EFFICACY OBJECTIVESThe primary efficacy objective of this study is to evaluate the efficacy of intravitreal injections of 10 mg lampalizumab administered Q4W or Q6W in CFI profile biomarker positive and CFI profile biomarker-negative patients…
ID
Source
Brief title
Condition
- Vision disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary efficacy outcome measure for this study is GA area at 1 year as
assessed by FAF.
Secondary outcome
The secondary efficacy outcome measures for this study over time are as follows:
• Number of scotomatous points assessed by mesopic microperimetry for the
evaluation of the macular functional response
• Change in macular sensitivity as assessed by mesopic microperimetry for the
evaluation of the macular functional response
• GA area as assessed by FAF
• BCVA score as assessed by ETDRS chart at a starting distance of 4 m
• BCVA score as assessed by ETDRS chart under low luminance conditions at a
starting distance of 4 m
• Binocular reading speed as assessed by MNRead charts or Radner Reading Charts
• Binocular critical print size as assessed by MNRead charts or Radner Reading
Charts
• NEI VFQ-25 composite score
• NEI VFQ-25 near activity subscale score
• NEI VFQ-25 distance activity subscale score
• FRI Index score
For further information see page 39-40 of the protocol.
Background summary
Age-related macular degeneration (AMD) is the leading cause of irreversible
blindness in people aged 50 years or older in the developed world. The
majority of the visual loss occurs in the advanced stage of AMD, which has two
clinical forms: a non-exudative form, geographic atrophy (GA), which is
characterized by loss of choriocapillaris, retinal pigment epithelium (RPE),
and photoreceptors; and an exudative or wet form, which is characterized by
choroidal neovascularization (CNV). The prevalence of GA increases
exponentially with age and approximately quadruples per decade beyond 50 years
of age. The estimated prevalence of GA in populations of European ancestry at
70 years of age is 0.70%, rising to 2.91% at 80 years of age and 11.29% at 90
years of age.
Currently, there are no approved treatments to prevent the worsening of GA or
the associated declines in visual function. Consequently, a significant unmet
need exists for the treatment of this serious condition. The Phase III
clinical development plan for lampalizumab is designed to test the efficacy and
safety of lampalizumab in patients with GA secondary to AMD.
Study objective
EFFICACY OBJECTIVES
The primary efficacy objective of this study is to evaluate the efficacy of
intravitreal injections of 10 mg lampalizumab administered Q4W or Q6W in CFI
profile biomarker positive and CFI profile biomarker-negative patients compared
with sham control assessed by change in the GA area from baseline as measured
by FAF.
The secondary efficacy objective of this study is to evaluate the effect of
lampalizumab compared with sham control, with respect to:
• Macular functional response as assessed by mesopic microperimetry
• Best corrected visual acuity (BCVA) as measured by the Early Treatment
Diabetic Retinopathy Study (ETDRS) chart (at a starting distance of 4 m)
• BCVA as measured by ETDRS chart (at a starting distance of 4 m) under low
luminance conditions
• Binocular reading speed as assessed by the Minnesota Low-Vision Reading Test
(MNRead) or by Radner Reading Charts
• Binocular critical print size as assessed by the MNRead or by Radner Reading
Charts
• Patient-reported visual function as assessed by the National Eye Institute
Visual Functioning Questionnaire 25-item Version (NEI VFQ-25)
• Patient-reported independent reading as assessed by the Functional Reading
Independence Index (FRI Index)
SAFETY OBJECTIVES
The safety objectives for this study are as follows:
• To evaluate the local and systemic safety and tolerability of intravitreal
injections of 10-mg lampalizumab administered Q4W or Q6W relative to sham
control
• To evaluate the clinical significance of anti-therapeutic antibodies directed
against lampalizumab
PHARMACOKINETIC OBJECTIVE
The PK objective for this study is to characterize the systemic PK of
lampalizumab administered by 10-mg intravitreal injections Q4W or Q6W.
DIAGNOSTIC OBJECTIVE
A diagnostic objective for this study is to evaluate the prognostic value of
the CFI profile biomarker on the mean change in the GA area from baseline as
measured by FAF.
EXPLORATORY OBJECTIVES
The exploratory objectives for this study are as follows:
• To evaluate the effect of lampalizumab compared with sham control, with
respect to:
- Monocular reading speed as assessed by MNRead charts or by Radner Reading
Charts
- Monocular critical print size as assessed by MNRead charts or by Radner
Reading Charts
- Monocular reading acuity as assessed by MNRead charts or by Radner Reading
Charts
- Binocular reading acuity as assessed by MNRead charts or by Radner Reading
Charts
• To evaluate the aqueous levels of total lampalizumab and factor D following
intravitreal injection
• To evaluate the potential association of genetic variants in CFI and
complement pathway genes with disease characteristics and response to
administration of lampalizumab
• To evaluate the relationship of genetic variants in CFI and
complement-pathway genes to levels in the blood of messenger RNA (mRNA) and
proteins of CFI and complement-pathway genes.
Study design
This study is a Phase III, double-masked, multicenter, randomized, sham
injection controlled study evaluating the efficacy and safety of a 10-mg dose
of lampalizumab administered Q4W or Q6W by intravitreal injections for
approximately 96 weeks, excluding screening period, in patients with GA
secondary to AMD.
Intervention
Patients that participate in the study will be treated with lampaluzimab or a
sham injection in a Q4Q or Q6W dosing schedule
Study burden and risks
The patient can experience side effects from the medicine or procedures that
are used in this study. The side effects can vary from light to very serious
and will differ from person to person. Everyone that participates in this study
is closely monitored on possible side effects. The sponsor, investigator and
other physicians do not know all side effects that might occur. The
investigator can prescribe the patient medication to help decrease the side
effects. A lot of side effects disappear when the cause of the side effects is
taken away. In some cases side effects may be severe, persist or never
disappear. There is a risk of death. In a recently completed study patients
with GA received an injection every month or every other month. The experience
retrieved in that study show that administration of injections with lapalizumab
were well tolerated over time.
SIDE EFFECTS FROM WHICH IS KNOWN TO BE RELATED TO INJECTION OF THE STUDY
MEDICATION (LAMPATIZUMAB) AND OR INJECTION IN THE EYE
There are events that have been reported by a small number of patients after
the use of lampalizumab in previous clinical trials. These events, which have
been seen with other injections into the eye, have also been seen with use of
lampalizumab. The frequencies listed below are based on use of lampalizumab in
a total of 147 patients, who were enrolled in prior clinical trials.
Very Common (Occur in at least 1 in 10 patients treated):
• Bleeding of the thin membrane covering the white of the eye and inner lid,
• Temporary increase in the pressure in the eye, and
• Eye pain
Common (Occur in at least 1 in 100 to 1 in 10 patients treated):
• Eye irritation,
• Swelling of the thin membrane covering the white of the eye and inner lid,
• Feeling that there is something in the eye,
Uncommon (Occur in at least 1 in 1000 to 1 in 100 patients treated):
• A serious eye infection called endophthalmitis
SIDE EFFECTS THAT ARE POSSIBLY RELATED WITH INJECTIONS OF THE STUDY MEDICATION
(LAMPALUZIMAB) AND/OR INJECTION IN THE EYE COMPLICATIONS RELATED TO THE EYE
There is a change that your eyesight worsens; this can be caused due to
worsening of your eye disease, due to a side effect of the injection with the
study treatment or other causes. The study medication can cause infections in
the eye that cans how as redness, swelling or pain in the eye. This infection
does not have to be related with bacteria. The study medication can increase
your risk of certain bacterial infections in the eye; until now this risk is
not observed in previous studies with the study medication in animals or
humans. The injection of the study medication in the eye can also cause side
effects. In these cases it concerns detachment of the retina of the underlying
pigment layer or clouding of the lens (cataract), or temporary loss of vision
due to an increase in the pressure within the eye. In a few patients, release
of ocular fluid by a needle was necessary to reduce the eye pressure and
resolve the temporary vision loss.
For further information see addendum 2 of the patient information.
Beneluxlaan 2a
Woerden 3446 GR
NL
Beneluxlaan 2a
Woerden 3446 GR
NL
Listed location countries
Age
Inclusion criteria
- Willingness and the ability to provide signed informed consent; additionally, at U.S. sites, patients must provide Health Insurance Portability and Accountability Act (HIPAA) authorization, and in other countries, as applicable according to national laws.
- Participants aged >= 50 years.
Ocular Inclusion Criteria: Study Eye.
- Well demarcated area(s) of GA secondary to AMD with no evidence of prior or active choroidal neovascularization (CNV)
- BCVA letter score superior or equal to 49 letters (Snellen equivalent of 20/100 or better) using ETDRS at starting distance of 4m
- If BCVA letter score is superior or equal to 79 letters (Snellen equivalent of 20/25 or better), at least one GA easion must be within 250 micrometers of the foveal centre.
Exclusion criteria
GA Characteristics Exclusion Criteria
- GA in either eye due to causes other than AMD (monogenetic macular dystrophies [e.g., Stargardt disease, cone rod dystrophy] or toxic
maculopathies [e.g., chloroquine/hydroxychloroquine maculopathy]);Ocular Exclusion Criteria: Study Eye
- History of vitrectomy surgery, submacular surgery, or any other surgical intervention for AMD
- Previous laser photocoagulation for CNV, diabetic macular edema, retinal vein occlusion, and proliferative diabetic retinopathy
- Prior treatment with Visudyne®, external-beam radiation therapy (for intraocular conditions), or transpupillary thermotherapy
- History of prophylactic subthreshold laser treatment for AMD
- Previous intravitreal drug delivery (e.g., intravitreal corticosteroid injection, anti-angiogenic drugs, anti-complement agents, or device
implantation). A single intraoperative administration of a corticosteroid during cataract surgery for cystoid macular edema prophylaxis at least 3
months prior to screening is permitted.;Ocular Exclusion Criteria: Non-study eye
- Non-functioning non-study eye defined as either: BCVA of hand motion or worse OR no physical presence of non-study eye
(i.e., monocular);Ocular Exclusion Criteria: Both eyes
- Previous participation in interventional clinical trials for geographic atrophy or dry AMD (except of vitamins and minerals) irrespective of the
route of administration (ocular or systemic)
- Previous treatment with eculizumab, lampalizumab, fenretidine or any other drugs for geographic atrophy or dry AMD treatment;Concurrent Systemic Conditions Exclusion Criteria
- Uncontrolled blood pressure (defined as systolic >180 mm Hg and/or diastolic >110 mm Hg while patient is sitting) If a patient's initial
measurement exceeds these values, a second reading may be taken 30 or more minutes later. If the patient's blood pressure must be
controlled by anti hypertensive medication, the patient can become eligible if medication is taken continuously for at least 30 days prior to
Day 1.
- History of other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding that gives reasonable suspicion of a
disease or condition that contraindicates the use of lampalizumab or that might affect interpretation of the results of the study or that renders the
patient at high risk of treatment complications
- Treatment for active systemic infection or localized infection. The ongoing prophylactic use of antimicrobial therapy should be discussed
with the Medical Monitor.
- Predisposition or history of increased risk of infection
- Active malignancy within past 12 months except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma
and prostate cancer with a Gleason score of < 6 and a stable prostate specific antigen (PSA) for > 12 months.
- History of allergy to fluorescein that is not amenable to treatment
- History of a severe allergic reaction or anaphylactic reaction to a biologic agent or known hypersensitivity to any component of the
lampalizumab injection
- Inability to comply with study or follow-up procedures
- Inability to obtain CFP, FAF, and FA of sufficient quality to be analyzed and graded by the central reading center
- Previous participation in any studies of investigational drugs within 3 months (except as listed in protocol section 4.1.2d) preceding Day 1
(excluding vitamins and minerals)
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2014-000107-27-NL |
| ClinicalTrials.gov | NCT02247479 |
| CCMO | NL50409.018.14 |