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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03622593




Registration number
NCT03622593
Ethics application status
Date submitted
1/08/2018
Date registered
9/08/2018
Date last updated
11/06/2020

Titles & IDs
Public title
A Study to Evaluate the Efficacy and Safety of Faricimab (RO6867461) in Participants With Diabetic Macular Edema
Scientific title
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)
Secondary ID [1] 0 0
2017-005105-12
Secondary ID [2] 0 0
GR40398
Universal Trial Number (UTN)
Trial acronym
RHINE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diabetic Macular Edema 0 0
Condition category
Condition code
Eye 0 0 0 0
Diseases / disorders of the eye
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Aflibercept
Treatment: Drugs - Faricimab
Treatment: Drugs - Sham Procedure

Experimental: A: Faricimab Q8W -

Experimental: B: Faricimab As Specified in Protocol -

Active Comparator: C: Aflibercept Q8W -


Treatment: Drugs: Aflibercept
Aflibercept will be administered by intravitreal (IVT) injection into the study eye once every 8 weeks (Q8W).

Treatment: Drugs: Faricimab
Faricimab will be administered by IVT injection into the study eye either once every 8 weeks (Q8W) in arm A or as specified in the protocol in arm B.

Treatment: Drugs: Sham Procedure
The sham is a procedure that mimics an IVT injection and involves the blunt end of an empty syringe (without a needle) being pressed against the anesthetized eye. It will be administered to participants in all three treatments arms at applicable visits to maintain masking among treatment arms.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Average Change From Baseline in Best-Corrected Visual Acuity (BCVA) at 1 Year - As measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters.
Timepoint [1] 0 0
Baseline (Day 1) and 1 year
Secondary outcome [1] 0 0
Percentage of Participants with a =2-Step Diabetic Retinopathy Severity (DRS) Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale (DRSS) at 1 Year
Timepoint [1] 0 0
Baseline and 1 year
Secondary outcome [2] 0 0
Change From Baseline in BCVA Over Time
Timepoint [2] 0 0
From Baseline up to 2 years
Secondary outcome [3] 0 0
Percentage of Participants Gaining =15 Letters in BCVA From Baseline Over Time
Timepoint [3] 0 0
From Baseline up to 2 years
Secondary outcome [4] 0 0
Percentage of Participants Gaining =10 Letters in BCVA From Baseline Over Time
Timepoint [4] 0 0
From Baseline up to 2 years
Secondary outcome [5] 0 0
Percentage of Participants Gaining =5 Letters in BCVA From Baseline Over Time
Timepoint [5] 0 0
From Baseline up to 2 years
Secondary outcome [6] 0 0
Percentage of Participants Gaining =0 Letters in BCVA From Baseline Over Time
Timepoint [6] 0 0
From Baseline up to 2 years
Secondary outcome [7] 0 0
Percentage of Participants Avoiding a Loss of =15 Letters in BCVA From Baseline Over Time
Timepoint [7] 0 0
From Baseline up to 2 years
Secondary outcome [8] 0 0
Percentage of Participants Avoiding a Loss of =10 Letters in BCVA From Baseline Over Time
Timepoint [8] 0 0
From Baseline up to 2 years
Secondary outcome [9] 0 0
Percentage of Participants Avoiding a Loss of =5 Letters in BCVA From Baseline Over Time
Timepoint [9] 0 0
From Baseline up to 2 years
Secondary outcome [10] 0 0
Percentage of Participants Avoiding a Loss of >0 Letters in BCVA From Baseline Over Time
Timepoint [10] 0 0
From Baseline up to 2 years
Secondary outcome [11] 0 0
Percentage of Participants Gaining =15 Letters or Achieving BCVA of =84 Letters Over Time
Timepoint [11] 0 0
Up to 2 years
Secondary outcome [12] 0 0
Percentage of Participants with BCVA Snellen Equivalent of 20/40 or Better Over Time
Timepoint [12] 0 0
Up to 2 years
Secondary outcome [13] 0 0
Percentage of Participants with BCVA Snellen Equivalent of 20/200 or Worse Over Time
Timepoint [13] 0 0
Up to 2 years
Secondary outcome [14] 0 0
Percentage of Participants with a =2-Step DRS Improvement From Baseline on the ETDRS DRSS Over Time
Timepoint [14] 0 0
From Baseline up to 2 years
Secondary outcome [15] 0 0
Percentage of Participants with a =3-Step DRS Improvement From Baseline on the ETDRS DRSS Over Time
Timepoint [15] 0 0
From Baseline up to 2 years
Secondary outcome [16] 0 0
Percentage of Participants Who Develop New Proliferative Diabetic Retinopathy Over Time
Timepoint [16] 0 0
Up to 2 years
Secondary outcome [17] 0 0
Percentage of Participants in the Faricimab As Specified in Protocol Arm on a Q4W, Q8W, Q12W, or Q16W Treatment Interval at 1 Year
Timepoint [17] 0 0
1 year
Secondary outcome [18] 0 0
Percentage of Participants in the Faricimab As Specified in Protocol Arm on a Q4W, Q8W, Q12W, or Q16W Treatment Interval at 2 Years
Timepoint [18] 0 0
2 years
Secondary outcome [19] 0 0
Change From Baseline in Central Subfield Thickness Over Time
Timepoint [19] 0 0
From Baseline up to 2 years
Secondary outcome [20] 0 0
Change From Baseline in Central Subfield Thickness at 1 Year
Timepoint [20] 0 0
Baseline and 1 year
Secondary outcome [21] 0 0
Percentage of Participants with Absence of DME Over Time
Timepoint [21] 0 0
Up to 2 years
Secondary outcome [22] 0 0
Percentage of Participants with Absence of Intraretinal Fluid Over Time
Timepoint [22] 0 0
Up to 2 years
Secondary outcome [23] 0 0
Percentage of Participants with Absence of Subretinal Fluid Over Time
Timepoint [23] 0 0
Up to 2 years
Secondary outcome [24] 0 0
Percentage of Participants with Absence of Intraretinal Fluid and Subretinal Fluid Over Time
Timepoint [24] 0 0
Up to 2 years
Secondary outcome [25] 0 0
Change From Baseline in National Eye Institute Visual Functioning Questionnaire-25 (NEI VFQ-25) Composite Score Over Time
Timepoint [25] 0 0
From Baseline up to 2 years
Secondary outcome [26] 0 0
Percentage of Participants with At Least One Ocular Adverse Event
Timepoint [26] 0 0
Up to 2 years
Secondary outcome [27] 0 0
Percentage of Participants with At Least One Non-Ocular Adverse Event
Timepoint [27] 0 0
Up to 2 years
Secondary outcome [28] 0 0
Plasma Concentration of Faricimab Over Time
Timepoint [28] 0 0
Pre-dose on Day 1; Weeks 4, 28, 52, 76, and 100; and at Early Termination Visit (up to 2 years)
Secondary outcome [29] 0 0
Percentage of Participants with Presence of Anti-Drug Antibodies
Timepoint [29] 0 0
Pre-dose on Day 1; Weeks 4, 28, 52, 76, and 100; and at Early Termination Visit (up to 2 years)

Eligibility
Key inclusion criteria
- Documented diagnosis of diabetes mellitus (Type 1 or Type 2)

- Hemoglobin A1c (HbA1c) of less than or equal to (=)10% within 2 months prior to Day 1

- Macular thickening secondary to diabetic macular edema (DME) involving the center of
the fovea

- Decreased visual acuity attributable primarily to DME

- Ability and willingness to undertake all scheduled visits and assessments

- For women of childbearing potential: agreement to remain abstinent or use acceptable
contraceptive methods that result in a failure rate of <1% per year during the
treatment period and for at least 3 months after the final dose of study treatment
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Currently untreated diabetes mellitus or previously untreated patients who initiated
oral or injectable anti-diabetic medication within 3 months prior to Day 1

- Uncontrolled blood pressure, defined as a systolic value greater than (>)180
millimeters of mercury (mmHg) and/or a diastolic value >100 mmHg while a patient is at
rest

- Currently pregnant or breastfeeding, or intend to become pregnant during the study

- Treatment with panretinal photocoagulation or macular laser within 3 months prior to
Day 1 to the study eye

- Any intraocular or periocular corticosteroid treatment within 6 months prior to Day 1
to the study eye

- Prior administration of IVT faricimab in either eye

- Active intraocular or periocular infection or active intraocular inflammation in the
study eye

- 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

- 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

- Other protocol-specified inclusion/exclusion criteria may apply

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC,WA
Recruitment hospital [1] 0 0
Strathfield Retina Clinic - Strathfield
Recruitment hospital [2] 0 0
Sydney Eye Hospital - Sydney
Recruitment hospital [3] 0 0
Sydney Retina Clinic and Day Surgery - Sydney
Recruitment hospital [4] 0 0
Sydney West Retina - Westmead
Recruitment hospital [5] 0 0
Centre For Eye Research Australia - East Melbourne
Recruitment hospital [6] 0 0
Retina Specialists Victoria - Rowville
Recruitment hospital [7] 0 0
The Lions Eye Institute - Nedlands
Recruitment postcode(s) [1] 0 0
2135 - Strathfield
Recruitment postcode(s) [2] 0 0
2000 - Sydney
Recruitment postcode(s) [3] 0 0
2145 - Westmead
Recruitment postcode(s) [4] 0 0
3002 - East Melbourne
Recruitment postcode(s) [5] 0 0
3178 - Rowville
Recruitment postcode(s) [6] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
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United States of America
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Arkansas
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United States of America
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California
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United States of America
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Colorado
Country [5] 0 0
United States of America
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Connecticut
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Florida
Country [7] 0 0
United States of America
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Georgia
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United States of America
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Illinois
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United States of America
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Maryland
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Massachusetts
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Michigan
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Nevada
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New Jersey
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New York
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Ohio
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South Carolina
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Tennessee
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Texas
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Virginia
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United States of America
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Washington
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Argentina
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Buenos Aires
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Argentina
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Caba
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Argentina
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Capital Federal
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Argentina
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Mendoza
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Argentina
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Rosario
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Brazil
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GO
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Brazil
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RS
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Brazil
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China
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China
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China
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China
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China
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Wuxi
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Czechia
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Hradec Králové
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Ostrava
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Prague
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Aalborg
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Seoul
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Valencia
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Spain
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Valladolid
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Binningen
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Taipei
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Taoyuan
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Taiwan
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Zhongzheng Dist.
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Bangkok
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Thailand
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ChiangMai
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Turkey
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Ankara
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Turkey
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Istanbul
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Turkey
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Kocaeli
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United Kingdom
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Barnet
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Bradford
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Bristol
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Canterbury
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Frimley
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Gloucestershire
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Leeds
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Liverpool
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London
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Manchester
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Middx
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Newcastle upon Tyne
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Norfolk
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Southampton
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Sunderland

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This study will evaluate the efficacy, safety, and pharmacokinetics of faricimab administered
at 8-week intervals or as specified in the protocol following treatment initiation, compared
with aflibercept once every 8 weeks (Q8W), in participants with diabetic macular edema (DME).

The global enrollment phase has closed, but participants are still being recruited only at
sites in China.
Trial website
https://clinicaltrials.gov/show/NCT03622593
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03622593