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Age-Related Macular DegenerationPhase 2AMDB1NCT00304954

Infliximab, Sirolimus and Daclizumab to Treat Age-Related Macular Degeneration

A Phase 2 study testing Intravenous Daclizumab, Intravenous Infliximab and Observation in people with Age-Related Macular Degeneration and Choroidal Neovascularization, run by National Eye Institute (NEI) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This study examined whether the anti-inflammatory medicines infliximab, sirolimus or daclizumab, when given with a participant's current therapies, would prevent the growth of new blood vessels in the eye in participants with age-related macular degeneration (AMD). Read more about this study

Who is it for?
Ages 55 to 92 years
What is being tested?
Intravenous Daclizumab, Intravenous Infliximab and Observation
Could I receive a placebo?
No, everyone receives an active treatment
How many people
13 participants
Where
1 siteUnited States
Study dates
Feb 2006to Jan 2010
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 55 to 92 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Understand and sign the institutional review board (IRB)-approved informed consent document for the study.
  • Age greater than 55 years.
  • In the study eye, diagnosis of AMD defined by the presence of drusen larger than 63 microns.
  • Any anti-angiogenic therapy in the study eye within 7 days of beginning immunosuppressive therapy.
  • In the study eye, the participant's study eye vision is between 20/20 and 20/400.
  • In the study eye, the presence of CNV under the fovea determined by the investigators and defined as any one of the following fluorescein angiographic (FA) features:
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  • Early stippled hyperfluorescence of flat retinal pigment epithelium (RPE)and little or mild leakage in the late frames of the fluorescein (occult).
  • Irregular elevation of the RPE that does not exhibit discrete or bright hyperfluorescence in the early transit phase of the angiogram. Stippled hyperfluorescence may be present. Late frames may show persistent fluorescein staining or leakage within a sensory retinal detachment overlying this area (occult).
  • Late-phase leakage of undetermined source with leakage at the level of the RPE in the late-phase frames of the angiogram in which the source of the late leakage cannot be determined from earlier-phase frames of the angiogram (occult).
  • A well-demarcated area of bright hyperfluorescence in the early phase of the angiogram with leakage through the mid- and late-phase frames which obscures the boundaries of the area (classic).
  • For all CNV lesions considered to have occult CNV with no classic CNV, one of the following criteria must be met:
  • A documented loss of visual acuity (5 or more letters of best-corrected visual acuity if both measurements are made using an Early Treatment for Diabetic Retinopathy Study (ETDRS) chart or, a doubling of the visual angle if Snellen acuities are available from either an outside referral center or within the participating center (e.g., 20/80 to 20/160) a doubling of the visual angle is required because of the measurement variability of Snellen acuities).
  • OR
  • Documented FA evidence of a 10% increase in the lesion greatest linear dimension over the 3 months prior to enrollment.
  • OR
  • Documented blood associated with CNV.
  • The greatest linear dimension of the entire lesion (classic CNV, occult CNV and any features that could obscure the identification of classic or occult CNV) has to be less than or equal to 5400 microns in greatest linear dimension on the retina as measured by the treating ophthalmologist.
  • Retinal photographs and angiography of sufficient quality, allowing assessment of the macular area according to standard clinical practice, can be obtained.
  • Women of childbearing potential must not be pregnant or lactating, must have a negative pregnancy test at screening and must be practicing an adequate method of birth control. Acceptable methods of birth control include intrauterine device (IUD); oral, dermal, implanted or injected contraceptives; tubal ligation; and barrier methods with spermicide.
  • Willingness to comply with the protocol.

Who cannot join

  • CNV, in the study eye, associated with other ocular diseases such as pathologic myopia, ocular histoplasmosis or posterior uveitis, etc.
  • Presence of geographic atrophy under the fovea in the study eye.
  • Evidence of retinal angiomatous proliferation as suspected by the presence of intraretinal hemorrhage, intraretinal leakage, adjoining serous pigment epithelial detachment (PED) or the presence of a connecting retinal vessel.
  • The presence of a chorio-retinal anastomosis.
  • Decreased vision, in the study eye, due to retinal disease not attributable to CNV, such as nonexudative forms of AMD, geographic atrophy, inherited retinal dystrophy, uveitis or epiretinal membrane. Participants who have any additional ocular diseases that have irreversibly compromised or, during follow-up, could likely compromise the visual acuity (VA) of the study eye including amblyopia, anterior ischemic optic neuropathy, clinically significant diabetic macular edema, severe non-proliferative diabetic retinopathy, or proliferative diabetic retinopathy.
  • Decreased vision, in the study eye, due to significant media opacity such as corneal disease or cataract, or opacity precluding photography of the retina; a tear (rip) of the RPE; a vitelliform-like lesion of the outer retina (e.g., as in pattern dystrophies or basal laminar drusen), idiopathic parafoveal telangiectasis, or central serous retinopathy.
Show all 33Show fewer
  • Presence of fibrosis, hemorrhage, pigment epithelial detachments and other hypofluorescent lesions obscuring greater than 50% of the CNV lesion.
  • History of other systemic antiangiogenic treatment or treatment for CNV (not including photodynamic therapy and pegaptanib sodium injections) in the study eye with transpupillary thermotherapy or other local treatment (such as submacular surgery). Previous laser photocoagulation therapy is acceptable, provided it was not subfoveal.
  • Participant with a known underlying systemic disease with evidence of serious or potentially lethal uncontrolled active disease in one or more extraocular organ systems for which a defined effective medical regimen is indicated.
  • Participant with a corneal melting, necrotizing keratitis, or impending vision loss.
  • Participants with history of allergy to/or exposure to mouse protein.
  • Participant with scleritis of infectious etiology.
  • Participant receiving any other investigational therapy or another anti-tumor necrosis factor (TNF) agent that would interfere with the ability to evaluate the safety or efficacy of infliximab.
  • Participant has significant active infection requiring hospitalization.
  • Participant with multiple sclerosis.
  • Participant has severe (class 3/4) congestive heart failure.
  • Participant has a history of cancer within the past 5 years other than basal or squamous cell carcinoma.
  • Participant is pregnant or lactating.
  • Participant with posterior scleritis.
  • Participant has evidence of liver disease (any etiology). History of moderate to severe abnormal liver function, unless documented evidence of normal liver enzymes is provided.
  • Participant has positive PPD (tuberculosis test) unless cleared by Internal Medicine.
  • Participant has positive Chest X-ray showing acute pulmonary disease.
  • Participant has unexplained hematuria.
  • Participant has a history of alkylating therapy use.
  • Current exam evidence of ocular toxoplasmosis; pseudoexfoliation; external ocular infection, including conjunctivitis; chalazion; significant blepharitis; or aphakia in the study eye (pseudophakic participants are eligible).
  • Intraocular surgery (including lens replacement surgery) within 6 weeks prior to randomization.
  • Recent history of (within the last 6 months), or current acute ocular or periocular infection (including any history of ocular herpes zoster or simplex).
  • Known hypersensitivity/allergy to verteporfin, porfimer sodium, or other porphyrins, porphyria or other porphyrin sensitivity, or hypersensitivity to sunlight or bright artificial light. Participation in any other clinical study or are receiving, or have received any experimental systemic treatment for AMD (e.g., retinoic acid, thalidomide). Local therapy for AMD is permitted.
  • Medical problems that make consistent follow-up over the treatment period unlikely (e.g., stroke, severe myocardial infarction (MI), end stage malignancy), any contraindications to performing the necessary diagnostic studies (i.e., known allergy to fluorescein dyes etc.), or in general a poor medical risk because of other systemic diseases or active uncontrolled infections.
  • Participant has a history of moderate to severe abnormal liver function, unless documented evidence of normal liver enzymes is provided.
  • Participant has a history of active pulmonary tuberculosis.
  • Participant has a history of active viral hepatitis.
  • Participant has chronic continued Ketoconazole use.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • National Institutes of Health Clinical Center, 9000 Rockville Pike

    Bethesda, Maryland, 20892

Other trials in United States

About this study

Official title: Treatment of Choroidal Subretinal Neovascularization With Agents Directed Against the Immune Response

This study examined whether the anti-inflammatory medicines infliximab, sirolimus or daclizumab, when given with a participant's current therapies, would prevent the growth of new blood vessels in the eye in participants with age-related macular degeneration (AMD).

Participants 55 years of age and older with AMD and drusen larger than 63um may be eligible for this study. Vision in the study eye was between 20/20 and 20/400.

Read more

Participants were randomly assigned to one of three treatments - infliximab, sirolimus, or daclizumab - or to observation only. In addition, participants may have been treated by their ophthalmologist as needed for their AMD.

Infliximab and daclizumab were given intravenously (through a vein); infusions were given at enrollment in the study, then at 2 weeks, and then monthly.

Sirolimus was a pill that was taken every other day for the duration of the study. At 6 months, participants were evaluated to see whether continuing treatment would be beneficial.

In addition to treatment or observation, participants underwent the following procedures:

Physical examination at enrollment and 6 months.

Photographs of the back of the eye, fluorescein angiography, indocyanine green angiography and measurement of retinal thickness at enrollment and months 1, 3 and 6.

  • Fluorescein angiography evaluated the eye's blood vessels. A yellow dye was injected into an arm vein and traveled to the blood vessels in the eyes. Pictures of the retina were taken using a camera that flashed a blue light into the eye. The pictures show if any dye has leaked from the vessels into the retina, indicating possible blood vessel abnormality.
  • Indocyanine green angiography identified feeder vessels that may have supplied abnormal blood vessels. This procedure is similar to fluorescein angiography, but uses a green dye and flashes an invisible light.
  • Optical coherence tomography measures retinal thickness. This test shines a light into the eye and produces cross-sectional pictures of the retina. These measurements are repeated during the study to determine whether retinal thickening is getting better or worse, or staying the same.

Tuberculin skin test and chest x-ray at enrollment and 6 months.

Blood tests at enrollment and months 1, 3 and 6.

Read the detailed description

There has been much interest in the possible role of the immune system in AMD. Experimental models and patient material have, to date, suggested a role for macrophages and complement. This study hypothesized that the underlying mechanism that leads to choroidal neovascularization (CNV) is similar to those at play in atherosclerosis. If this is the case, the investigators believed that CNV treatment should be amenable to new immunomodulatory agents directed against specific parts of the immune system.

After therapy with anti-angiogenic agents not leading to a persistent remission of CNV due to AMD, participants were treated with one of three immunomodulatory agents or were observed in conjunction with their continued anti-angiogenic therapy. Thus the participant continued with the anti-angiogenic therapy they received after randomization. The investigators hypothesized that this combination therapy would inhibit progression of CNV associated with AMD.

This was an open-label, phase II, randomized, single center clinical trial of 18 study participants randomized to receive one of three immunomodulatory agents or was observed in conjunction with their anti-angiogenic therapy.

Being tested
Intravenous Daclizumab, Intravenous Infliximab, Observation, Oral Rapamycin
Keywords
Age-Related Macular Degeneration, Rapamycin, Remicade, Daclizumab, Immunosuppression, Infliximab, Choroidal Neovascularization, Sirolimus, AMD, Ocular Inflammation
Medical subject headings
Macular Degeneration, Choroidal Neovascularization

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Intravenous DaclizumabDrug

    Also called Zenapax

    Participants randomly assigned to intravenous (IV) daclizumab received 8 mg/kg of IV daclizumab at baseline, then 4 mg/kg of IV daclizumab at Week 2 and then 2 mg/kg of IV daclizumab monthly for the rest of the 6-month study.

  • Intravenous InfliximabDrug

    Also called Remicade

    Participants randomized to IV infliximab received 3 mg/kg of IV infliximab monthly for 6 months.

  • ObservationOther

    Participants randomly assigned to the observation group were given injections of either bevacizumab (1.25 mg/0.05 mL or 2.5 mg/0.1 mL) or ranibizumab (0.5 mg) if they presented with recurrence of intraretinal or subretinal fluid as seen on Stratus Optical Coherence Tomography.

  • Oral RapamycinDrug

    Also called Sirolimus

    Participants randomly assigned to rapamycin received 2 mg in capsule form every other day for 6 months.

Study groups in NCT00304954
Study groupRoleWhat they receive
Intravenous DaclizumabActive comparatorParticipants randomly assigned to intravenous (IV) daclizumab received 8 mg/kg of IV daclizumab at baseline, then 4 mg/kg of IV daclizumab at Week 2 and then 2 mg/kg of IV daclizumab monthly for the rest of the 6-month study.
Receives: Drug: Intravenous Daclizumab
Intravenous InfliximabActive comparatorParticipants randomized to IV infliximab received 3 mg/kg of IV infliximab monthly for 6 months.
Receives: Drug: Intravenous Infliximab
Oral RapamycinActive comparatorParticipants randomly assigned to rapamycin received 2 mg in capsule form every other day for 6 months.
Receives: Drug: Oral Rapamycin
ObservationOtherParticipants randomly assigned to the observation group were given injections of either bevacizumab (1.25 mg/0.05 mL or 2.5 mg/0.1 mL) or ranibizumab (0.5 mg) if they presented with recurrence of intraretinal or subretinal fluid as seen on Stratus Optical Coherence Tomography.
Receives: Other: Observation

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Monthly Rates of Anti-VEGF (Vascular Endothelial Growth Factor) Injections

    Measured: 24 Weeks

Secondary outcomes (2)

  1. Changes in Best-corrected Visual Acuity (BCVA) as Measured by the Standard Early Treatment Diabetic Retinopathy Study (ETDRS) Protocol From Baseline to 24 Weeks

    The values in the table represent the denominator for the visual acuity in feet. A value of 20 represents "normal" 20/20 vision while increasing values for the denominator represent worsening vision.

    Measured: Baseline and 6 months (24 weeks) - Baseline and 3.5 months for Patient 7

  2. Changes in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) From Baseline to 24 Weeks

    Measured: Baseline and 6 months (24 weeks) - Baseline and 3.5 months for Patient 7

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Mar 2006 (estimated)
  2. Study startFeb 2006
  3. Primary completionJan 2010
  4. Study completionJan 2010

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
13 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00304954
Sponsor's protocol ID
060111
Other IDs
06-EI-0111
Acronym
AMDB1
Status last verified
Nov 2016
First submitted
17 Mar 2006
Last updated
29 Nov 2016
Data monitoring committee
Yes

Publications

  • Aeberli D, Oertle S, Mauron H, Reichenbach S, Jordi B, Villiger PM. Inhibition of the TNF-pathway: use of infliximab and etanercept as remission-inducing agents in cases of therapy-resistant chronic inflammatory disorders. Swiss Med Wkly. 2002 Jul 27;132(29-30):414-22. doi: 10.4414/smw.2002.10031.

    PubMed 12428187

  • Antoni C, Dechant C, Hanns-Martin Lorenz PD, Wendler J, Ogilvie A, Lueftl M, Kalden-Nemeth D, Kalden JR, Manger B. Open-label study of infliximab treatment for psoriatic arthritis: clinical and magnetic resonance imaging measurements of reduction of inflammation. Arthritis Rheum. 2002 Oct 15;47(5):506-12. doi: 10.1002/art.10671.

    PubMed 12382299

  • Bian ZM, Elner SG, Strieter RM, Kunkel SL, Lukacs NW, Elner VM. IL-4 potentiates IL-1beta- and TNF-alpha-stimulated IL-8 and MCP-1 protein production in human retinal pigment epithelial cells. Curr Eye Res. 1999 May;18(5):349-57. doi: 10.1076/ceyr.18.5.349.5353.

    PubMed 10372996

  • Nussenblatt RB, Byrnes G, Sen HN, Yeh S, Faia L, Meyerle C, Wroblewski K, Li Z, Liu B, Chew E, Sherry PR, Friedman P, Gill F, Ferris F 3rd. A randomized pilot study of systemic immunosuppression in the treatment of age-related macular degeneration with choroidal neovascularization. Retina. 2010 Nov-Dec;30(10):1579-87. doi: 10.1097/IAE.0b013e3181e7978e.

    PubMed 20847709

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Intravenous Daclizumab, Intravenous Infliximab and Observation in people with Age-Related Macular Degeneration and Choroidal Neovascularization, run by National Eye Institute (NEI) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Nov 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 Apr 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Monthly Rates of Anti-VEGF (Vascular Endothelial Growth Factor) Injections (time frame: 24 Weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00304954, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Nov 2016.

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