration |
| Study objectives | Treatment with Infliximab will reduce loss of visual acuity by 8 letters or better on the ETDRS chart. |
| Ethics approval(s) | Full approval received from the local medical ethics committee (Medisch Ethische ToetsingsCommissie [METC]) on the 12th January 2006 (ref: MEC-2005-249). |
| Health condition(s) or problem(s) studied | Exudative age-related macular degeneration |
| Intervention | Infliximab (5 mg/kg) in saline solution (0.9%) at weeks 0, 2, 6, 14, 22, 30, 38 and 46. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Not Specified |
| Drug / device / biological / vaccine name(s) | Infliximab, Remicade® |
| Primary outcome measure | 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. |
| Secondary outcome measures | 1. Proportional changes in VA using ETDRS chart, measured at baseline, weeks 2, 6, 14, 22, 30, 38, 46, 52 and 72 2. Proportion of target eyes that have a change in VA better than a loss of 15 letters on the ETDRS chart, measured at baseline, weeks 2, 6, 14, 22, 30, 38, 46, 52 and 72 3. Proportion of target eyes that have a change in VA better than a loss of 30 letters on the ETDRS chart, measured at baseline, weeks 2, 6, 14, 22, 30, 38, 46, 52 and 72 4. Time until decrease of VA greater than 15 letters on ETDRS chart, measured at baseline, weeks 2, 6, 14, 22, 30, 38, 46, 52 and 72 5. Time until decrease of VA greater than 30 letters on ETDRS chart, measured at baseline, weeks 2, 6, 14, 22, 30, 38, 46, 52 and 72 6. Change in contrast sensitivity using Pelli-Robson chart, measured at baseline, weeks 2, 6, 14, 22, 30, 38, 46, 52 and 72 7. Change in area of the CNV lesion on photography and fluorescein angiography, measured at weeks 22 and 52 8. Change in quality of life measurements, measured at weeks 6, 22, 38 and 52 (using the 36-item Short Form health survey [SF-36] and the National Eye Institute Visual Function Questionnaire-25 [NEI-VFQ25]) |
| Overall study start date | 01/01/2006 |
| Completion date | 31/12/2007 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Senior |
| Sex | Both |
| Target number of participants | 40 |
| Total final enrolment | 13 |
| Key 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 |
| Key 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, Pneumocystis carinii, aspergillosis, histoplasmosis, or mycobacteria other than TB) within six months prior to screening 11. Are considered ineligible according to the TB eligibility assessment, screening, and early detection of reactivation rules 12. Have a history of lymphoproliferative disease, including lymphoma or signs suggestive of possible lymphoproliferative disease such as lymphadenopathy of unusual size or location (e.g., nodes in the posterior triangle of the neck, infraclavicular, epitrochlear, or periaortic area), or splenomegaly 13. Currently have any known malignancy or have a history of malignancy within the previous five years, with the exception of basal cell or squamous cell carcinoma of the skin that has been fully excised with no evidence of recurrence 14. Have current signs or symptoms of severe, progressive or uncontrolled renal, hepatic, haematological, gastrointestinal, endocrine, pulmonary, cardiac, neurological, or cerebral disease 15. Are unable or unwilling to undergo multiple venipunctures because of poor tolerability or lack of easy access 16. Use of any investigational drug within 30 days prior to screening or within five half-lives of the investigational agent, whichever is longer 17. Treatment with any other therapeutic agent targeted at reducing TNF (e.g., pentoxifylline, thalidomide, etanercept, adalimumab etc.) within three months of screening 18. Presence of a transplanted solid organ (including a corneal transplant) 19. Have a concomitant diagnosis or history of congestive heart failure TB exclusion criteria: 1. Have a history of latent or active granulomatous infection, including TB, histoplasmosis, or coccidioidomycosis, prior to screening 2. Have had a Bacille Calmette-Guerin (BCG) vaccination within 12 months of screening 3. Have a chest radiograph within previous three months that shows an abnormality suggestive of a malignancy or current active infection, including TB 4. Have had a non-tuberculous mycobacterial infection or opportunistic infection (e.g., cytomegalovirus, Pneumocystis carinii, aspergillosis) within six months prior to screening |
| Date of first enrolment | 01/01/2006 |
| Date of final enrolment | 31/12/2007 |
Locations
Countries of recruitment
- Netherlands
Study participating centre
Erasmus Medisch Centrum
Rotterdam
3015 GD
Netherlands
3015 GD
Netherlands
Sponsor information
Erasmus Medical Centre (The Netherlands)
Hospital/treatment centre
Hospital/treatment centre
P.O. Box 2040
Rotterdam
3000 CA
Netherlands
| Website | http://www.erasmusmc.nl/content/englishindex.htm |
|---|---|
"ROR" |
https://ror.org/018906e22 |
Funders
Funder type
Industry
Centocor (The Netherlands)
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan | Not provided at time of registration |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | 22/06/2014 | 28/10/2021 | Yes | No |
Editorial Notes
28/10/2021: The following changes have been made:
1. Publication reference added.
2. The total final enrolment number has been added from the reference.
3. The Netherlands Trial Register registration number has been added to the protocol /serial number.
