Primary To evaluate the efficacy of Pegcetacoplan compared to sham injection in patients with GA secondary to AMD assessed by change in the total area of GA lesions from baseline as measured by FAF.Key SecondaryTo evaluate the efficacy of…
ID
Source
Brief title
Condition
- Ocular structural change, deposit and degeneration NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary Efficacy Endpoint
• Change from baseline to Month 12 in total area of GA lesion(s) in the study
eye (in mm2) based on Fundus Autofluorescence (FAF).
Secondary outcome
Key Secondary Efficacy Endpoints
• Change from baseline in monocular maximum reading speed (study eye), as
assessed by Minnesota Reading (MNRead) or Radner Reading Charts at Month 24 (in
select countries)
• Change from baseline in Functional Reading Independence (FRI) index score, at
Month 24.
• Change from baseline in normal luminance best-corrected visual acuity score
(NL-BCVA) at Month 24 as assessed by ETDRS chart.
Background summary
Age-related macular degeneration is the leading cause of severe vision loss in
people over the age of 65 in the United States and other Western countries.
While there is treatment for exudative AMD with anti-VEGF therapies, no
approved therapy exists for GA which is usually bilateral and relentlessly
progressive. It represents a significant unmet need as it leads to significant
visual impairment and affects more than 5 million people worldwide. Human
biochemical, genetic, and clinical lines of evidence indicate that the
complement system plays a role in the etiology of age-related macular
degeneration (AMD). Pegcetacoplan is a PEGylated cyclic peptide inhibitor of
complement C3. The peptide portion of the drug binds to complement C3 and is a
broad inhibitor of the complement cascade, a biological process that is part of
innate immunity and is involved in multiple inflammatory processes. The
PEGylation of the molecule imparts slower clearance from the vitreous humor
following administration. If efficacious, Pegcetacoplan is expected to alter
the course of GA and slow its rate of progression.
Study objective
Primary
To evaluate the efficacy of Pegcetacoplan compared to sham injection in
patients with GA secondary to AMD assessed by change in the total area of GA
lesions from baseline as measured by FAF.
Key Secondary
To evaluate the efficacy of Pegcetacoplan compared to sham-injection in
patients with GA secondary to AMD with respect to:
o Monocular maximum reading speed (study eye), as assessed by Minnesota Reading
or Radner Reading (MNRead) Charts (in select countries)
o Functional Reading Independence (FRI) index score
o Normal luminance best-corrected visual acuity score (NL BCVA) in the study
eye
Study design
This is a 30-month, Phase III, multicenter, randomized, double-masked,
sham-injection controlled study to assess the efficacy and safety of multiple
IVT injections of Pegcetacoplan in subjects with GA secondary to AMD.
The study will randomize approximately 600 subjects across approximately 100
multinational sites. Subjects will be screened within 28 days before receiving
Pegcetacoplan or Sham injection. Upon entry into the study, subjects will be
assigned a screening number. Subjects who meet all inclusion and none of the
exclusion criteria will return to the clinic for randomization and treatment on
Visit 2 (Day 1). At this visit, subjects will be randomized 2:2:1:1 to receive
APL-2 Monthly, APL-2 Every-Other-Month, Sham injection Monthly or
Sham-injection Every-Other-Month, respectively. Randomization will be
stratified according to GA lesion area at screening (< 7.5 mm2; >= 7.5 mm2), and
presence of CNV in the fellow eye.
All subjects will be assessed monthly during the first 12 months regardless of
treatment regimen. From Month 12 to Month 24, subjects will follow the outlined
visit schedule (45TAppendix A45T to 45TD45T) based on treatment assignment
(i.e. subjects in the monthly groups will be assessed monthly while subjects in
the every-other-month will be assessed every-other-month). Subjects will be
offered entry into an open-label extension study at the end of the 24-month
treatment period.
Intervention
Pegcetacoplan intravitreal injections or sham injections
Study burden and risks
Although the subjects receiving Pegcetacoplan might be at a risk of developing
wet AMD, this can be treated with standard of care anti-VEGF therapies.
Furthermore, the ophthalmic procedures required for participants in this study
might have some risks as well, but these procedures are all standard and widely
performed in ophthalmology.
As there is a potential health benefit for trial participants from receipt of
study drug, i.e. an altered course of GA and slow down of the AMD progression.
This potential health benefits outweighs the risks associated with
participation in this study.
5th Avenue 100
Waltham MA 02451
US
5th Avenue 100
Waltham MA 02451
US
Listed location countries
Age
Inclusion criteria
1. Age >= 60 years.
2. NL-BCVA of 24 letters or better using ETDRS charts.
3. Clinical diagnosis of GA of the macula secondary to AMD as determined by the
Investigator and confirmed by the Reading Center.
4. The GA lesion must meet the criteria as determined by the central reading
center*s assessment of FAF imaging at screening.
5. Adequate clarity of ocular media, adequate pupillary dilation, and fixation
to permit the collection of good quality images as determined by the
Investigator.
6. Meets the criteria related to microperimetry.
7. Female subjects must be women of non-child-bearing potential or women of
child-bearing potential with a negative pregnancy test at screening and must
agree to use protocol defined methods of contraception.
8. Males with female partners of child-bearing potential must agree to use
protocol defined methods of contraception
9. Willing and able to give informed consent and to comply with the study
procedures and assessments.
Exclusion criteria
1. GA secondary to a condition other than AMD such as Stargardt disease, cone
rod dystrophy or toxic maculopathies like plaquenil maculopathy in either eye.
2. Spherical equivalent of the refractive error demonstrating > 6 diopters of
myopia or an axial length >26 mm.
3. Any history or active CNV, associated with AMD or any other cause, including
any evidence of retinal pigment epithelium rips or evidence of
neovascularization anywhere based on SD-OCT imaging and/or fluorescein
angiography as assessed by the Reading Center.
4. Presence in either eye of an active ocular disease that in the opinion of
the Investigator compromises or confounds visual function, including but not
limited to, uveitis, other macular diseases (e.g. clinically significant
epiretinal membrane (ERM), full thickness macular hole or uncontrolled
glaucoma/ocular hypertension. Benign conditions in the opinion of the
investigator such as peripheral retina dystrophy are not exclusionary).
5. Intraocular surgery (including lens replacement surgery) within 3 months
prior to randomization.
6. History of laser therapy in the macular region.
7. Aphakia or absence of the posterior capsule. Note: YAG laser posterior
capsulotomy for posterior capsule opacification done at least 60 days prior to
screening is not exclusionary.
8. Any ocular condition other than GA secondary to AMD that may require surgery
or medical intervention during the study period or, in the opinion of the
Investigator, could compromise visual function during the study period
9. Any contraindication to IVT injection including current ocular or periocular
infection
10. History of prior intravitreal injection in the study eye.
11. Unable to perform microperimetry reliably in the opinion of the
investigator.
12. Prior participation in another interventional clinical study for
intravitreal therapies in either eye (including subjects receiving sham).
13. Prior participation in another interventional clinical study for geographic
atrophy in either eye including investigational oral medication and placebo.
14. Participation in any systemic experimental treatment or any other systemic
investigational new drug within 6 weeks or 5 half-lives of the active
(whichever is longer) prior to the start of study
treatment.
15. Medical or psychiatric conditions that, in the opinion of the investigator,
make consistent follow-up over the 24-month treatment period unlikely, or would
make the subject an unsafe study candidate.
16. Any screening laboratory value (hematology, serum chemistry or urinalysis)
that in the opinion of the Investigator is clinically significant and not
suitable for study participation.
17. Known hypersensitivity to fluorescein sodium for injection or
hypersensitivity to Pegcetacoplan or any of the excipients in Pegcetacoplan
solution.
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 | EUCTR2018-001435-52-NL |
| ClinicalTrials.gov | NCT03525613 |
| CCMO | NL67314.018.18 |