The purpose of this study is to investigate the efficacy, safety, durability, and pharmacokinetics of faricimab administered at up to 16-week intervals to treatment-naive patients with nAMD.
ID
Source
Brief title
Condition
- Retina, choroid and vitreous haemorrhages and vascular disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary Efficacy Objective:
To evaluate the efficacy of IVT injections of the 6-mg dose of faricimab on
BCVA outcomes compared with aflibercept
Corresponding Endpoint:
Change from baseline in BCVA (as measured on the ETDRS chart at a starting
distance of 4 meters) based on an average at Weeks 40, 44, and 48
Secondary outcome
To evaluate the ocular and non-ocular
safety and tolerability of faricimab
To evaluate the efficacy of faricimab on
patient-reported vision-related functioning
and quality of life using the NEI VFQ-25
To characterize the systemic
pharmacokinetics of faricimab
For a full list, please see protocol section 2
Background summary
Currently available and approved injection-based treatments for nAMD, such as
aflibercept, only target VEGF. These medications can improve outcomes in
patients with nAMD, but frequent treatments are required and not everyone
responds to treatment. Studies have shown that Ang-2 may also play an
important role in nAMD. Therefore, for some patients, blocking both VEGF and
Ang-2 may be more effective and may also allow for treatments to be given less
frequently.
Study objective
The purpose of this study is to investigate the efficacy, safety, durability,
and pharmacokinetics of faricimab administered at up to 16-week intervals to
treatment-naive patients with nAMD.
Study design
Approximately 640 patients will be enrolled globally and randomized in a 1:1
ratio to one
of two treatment arms:
* Group 1 will receive faricimab, given as an injection in the study eye every
4 weeks for the first 4 injections and then every 8, 12, or 16 weeks for 2
years. The frequency of injections in the first year will be decided on the
basis of the condition of the study eye at Weeks 20 and 24. In Year 2, the
frequency of injections may be changed based on the condition of the eye, but
injections will still be given every 8, 12, or 16 weeks.
* Group 2 will receive aflibercept given as an injection in the study eye every
4 weeks for the first 3 injections and then every 8 weeks for 2 years.
Patients in both treatment arms will complete scheduled study visits Q4W for
the entire study duration (112 weeks). A sham procedure will be administered to
patients in both treatment arms at study visits with no study treatment
administration to maintain masking among treatment arms
Intervention
Patietns taking part in the study will be treated with faricimab or aflibercept
every 4 weeks, with possible sham injections
Study burden and risks
Patients will have to come to the research center every 4 weeks for treatment
or sham treatment. This is a higher number of visits and injections, or sham
injections than standard care. This is necessary to maintain the blinding
between different treatment periods. Roche offers a taxi service to bring the
patients to and from home.
The combined evidence from the Phase II studies BP29647 and CR39521 indicates
that the 6-mg dose of faricimab can be administered to patients with nAMD at
various treatment intervals (Q4W, Q8W, Q12W, and Q16W) to deliver similar
efficacy compared with 0.5 mg of ranibizumab Q4W, and importantly, has the
potential to be given at substantially less-frequent treatment intervals (up to
Q16W), while still achieving comparable visual (BCVA) and anatomic (OCT)
outcomes. Based on the totality of evidence from the Phase I and Phase II
studies, and taking into account evidence from the murine and non-human primate
preclinical and toxicology models, it is anticipated that the additional
anti*Ang-2 mechanism of action of the faricimab molecule will not negatively
impact the safety profile compared with IVT anti-VEGF monotherapy, while
less-frequent dosing may offer a more favorable benefit*risk profile.
Taken together, data from nonclinical, Phase I and Phase II studies, as well as
the clear unmet need for less-frequent dosing in nAMD, support the positive
benefit*risk assessment for the initiation of this Phase III study to assess
the efficacy, safety, durability, and pharmacokinetics of faricimab
administered up to Q16W to patients with nAMD.
Beneluxlaan 2a
Woerden 3446 GR
NL
Beneluxlaan 2a
Woerden 3446 GR
NL
Listed location countries
Age
Inclusion criteria
- Age ><= 50 years , - Ability to comply with the study protocol, - For
women of childbearing potential: agreement to remain abstinent or use
acceptable contraceptive methods during the treatment period and for at least 3
months after the final dose of study treatment, - Treatment-naïve choroidal
neovascularization (CNV) secondary to AMD (nAMD) in the study eye, - BCVA of
20/32 to 20/320 (letter score of 78 to 24) in the study eye at the initiation
of treatment
Exclusion criteria
- Uncontrolled blood pressure, - Pregnancy or breastfeeding, or intention
to become pregnant during the study, - CNV due to causes other than AMD in the
study eye, - Any history of macular pathology unrelated to AMD affecting
vision or contributing to the presence of intraretinal or subretinal fluid in
the study eye, - Presence at screening of central serous chorioretinopathy in
the study eye, - Retinal pigment epithelial tear involving the macula on Day 1
in the study eye, - On FFA/ Color fundus photograph: , o Subretinal hemorrhage
of > 50% of the total lesion area and/or that involves the fovea, o Fibrosis or
atrophy of > 50% of the total lesion area and/or that involves the fovea, -
Any concurrent intraocular condition in the study eye that, in the opinion of
the investigator, could either reduce the potential for visual improvement or
require medical or surgical intervention during the study , - Current vitreous
hemorrhage on Day 1 in the study eye, - Uncontrolled glaucoma in the study
eye, - Spherical equivalent of refractive error demonstrating more than 8
diopters of myopia in the study eye, - Any prior or concomitant treatment for
CNV or vitreomacular-interface abnormalities in the study eye, - Any cataract
surgery or treatment for complications of cataract surgery with steroids or YAG
laser capsulotomy in the study eye within 3 months prior to Day 1, - Any other
intraocular surgery in the study eye, - Prior periocular pharmacological or
IVT treatment for other retinal diseases in the study eye, - Prior IVT
administration of faricimab in either eye, - Active ocular inflammation or
suspected or active ocular or periocular infection in either eye
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 | EUCTR2018-002152-32-NL |
| ClinicalTrials.gov | NCT03823287 |
| CCMO | NL68873.056.19 |