Clinical Trials List
Protocol NumberGR40398
NCT Number(ClinicalTrials.gov Identfier)NCT03622593
Completed
2018-11-01 - 2023-12-31
Phase III
Terminated3
ICD-10 E11.311
Type 2 diabetes mellitus with unspecified diabetic retinopathy with macular edema
A Phase III, Multicenter, Randomized, Double-Masked, Active Comparator-Controlled Study to Evaluate the Efficacy and Safety of Faricimab (RO6867461) in Patients With Diabetic Macular Edema (RHINE)
-
Trial Applicant
-
Sponsor
Hoffmann-La Roche
-
Trial scale
Multi-Regional Multi-Center
-
Update
2026/02/01
Investigators and Locations
Co-Principal Investigator
- An-Fei Li Division of Ophthalmology
- De-Kuang Hwang Division of Ophthalmology
- 林泰祺 Division of Ophthalmology
- 周昱百 Division of Ophthalmology
- 黃怡銘 Division of Ophthalmology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- 劉珍吟 Division of Ophthalmology
- 陳冠任 Division of Ophthalmology
- Yih-Shiou Hwang Division of Ophthalmology
- Wei-Chi WU Division of Ophthalmology
- 陳彥伯 Division of Ophthalmology
- 范遠耀 Division of Ophthalmology
- 陳墩祿 Division of Ophthalmology
- 周宏達 Division of Ophthalmology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- CHUNG-MAY YANG Division of Ophthalmology
- Ta-Ching Chen Division of Ophthalmology
- 謝易庭 Division of Ophthalmology
- TZYY-CHANG HO Division of Ophthalmology
- 葉伯廷 Division of Ophthalmology
- TSO-TING LAI Division of Ophthalmology
The Actual Total Number of Participants Enrolled
0 Terminated
Audit
None
Condition/Disease
Diabetic Macular Edema
Objectives
This study will evaluate the efficacy, safety, and pharmacokinetics of RO6867461 when
dosed Q8W and with a PTI regimen compared with aflibercept (Eylea®) monotherapy in patients with DME.
Test Drug
FARICIMAB (RO6867461)
Active Ingredient
Aflibercept
FARICIMAB (RO6867461)
FARICIMAB (RO6867461)
Dosage Form
IVT
IVT
IVT
Dosage
6 mg/ 0.05 ml
2 mg/ 0.05 ml
2 mg/ 0.05 ml
Endpoints
Change from baseline in BCVA (as measured on the ETDRS chart at a starting distance of 4 meters) at 1 year
Proportion of patients with a >= 2 step DRS improvement from baseline on the ETDRS DRSS at Week 52
Change from baseline in BCVA (as measured on the ETDRS chart at a starting distance of 4 meters) over time
Proportion of patients gaining >=15、>=10、>=5 or >= 0 letters in BCVA from baseline over time
Proportion of patients avoiding a loss of =15、>=10、>=5 or >0 letters in BCVA from baseline over time
Incidence and severity of ocular adverse events
Incidence and severity of non-ocular adverse events
Proportion of patients with a >= 2 step DRS improvement from baseline on the ETDRS DRSS at Week 52
Change from baseline in BCVA (as measured on the ETDRS chart at a starting distance of 4 meters) over time
Proportion of patients gaining >=15、>=10、>=5 or >= 0 letters in BCVA from baseline over time
Proportion of patients avoiding a loss of =15、>=10、>=5 or >0 letters in BCVA from baseline over time
Incidence and severity of ocular adverse events
Incidence and severity of non-ocular adverse events
Inclution Criteria
General Inclusion Criteria
Patients must meet the following general inclusion criteria for study entry:
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.
Age 18 years
Documented diagnosis of diabetes mellitus (Type 1 or Type 2), as defined by the
American Diabetes Association or per WHO criteria and
– Current regular use of insulin for the treatment of diabetes
and/or
– Current regular use of oral anti-hyperglycemic agents for the treatment of
diabetes
HbA1c of 10% within 2 months prior to the Day 1 visit date
Ability and willingness to undertake all scheduled visits and assessments
For women of childbearing potential: agreement to remain abstinent (refrain from
heterosexual intercourse) or use acceptable contraceptive methods during the
treatment period and for at least 3 months after the final dose of study treatment
A woman is considered to be of childbearing potential if she is postmenarcheal,
has not reached a postmenopausal state (12 continuous months of amenorrhea
with no identified cause other than menopause), and has not undergone surgical
sterilization (removal of ovaries and/or uterus). The definition of childbearing
potential may be adapted for alignment with local guidelines or requirements.
The following are acceptable contraceptive methods: bilateral tubal ligation,
male sterilization; hormonal contraceptives that inhibit ovulation, hormonereleasing intrauterine devices; copper intrauterine devices; male or female
condom with or without spermicide; and cap, diaphragm, or sponge with
spermicide.
The reliability of sexual abstinence should be evaluated in relation to the duration
of the clinical trial and the preferred and usual lifestyle of the patient. If a patient
is usually not sexually active but becomes active, they, with their partner, must
comply with the contraceptive requirements of the study.
For patients enrolled in the China extension at China FDA-recognized sites:
current residents of mainland China, Hong Kong, or Taiwan
Ocular Inclusion Criteria for Study Eye
Patients must meet the following ocular inclusion criteria for the study eye for entry in
the study:
Macular thickening secondary to DME involving the center of the fovea with CST
325 m, as measured on Spectralis SD-OCT, or 315 m, as measured on Cirrus
SD-OCT or Topcon SD-OCT at screening BCVA of 73 to 25 letters, inclusive (20/40 to 20/320 approximate Snellen equivalent),
using the ETDRS protocol at the initial testing distance of 4 meters (see the BCVA
manual for additional details) on Day 1
Sufficiently clear ocular media and adequate pupillary dilatation to allow acquisition
of good quality CFPs (including ETDRS 7 modified fields or 4 wide-angle fields to
permit grading of DR and assessment of the retina) and other imaging modalities.
Patients must meet the following general inclusion criteria for study entry:
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.
Age 18 years
Documented diagnosis of diabetes mellitus (Type 1 or Type 2), as defined by the
American Diabetes Association or per WHO criteria and
– Current regular use of insulin for the treatment of diabetes
and/or
– Current regular use of oral anti-hyperglycemic agents for the treatment of
diabetes
HbA1c of 10% within 2 months prior to the Day 1 visit date
Ability and willingness to undertake all scheduled visits and assessments
For women of childbearing potential: agreement to remain abstinent (refrain from
heterosexual intercourse) or use acceptable contraceptive methods during the
treatment period and for at least 3 months after the final dose of study treatment
A woman is considered to be of childbearing potential if she is postmenarcheal,
has not reached a postmenopausal state (12 continuous months of amenorrhea
with no identified cause other than menopause), and has not undergone surgical
sterilization (removal of ovaries and/or uterus). The definition of childbearing
potential may be adapted for alignment with local guidelines or requirements.
The following are acceptable contraceptive methods: bilateral tubal ligation,
male sterilization; hormonal contraceptives that inhibit ovulation, hormonereleasing intrauterine devices; copper intrauterine devices; male or female
condom with or without spermicide; and cap, diaphragm, or sponge with
spermicide.
The reliability of sexual abstinence should be evaluated in relation to the duration
of the clinical trial and the preferred and usual lifestyle of the patient. If a patient
is usually not sexually active but becomes active, they, with their partner, must
comply with the contraceptive requirements of the study.
For patients enrolled in the China extension at China FDA-recognized sites:
current residents of mainland China, Hong Kong, or Taiwan
Ocular Inclusion Criteria for Study Eye
Patients must meet the following ocular inclusion criteria for the study eye for entry in
the study:
Macular thickening secondary to DME involving the center of the fovea with CST
325 m, as measured on Spectralis SD-OCT, or 315 m, as measured on Cirrus
SD-OCT or Topcon SD-OCT at screening BCVA of 73 to 25 letters, inclusive (20/40 to 20/320 approximate Snellen equivalent),
using the ETDRS protocol at the initial testing distance of 4 meters (see the BCVA
manual for additional details) on Day 1
Sufficiently clear ocular media and adequate pupillary dilatation to allow acquisition
of good quality CFPs (including ETDRS 7 modified fields or 4 wide-angle fields to
permit grading of DR and assessment of the retina) and other imaging modalities.
Exclusion Criteria
General Exclusion Criteria
Patients who meet any of the following general exclusion criteria will be excluded from
study entry:
Currently untreated diabetes mellitus or previously untreated patients who initiated
oral anti-diabetic medication or insulin within 3 months prior to Day 1
History of allergy or hypersensitivity to active drug aflibercept and any of its
excipients, fluorescein, or any study treatmentrelated mandatory ingredients
(e.g., disinfectants, anesthetics, etc.; see the pharmacy manual for additional
details) 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 RO6867461 or to aflibercept
injections, study treatment procedure, dilating drops, or any of the anesthetic and
antimicrobial drops used by a patient during the study
Active cancer within the 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 for 12 months
Systemic treatment for suspected or active systemic infection
Ongoing use of prophylactic antibiotic therapy may be acceptable but has to be
discussed with the Medical Monitor.
Renal failure requiring renal transplant, hemodialysis, or peritoneal dialysis within
6 months prior to Day 1 or anticipated to require hemodialysis or peritoneal dialysis
at any time during the study
History of other disease, other non-diabetic metabolic dysfunction, physical
examination finding, or clinical laboratory finding giving reasonable suspicion of a
condition that contraindicates the use of the RO6867461 or aflibercept or that might
affect interpretation of the results of the study or renders the patient at high risk for
treatment complications in the opinion of the investigator
Uncontrolled blood pressure (defined as systolic 180 mmHg and/or diastolic
100 mmHg while a patient is at rest)
If a patient’s initial reading exceeds these values, a second reading may be
obtained later the same day or on another day during the screening period. If the patient’s blood pressure is controlled by antihypertensive medication, the patient
should be taking the same medication continuously for at least 30 days prior to
Day 1.
Cerebral vascular accident or myocardial infarction within 6 months prior to Day 1
Pregnancy or breastfeeding, or intention to become pregnant during the study
Women of childbearing potential must have a negative urine pregnancy test
result within 28 days prior to initiation of study treatment. If the urine
pregnancy test is positive, it must be confirmed by a serum pregnancy test.
Participation in an investigational trial that involves treatment with any drug or
device (with the exception of vitamins and minerals) within 3 months prior to Day 1
Administration of systemic pro-angiogenic treatments, such as VEGF-based
therapies for the peripheral or coronary ischemia (e.g., limb ischemia or myocardial
infarction) within 3 months or 5 half-lives prior to Day 1
Inability to comply with study or follow-up procedures
Requirement for continuous use of any medications and treatments indicated in
Section 4.4.2, Prohibited Therapy
Ocular Exclusion Criteria for Study Eye
Patients who meet any of the following exclusion criteria for the study eye will be
excluded from study entry:
High-risk PDR in the study eye, using any of the following established criteria for
high-risk PDR:
– Any vitreous or pre-retinal hemorrhage
– Neovascularization elsewhere 1/2 disc area within an area equivalent to the
mydriatic ETDRS 7 fields on clinical examination or on CFPs
– Neovascularization at disc 1/3 disc area on clinical examination
Tractional retinal detachment, pre-retinal fibrosis, or epiretinal membrane involving
the fovea or disrupting the macular architecture in the study eye
Active rubeosis
Uncontrolled glaucoma
History of retinal detachment or macular hole (Stage 3 or 4)
Aphakia or implantation of anterior chamber intraocular lens
IVT anti-VEGF treatment within 3 months prior to Day 1 (applicable to patients
whose study eyes were previously treated with IVT anti-VEGF agents) or any IVT
anti-VEGF agents to study eye prior to Day 1 (applicable for patients who are
treatment naive)
Treatment with panretinal photocoagulation (PRP) within 3 months prior to Day 1
Macular (focal or grid) laser within 3 months prior to Day 1
Any cataract surgery or treatment for complications of cataract surgery with steroids
or YAG (yttrium-aluminum-garnet) laser capsulotomy within 3 months prior to Day 1
Any other intraocular surgery (e.g., corneal transplantation, glaucoma filtration, pars
plana vitrectomy, corneal transplant, or radiotherapy)
Any IVT or periocular (subtenon) corticosteroid treatment within 6 months prior to
Day 1
Any use of medicated intraocular implants, including Ozurdex®
, within 6 months of
Day 1
Any use of Iluvien®
implants at any time prior to Day 1
Treatment for other retinal diseases that can lead to macular edema
Ocular Exclusion Criteria for Fellow Eye (NonStudy Eye)
Patients who meet the following exclusion criterion for the fellow eye (nonstudy eye)
will be excluded from study entry:
Non-functioning nonstudy eye, defined as either:
– BCVA of hand motion or worse
– No physical presence of nonstudy eye (i.e., monocular)
Exclusion Criteria for Both Eyes
Patients who meet the following exclusion criterion for either eye will be excluded from
study entry:
Prior administration of IVT RO6867461 in either eye
Any history of idiopathic or immune-mediated uveitis in either eye
Active ocular inflammation or suspected or active ocular or periocular infection in
either eye on Day 1
Concurrent Ocular Conditions Exclusion Criteria
Patients who meet the following exclusion criteria related to concurrent ocular conditions
will be excluded from study entry:
Any current or history of ocular disease other than DME that may confound
assessment of the macula or affect central vision in the study eye (e.g., choroidal
neovascularization, age-related macular degeneration, retinal vein occlusion, uveitis,
angioid streaks, histoplasmosis, active or inactive cytomegalovirus, pathological
myopia, retinal detachment, macular traction, macular hole, and other)
Any current ocular condition which, in the opinion of the investigator, is currently
causing or could be expected to contribute to irreversible vision loss due to a cause
other than DME in the study eye (e.g., foveal atrophy, foveal fibrosis, pigment
abnormalities, dense subfoveal hard exudates, or other non-retinal conditions)
Patients who meet any of the following general exclusion criteria will be excluded from
study entry:
Currently untreated diabetes mellitus or previously untreated patients who initiated
oral anti-diabetic medication or insulin within 3 months prior to Day 1
History of allergy or hypersensitivity to active drug aflibercept and any of its
excipients, fluorescein, or any study treatmentrelated mandatory ingredients
(e.g., disinfectants, anesthetics, etc.; see the pharmacy manual for additional
details) 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 RO6867461 or to aflibercept
injections, study treatment procedure, dilating drops, or any of the anesthetic and
antimicrobial drops used by a patient during the study
Active cancer within the 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 for 12 months
Systemic treatment for suspected or active systemic infection
Ongoing use of prophylactic antibiotic therapy may be acceptable but has to be
discussed with the Medical Monitor.
Renal failure requiring renal transplant, hemodialysis, or peritoneal dialysis within
6 months prior to Day 1 or anticipated to require hemodialysis or peritoneal dialysis
at any time during the study
History of other disease, other non-diabetic metabolic dysfunction, physical
examination finding, or clinical laboratory finding giving reasonable suspicion of a
condition that contraindicates the use of the RO6867461 or aflibercept or that might
affect interpretation of the results of the study or renders the patient at high risk for
treatment complications in the opinion of the investigator
Uncontrolled blood pressure (defined as systolic 180 mmHg and/or diastolic
100 mmHg while a patient is at rest)
If a patient’s initial reading exceeds these values, a second reading may be
obtained later the same day or on another day during the screening period. If the patient’s blood pressure is controlled by antihypertensive medication, the patient
should be taking the same medication continuously for at least 30 days prior to
Day 1.
Cerebral vascular accident or myocardial infarction within 6 months prior to Day 1
Pregnancy or breastfeeding, or intention to become pregnant during the study
Women of childbearing potential must have a negative urine pregnancy test
result within 28 days prior to initiation of study treatment. If the urine
pregnancy test is positive, it must be confirmed by a serum pregnancy test.
Participation in an investigational trial that involves treatment with any drug or
device (with the exception of vitamins and minerals) within 3 months prior to Day 1
Administration of systemic pro-angiogenic treatments, such as VEGF-based
therapies for the peripheral or coronary ischemia (e.g., limb ischemia or myocardial
infarction) within 3 months or 5 half-lives prior to Day 1
Inability to comply with study or follow-up procedures
Requirement for continuous use of any medications and treatments indicated in
Section 4.4.2, Prohibited Therapy
Ocular Exclusion Criteria for Study Eye
Patients who meet any of the following exclusion criteria for the study eye will be
excluded from study entry:
High-risk PDR in the study eye, using any of the following established criteria for
high-risk PDR:
– Any vitreous or pre-retinal hemorrhage
– Neovascularization elsewhere 1/2 disc area within an area equivalent to the
mydriatic ETDRS 7 fields on clinical examination or on CFPs
– Neovascularization at disc 1/3 disc area on clinical examination
Tractional retinal detachment, pre-retinal fibrosis, or epiretinal membrane involving
the fovea or disrupting the macular architecture in the study eye
Active rubeosis
Uncontrolled glaucoma
History of retinal detachment or macular hole (Stage 3 or 4)
Aphakia or implantation of anterior chamber intraocular lens
IVT anti-VEGF treatment within 3 months prior to Day 1 (applicable to patients
whose study eyes were previously treated with IVT anti-VEGF agents) or any IVT
anti-VEGF agents to study eye prior to Day 1 (applicable for patients who are
treatment naive)
Treatment with panretinal photocoagulation (PRP) within 3 months prior to Day 1
Macular (focal or grid) laser within 3 months prior to Day 1
Any cataract surgery or treatment for complications of cataract surgery with steroids
or YAG (yttrium-aluminum-garnet) laser capsulotomy within 3 months prior to Day 1
Any other intraocular surgery (e.g., corneal transplantation, glaucoma filtration, pars
plana vitrectomy, corneal transplant, or radiotherapy)
Any IVT or periocular (subtenon) corticosteroid treatment within 6 months prior to
Day 1
Any use of medicated intraocular implants, including Ozurdex®
, within 6 months of
Day 1
Any use of Iluvien®
implants at any time prior to Day 1
Treatment for other retinal diseases that can lead to macular edema
Ocular Exclusion Criteria for Fellow Eye (NonStudy Eye)
Patients who meet the following exclusion criterion for the fellow eye (nonstudy eye)
will be excluded from study entry:
Non-functioning nonstudy eye, defined as either:
– BCVA of hand motion or worse
– No physical presence of nonstudy eye (i.e., monocular)
Exclusion Criteria for Both Eyes
Patients who meet the following exclusion criterion for either eye will be excluded from
study entry:
Prior administration of IVT RO6867461 in either eye
Any history of idiopathic or immune-mediated uveitis in either eye
Active ocular inflammation or suspected or active ocular or periocular infection in
either eye on Day 1
Concurrent Ocular Conditions Exclusion Criteria
Patients who meet the following exclusion criteria related to concurrent ocular conditions
will be excluded from study entry:
Any current or history of ocular disease other than DME that may confound
assessment of the macula or affect central vision in the study eye (e.g., choroidal
neovascularization, age-related macular degeneration, retinal vein occlusion, uveitis,
angioid streaks, histoplasmosis, active or inactive cytomegalovirus, pathological
myopia, retinal detachment, macular traction, macular hole, and other)
Any current ocular condition which, in the opinion of the investigator, is currently
causing or could be expected to contribute to irreversible vision loss due to a cause
other than DME in the study eye (e.g., foveal atrophy, foveal fibrosis, pigment
abnormalities, dense subfoveal hard exudates, or other non-retinal conditions)
The Estimated Number of Participants
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Taiwan
24 participants
-
Global
900 participants
