Age Related Macular DegenerationPhase 1SEIRANCT00726466
Study of Efalizumab Combined With Intravitreal Ranibizumab in the Treatment of Age-Related Macular Degeneration
A Phase 1 study testing Efalizumab, Ranibizumab in people with Age Related Macular Degeneration and AMD, run by Vitreous -Retina- Macula Consultants of New York at 1 site in United States.
Trial summary
Efalizumab is an immunosuppressive recombinant humanized IgG1 monocolonal antibody (150 Kd) that binds to human CD11a (1) and is used for the treatment of plaque psoriasis. Efalizumab was derived from the humanization of the murine efalizuman monoclonal antibody MHM24, which recognizes human and chimpanzee CD11a. Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Age Related Macular Degeneration, AMD, CNV
- What is being tested?
- Efalizumab, Ranibizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2008to not given
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Ability to provide written informed consent and comply with study assessments for the full duration of the study.
- Demonstrate understanding of and ability to perform weekly self sub-cutaneous injections.
- Subjects of either gender, Age > 50 years
- Best corrected visual acuity in the study eye between 20/40 and 20/320.
- Subfoveal choroidal neovascularization, secondary to age related macular degeneration. 6-10 anti-VEGF treatments allowed prior to enrollment.
- Presence of subretinal fluid and/or cystoid retinal edema on OCT.
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- Presence of fibrosis, hemorrhage, serous pigment epithelial detachments, tear (rip) of the retinal pigment epithelium or other hypofluorescent lesions should not obscure greater than 50% of the CNV lesion.
- Annual immunization completed at least 4-6 weeks prior to BSL.
- Clear ocular media and adequate papillary dilation to permit good quality stereoscopic fundus photography
- Ability to return for all study visits
Who cannot join
- Pregnancy (positive pregnancy test) or lactation.
- Premenopausal women not using adequate contraception. The following are considered effective means of contraception: surgical sterilization or use of oral contraceptives, barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel, an IUD, or contraceptive hormone implant or patch.
- Had prior treatment with Photodynamic Therapy (PDT).
- Had treatment with anti-VEGF agents within 30 days prior to BSL.
- Had treatment with Kenalog within 6 months prior to BSL.
- Had treatment with Dexamethaosne within 30 days prior to BSL.
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- Had ocular surgery within the past 60 days in the study eye.
- Concurrent use of more than two therapies for glaucoma.
- Uncontrolled glaucoma in the study eye (defined as intraocular pressure >30 mm Hg despite treatment with anti-glaucoma medication).
- Concurrent use of systemic anti-VEGF agents
- Has active infection in the study eye.
- Inability to obtain photographs to document CNV.
- Has received investigational therapy within 60 days prior to study entry.
- Patients with significantly compromised visual acuity in the study eye due to concomitant ocular conditions.
- Have a history of hypersensitivity to efalizumab or any of its components
- Current or history of prior treatment of psoriasis with subcutaneous efalizumab within 6 months of study entry.
- Have a history of ongoing uncontrolled serious bacterial, viral, fungal, or atypical mycobacterial infection. This includes diagnoses that required more than 2 weeks of therapy, such as endocarditis and osteomyelitis, which have been treated in the past 6 months. In addition, if the subject is currently receiving antibiotics, antivirals, or antifungals for an infection or for suppression or prophylaxis for any diagnosis.
- Have a history of opportunistic infections (e.g. systemic fungal infections, parasites)
- Have the presence or history of malignancy, including lymphoproliferative disorders. Subjects with a history of fully resolved basal or squamous cell skin cancer may be enrolled.
- Have a history of thrombocytopenia, clinically significant hemolytic anemia, or unexplained anemia.
- Have a platelet count < 100,000 cells/uL
- Has other conditions the investigator considers to be sound reasons for exclusion (e.g., lack of motivation, history of poor compliance, concomitant illnesses, personality disorder, mental condition, drug abuse, use of neuroleptics, physical or social condition predicting difficulty in long-term follow-up).
- Patients receiving immunosuppressive agents (including but not limited to cyclosporine, methotrexate, azathioprine, mycophenolate mofetil and systemic steroids) are excluded from the screening visit until study completion
- All acellular, live and live-attenuated vaccines are excluded from 14 days prior to the first dose of efalizumab until a minimum of 4 weeks after the last dose of efalizumab
- Has an allergy to sodium fluorescein dye.
- Inability to comply with study or follow-up procedures.
Trial locations and contacts
1 site in 1 country.
United States1 site
Vitreous Retina Macula Consultants of New York
New York, New York, 10022
About this study
Official title: A Phase I Study of the Inhibition of LFA-1 to Intercellular Adhesion Molecule-1 (ICAM-1) Using Subcutaneous Efalizumab Combined With Intravitreal Ranibizumab in the Treatment of Age-Related Macular Degeneration (SEIRA)
Efalizumab is an immunosuppressive recombinant humanized IgG1 monocolonal antibody (150 Kd) that binds to human CD11a (1) and is used for the treatment of plaque psoriasis. Efalizumab was derived from the humanization of the murine efalizuman monoclonal antibody MHM24, which recognizes human and chimpanzee CD11a. Humanization of MHM24 was accomplished by grafting the murine complementarity determining regions (hypervariable region) into consensus human IgG1/ heavy and light chain sequences (Werther et al 1996). These same consensus human immunoglobulin sequences have been successfully used in the humanization of other murine antibodies, including those targeted to HER2 and IgE. Efalizumab inhibits the binding of LFA-1 to intercellular adhesion molecule-1 (ICAM-1) thereby inhibiting the adhesion of leukocytes to other cell types.
Ranibizumab is a recombinant, humanized, Fab fragment of a mouse monoclonal antibody targeted against VEGF. As VEGF binds to cellular receptors, it stimulates angiogenesis and vascular leakage. Blockade of VEGF by ranibizumab leads to reduced stimulation of cell proliferation and permeability resulting in inhibition of angiogenesis and decreased leakage. Ranibizumab intravitreal administration in neovascular AMD patients has been shown to effectively reduce vascular leakage and growth of CNV and to stabilize or improve visual function.
To further improve visual acuity, a combination therapy using efalizumab and ranibizumab is proposed. Efalizumab could target the adhesion factors that precede angiogenesis and improve the outcome for AMD patients in combination with the anti-VEGF agent, Ranibizumab.
Read the detailed description
This is an open-label, study of 0.5 mg intravitreal dose of Ranibizumab in combination with 1 mg/kg/wk subcutaneous dose of Efalizumab in in subjects with AMD. 10 subjects from 1 site will be enrolled in this study. Subject accrual into the trial is expected to be completed within 6 months.
All subjects will be evaluated monthly with a full ocular examination, visual acuity measurement (ETDRS chart at distance of 4 meters), OCT, and adverse event monitoring. Fluorescein Angiography (FA) and fundus photos will be done at BSL, Months 3, 6, 9 and 12.
Subjects will receive efalizumab 1mg/kg weekly subcutaneous injections for 24 weeks. Subcutaneous Efalizumab injections can be self administered after an initial teaching session in office on Day 0.
Subjects will receive six initial doses of 0.5 mg/eye intravitreous monthly injections of ranibizumab (Day 0, Months 1, 2, 3, 4 and 5) with scheduled follow-up visits monthly for 12 months. Re-treatment after the first six injections will be on an as-needed basis, based on predefined criteria.
3.2 RATIONALE FOR STUDY DESIGN
The rationale for the study is as follows:
- Phase III studies of patients with primary or recurrent choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) treated with repeated intravitreal injections of 0.5 mg of ranibizumab showed evidence for bioactivity, safety, and tolerability (Rosenfeld 2006);
- Phase III studies of patients with chronic moderate to severe plaque psoriasis treated with weekly subcutaneous efalizumab injections of 1mg/kg showed evidence for bioactivity, safety, and tolerability (Dubertret 2006);
- A Phase I study of patients with uveitis treated with subcutaneous efalizumab injections of 1mg/kg in patients with uveitic macular edema is currently enrolling (ClinicalTrials.gov Identifier: NCT00280826)
- Combination therapy of an iCAM-1 inhibitor and an anti-VEGF agent may offer increased treatment benefit in the management of age-related macular degeneration.
- Conditions
- Age Related Macular Degeneration, AMD, CNV
- Being tested
- Efalizumab, Ranibizumab
- Keywords
- Age Related Macular Degeneration, AMD, CNV
- Medical subject headings
- Macular Degeneration
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Efalizumab, RanibizumabDrug
| Study group | Role | What they receive |
|---|---|---|
| I | Experimental | This is an open-label, study of 0.5 mg intravitreal dose of Ranibizumab in combination with 1 mg/kg/wk subcutaneous dose of Efalizumab in in subjects with AMD. Receives: Drug: Efalizumab, Ranibizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
• Safety and tolerability of 0.5 mg intravitreal dose of Ranibizumab in combination with 1 mg/kg/wk subcutaneous dose of Efalizumab in the treatment of age-related macular degeneration using the incidence and severity of adverse events through Month 6.
Secondary outcomes (1)
The secondary outcomes of this study are as follows: • Mean change in ETDRS BCVA at Months 6 and 12. • Mean change in central retinal thickness per OCT at Months 6 and 12 • Mean change in lesion and CNV size as determined by FA at Months 6 and 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Aug 2008 (estimated)
- Study startMar 2008
Why it stopped: Lack of recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Age Related Macular DegenerationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vitreous -Retina- Macula Consultants of New York
- Sponsor type
- University, hospital or other
- Collaborators
- Genentech, Inc.
- Investigators
- Jason S Slakter, MD, Principal investigator, Vitreous -Retina- Macula Consultants of New York
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00726466
- Sponsor's protocol ID
- FVF4385s
- Acronym
- SEIRA
- Status last verified
- Jul 2015
- First submitted
- 29 Jul 2008
- Last updated
- 7 Jul 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Jul 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of the Inhibition of LFA-1 to Intercellular Adhesion Molecule-1 (ICAM-1) Using Subcutaneous Efalizumab Combined With Intravitreal Ranibizumab in the Treatment of Age-Related Macular Degeneration (SEIRA)
- ClinicalTrials.gov ID
- NCT00726466
- Acronym / sponsor ID
- SEIRA / FVF4385s
- Conditions
- Age Related Macular Degeneration, AMD, CNV
- Keywords
- Age Related Macular Degeneration, AMD, CNV
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Lack of recruitment
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Vitreous -Retina- Macula Consultants of New YorkUniversity, hospital or other
- Collaborators
- Genentech, Inc.
- Study start
- Mar 2008
- First posted
- 1 Aug 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Efalizumab is an immunosuppressive recombinant humanized IgG1 monocolonal antibody (150 Kd) that binds to human CD11a (1) and is used for the treatment of plaque psoriasis. Efalizumab was derived from the humanization of the murine efalizuman monoclonal antibody MHM24, which recognizes human and chimpanzee CD11a. Humanization of MHM24 was accomplished by grafting the murine complementarity determining regions (hypervariable region) into consensus human IgG1/ heavy and light chain sequences (Werther et al 1996). These same consensus human immunoglobulin sequences have been successfully used in the humanization of other murine antibodies, including those targeted to HER2 and IgE. Efalizumab inhibits the binding of LFA-1 to intercellular adhesion molecule-1 (ICAM-1) thereby inhibiting the adhesion of leukocytes to other cell types.
Ranibizumab is a recombinant, humanized, Fab fragment of a mouse monoclonal antibody targeted against VEGF. As VEGF binds to cellular receptors, it stimulates angiogenesis and vascular leakage. Blockade of VEGF by ranibizumab leads to reduced stimulation of cell proliferation and permeability resulting in inhibition of angiogenesis and decreased leakage. Ranibizumab intravitreal administration in neovascular AMD patients has been shown to effectively reduce vascular leakage and growth of CNV and to stabilize or improve visual function.
To further improve visual acuity, a combination therapy using efalizumab and ranibizumab is proposed. Efalizumab could target the adhesion factors that precede angiogenesis and improve the outcome for AMD patients in combination with the anti-VEGF agent, Ranibizumab.
Detailed description
This is an open-label, study of 0.5 mg intravitreal dose of Ranibizumab in combination with 1 mg/kg/wk subcutaneous dose of Efalizumab in in subjects with AMD. 10 subjects from 1 site will be enrolled in this study. Subject accrual into the trial is expected to be completed within 6 months.
All subjects will be evaluated monthly with a full ocular examination, visual acuity measurement (ETDRS chart at distance of 4 meters), OCT, and adverse event monitoring. Fluorescein Angiography (FA) and fundus photos will be done at BSL, Months 3, 6, 9 and 12.
Subjects will receive efalizumab 1mg/kg weekly subcutaneous injections for 24 weeks. Subcutaneous Efalizumab injections can be self administered after an initial teaching session in office on Day 0.
Subjects will receive six initial doses of 0.5 mg/eye intravitreous monthly injections of ranibizumab (Day 0, Months 1, 2, 3, 4 and 5) with scheduled follow-up visits monthly for 12 months. Re-treatment after the first six injections will be on an as-needed basis, based on predefined criteria.
3.2 RATIONALE FOR STUDY DESIGN
The rationale for the study is as follows:
- Phase III studies of patients with primary or recurrent choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) treated with repeated intravitreal injections of 0.5 mg of ranibizumab showed evidence for bioactivity, safety, and tolerability (Rosenfeld 2006);
- Phase III studies of patients with chronic moderate to severe plaque psoriasis treated with weekly subcutaneous efalizumab injections of 1mg/kg showed evidence for bioactivity, safety, and tolerability (Dubertret 2006);
- A Phase I study of patients with uveitis treated with subcutaneous efalizumab injections of 1mg/kg in patients with uveitic macular edema is currently enrolling (ClinicalTrials.gov Identifier: NCT00280826)
- Combination therapy of an iCAM-1 inhibitor and an anti-VEGF agent may offer increased treatment benefit in the management of age-related macular degeneration.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| I | Experimental | Drug: Efalizumab, RanibizumabThis is an open-label, study of 0.5 mg intravitreal dose of Ranibizumab in combination with 1 mg/kg/wk subcutaneous dose of Efalizumab in in subjects with AMD. |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Ability to provide written informed consent and comply with study assessments for the full duration of the study.
- Demonstrate understanding of and ability to perform weekly self sub-cutaneous injections.
- Subjects of either gender, Age > 50 years
- Best corrected visual acuity in the study eye between 20/40 and 20/320.
- Subfoveal choroidal neovascularization, secondary to age related macular degeneration. 6-10 anti-VEGF treatments allowed prior to enrollment.
Key exclusion criteria (26 listed)
- Pregnancy (positive pregnancy test) or lactation.
- Premenopausal women not using adequate contraception. The following are considered effective means of contraception: surgical sterilization or use of oral contraceptives, barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel, an IUD, or contraceptive hormone implant or patch.
- Had prior treatment with Photodynamic Therapy (PDT).
- Had treatment with anti-VEGF agents within 30 days prior to BSL.
- Had treatment with Kenalog within 6 months prior to BSL.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Efalizumab, Ranibizumab | Drug | I |
Primary outcome
• Safety and tolerability of 0.5 mg intravitreal dose of Ranibizumab in combination with 1 mg/kg/wk subcutaneous dose of Efalizumab in the treatment of age-related macular degeneration using the incidence and severity of adverse events through Month 6.
1 secondary outcome
The secondary outcomes of this study are as follows: • Mean change in ETDRS BCVA at Months 6 and 12. • Mean change in central retinal thickness per OCT at Months 6 and 12 • Mean change in lesion and CNV size as determined by FA at Months 6 and 12
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jul 2015.
- Study siteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jason S Slakter, MD principal investigator
Vitreous -Retina- Macula Consultants of New York
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Efalizumab, Ranibizumab in people with Age Related Macular Degeneration and AMD, run by Vitreous -Retina- Macula Consultants of New York 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 10 inclusion and 26 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: withdrawn, as of the sponsor's last update on 7 Jul 2015. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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?
• Safety and tolerability of 0.5 mg intravitreal dose of Ranibizumab in combination with 1 mg/kg/wk subcutaneous dose of Efalizumab in the treatment of age-related macular degeneration using the incidence and severity of adverse events through Month 6.. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 7 Jul 2015.