Visual Impairment Due to Choroidal Neovascularization (CNV) Secondary to Pathologic Myopia (PM)Phase 3BrillianceNCT01922102

Efficacy and Safety of Ranibizumab 0.5 vs Verteporfin PDT in Patients With Visual Impairment Due to Choroidal Neovascularization Secondary to Pathologic Myopia

A Phase 3 study testing Ranibizumab 0.5mg, Ranibizumab 0.5 mg and Verteporfin PDT in people with Visual Impairment Due to Choroidal Neovascularization (CNV) Secondary to Pathologic Myopia (PM), run by Novartis Pharmaceuticals at 47 sites in 6 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This study was designed to evaluate the efficacy and safety of two different dosing regimens of 0.5 mg ranibizumab given as intravitreal injection in comparison to verteporfin PDT in patients with visual impairment due to choroidal neovascularization secondary to pathologic myopia (PM) Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Visual Impairment Due to Choroidal Neovascularization (CNV) Secondary to Pathologic Myopia (PM)
What is being tested?: Ranibizumab 0.5mg, Ranibizumab 0.5 mg and Verteporfin PDT
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 457 participants
Where: 47 sitesin 6 countries
Study dates: 11 Sep 2013to 14 Sep 2016
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Visual impairment due to CNV secondary to PM.
Best corrected visual acuity in the study eye > 24 and < 78 ETDRS letters.
High myopia (> -6D),
anterio-posterior elongation > 26 mm; posterior changes compatible with the pathologic myopia.
Either CNV locations in the study eye: subfoveal, juxtafoveal, extrafoveal.

Who cannot join

Some preexisting eye disorders or systemic diseases;-Blood pressure > 150/90 mmHg
Prior focal/grid laser to the macular area -History of treatment with any anti-VEGF or verteporfin PDT in the study eye
Intravitreal treatment with corticosteroids or intraocular surgery within last 3 months in the study eye

Trial locations and contacts

47 sites in 6 countries.

Country

City, postcode or hospital

47 sites in 6 countries

China27 sites

Novartis Investigative Site
Beijing, Beijing Municipality, 100191
Novartis Investigative Site
Beijing, Beijing Municipality, 100730
Novartis Investigative Site
Beijing, 100034
Novartis Investigative Site
Beijing, 100176
Novartis Investigative Site
Beijing, 100730
Novartis Investigative Site
Changsha, Hunan, 410008
Novartis Investigative Site
Changsha, Hunan, 410011
Novartis Investigative Site
Chengdu, Sichuan, 610041
Novartis Investigative Site
Chongqing, Chongqing Municipality, 400042
Novartis Investigative Site
Chongqing, 400038
Novartis Investigative Site
Hangzhou, Zhejiang, 310009
Novartis Investigative Site
Harbin, Heilongjiang, 150001
Novartis Investigative Site
Nanchang, Jiangxi, 330006
Novartis Investigative Site
Nanjing, Jiangsu, 210006
Novartis Investigative Site
Nanjing, Jiangsu, 210029
Novartis Investigative Site
Qingdao, Shandong, 266011
Novartis Investigative Site
Shanghai, 200080
Novartis Investigative Site
Shanghai, 200092
Novartis Investigative Site
Shanghai
Novartis Investigative Site
Shantou, Guangdong, 515041
Novartis Investigative Site
Tianjin, Tianjin Municipality, 300020
Novartis Investigative Site
Tianjin, Tianjin Municipality, 300070
Novartis Investigative Site
Wenzhou, Zhejiang, 325027
Novartis Investigative Site
Wuhan, Hubei, 430060
Novartis Investigative Site
Wuhan, Hubei, 430070
Novartis Investigative Site
Wuxi, Jiangsu, 214023
Novartis Investigative Site
Xi’an, Shanxi, 710032

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India10 sites

Novartis Investigative Site
Angamaly, 683572
Novartis Investigative Site
Bangalore, Karnataka, 560 010
Novartis Investigative Site
Bhubaneswar, Odisha, 751024
Novartis Investigative Site
Chandīgarh, Haryana, 160 030
Novartis Investigative Site
Chennai, Tamil Nadu, 600 015
Novartis Investigative Site
Chennai, Tamil Nadu, 600006
Novartis Investigative Site
Coimbatore, Tamil Nadu, 641 014
Novartis Investigative Site
Hyderabad, Telangana, 500 034
Novartis Investigative Site
New Delhi, 110029
Novartis Investigative Site
Vanchiyoor, Kerala, 695035

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Thailand4 sites

Novartis Investigative Site
Bangkok, 10700
Novartis Investigative Site
Chiang Mai, 50200
Novartis Investigative Site
Khon Kaen, THA, 40002
Novartis Investigative Site
Nakornphathom, 73210

Other trials in Thailand

South Korea3 sites

Novartis Investigative Site
Pusan, 614 735
Novartis Investigative Site
Seoul, 02841
Novartis Investigative Site
Seoul, 03722

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Philippines2 sites

Novartis Investigative Site
Manila, National Capital Region, 1000
Novartis Investigative Site
Manila, National Capital Region, 1008

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Hong Kong1 site

Novartis Investigative Site
Hong Kong

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About this study

Official title: A 12-month, Phase III, Randomized, Double-masked, Multicenter, Active-controlled Study to Evaluate the Efficacy and Safety of Two Individualized Regimens of 0.5mg Ranibizumab vs. Verteporfin PDT in Patients With Visual Impairment Due to Choroidal Neovascularization Secondary to Pathologic Myopia

Read the detailed description

This was a phase III, multi-center, randomized, double-masked, active-controlled study comparing 0.5 mg ranibizumab vs. vPDT therapy. The study included 15 scheduled visits over 12 months, and there were to be two additional visits (2a, 3a) for subset of patients in whom PK analysis were performed.

There were 3 periods in this study: Screening period-from Day -14 to Baseline; Treatment period-from Baseline to Month 11; Follow-up period-from Month 11 to Month 12 Patients entered the 11 months Treatment period at Visit 2 (Day 1) if eligibility criteria were met and were randomized in three treatment groups Group I ranibizumab 0.5 mg driven by VA stability criteria or Group II ranibizumab 0.5 mg driven by disease activity criteria or Group III vPDT (randomization ratio of 2:2:1) and received first treatment of either a ranibizumab injection and sham vPDT or sham injection and active vPDT and will return to the clinical center within 7 days to undergo safety assessments as well as assessments of the effect of treatment by the evaluating investigator. The following visits were performed at one month intervals starting at Visit 4 and continuing through Visit 14. At all monthly visits (at/from Month 2 for group I, at/from Month 1 for group II and at/from Month 3 for group III) the decision for treatment were made by the evaluating investigator based on the VA stability criteria and on the disease activity criteria. At Month 3 (visit 6) and at all following monthly visits for all three groups one of the three options can recommended by evaluating investigator: a) ranibizumab 0.5 mg, b) ranibizumab 0.5 mg + vPDT; c) vPDT. The treating investigator were then perform treatment based on randomization and masking requirements.

At each monthly visit, patients had a safety evaluation by the evaluating investigator prior to study treatment, consisting of visual acuity measurements, ophthalmic examinations and evaluation of adverse events and vital signs. Routine hematology, chemistry, and urinalysis profiles were obtained at Visit 6, 9 and 12 (Month 3, 6 and 9). At Month 12 several procedures and assessments were performed which are required at study completion visit.

Conditions: Visual Impairment Due to Choroidal Neovascularization (CNV) Secondary to Pathologic Myopia (PM)
Being tested: Ranibizumab 0.5mg, Ranibizumab 0.5 mg, Verteporfin PDT
Keywords: vision loss,PM,CNV,ranibizumab,verteporfinPDT,Brilliance
Medical subject headings: Choroidal Neovascularization

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Ranibizumab 0.5mgDrug
Also called Lucentis
0.5 mg ranibizumab (intravitreal injections)
Ranibizumab 0.5 mgDrug
Also called Lucentis
0.5 mg ranibizumab (intravitreal injections)
Verteporfin PDTDrug
Also called Visudyne
Verteporfin for intravenous injection delivered by intravenous infusion followed by the light application

Study groups in NCT01922102
Study group	Role	What they receive
Group I	Experimental	0.5 mg ranibizumab driven by visual acuity stability criteria Receives: Drug: Ranibizumab 0.5mg
Group II	Experimental	0.5 mg ranibizumab driven by disease activity criteria Receives: Drug: Ranibizumab 0.5 mg
Group III	Active comparator	verteporfin PDT Receives: Drug: Verteporfin PDT

What is being measured

The primary outcome is the main question the study is designed to answer.

Change From Baseline BCVA to the Average Level of BCVA Over All Monthly Assessments From Month 1 to Month 3
Best corrected visual acuity (BCVA) was tested using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) charts testing protocol. VA measurements were taken in a sitting position at an initial test distance of 4 meters using ETDRS charts. The overall BCVA score was calculated using the BCVA worksheet, which was kept in the source data and the score was recorded in the eCRF.
Measured: From Baseline to Month 3

Secondary outcomes (8)

Change From Baseline BCVA to the Average Level of BCVA Over All Monthly Assessments From Month 1 to Month 6
Best corrected visual acuity (BCVA) was tested using the early treatment diabetic retinopathy study (ETDRS) VA testing protocol. VA measurements were taken in a sitting position at an initial test distance of 4 meters using ETDRS charts. The overall BCVA score was calculated using the BCVA worksheet, which was kept in the source data and the score was recorded in the eCRF.
Between treatment comparison of 0.5 mg ranibizumab intravitreal injections driven by disease activity re-treatment criteria (Group II) versus 0.5 mg ranibizumab intravitreal injections driven by visual acuity stability criteria (Group I) based on the average BCVA change from Baseline to Month 1 through Month 6.
Measured: From Baseline to Month 6
The Average Change in BCVA Score From Baseline to Month 1 Through Month 12
Best corrected visual acuity (BCVA) was tested using the ETDRS VA testing protocol. VA measurements were taken in a sitting position at an initial test distance of 4 meters using ETDRS charts. The overall BCVA score was calculated using the BCVA worksheet, which was kept in the source data and the score was recorded in the eCRF.
Between treatment comparison of 0.5 mg ranibizumab intravitreal injections driven by disease activity re-treatment criteria (Group II) versus 0.5 mg ranibizumab intravitreal injections driven by visual acuity stability criteria (Group I) based on the average BCVA change from Baseline to Month 1 through Month 12
Measured: From Baseline to Month 12
Mean Change From Baseline in Visual Acuity Over Time
Best corrected visual acuity (BCVA) was tested using the ETDRS VA testing protocol. VA measurements were taken in a sitting position at an initial test distance of 4 meters using ETDRS charts. The overall BCVA score was calculated using the BCVA worksheet, which was kept in the source data and the score was recorded in the eCRF.
Measured: Change from baseline at months 3, 6, and 12
Categorized BCVA Changes at Months 3, 6 and 12 Compared With Baseline for the Study Eye
ETDRS VA testing protocol. VA measurements were taken in a sitting position at an initial test distance of 4 meters using ETDRS charts. The overall BCVA score was calculated using the BCVA worksheet, which was kept in the source data and the score was recorded in the eCRF.
Measured: From Baseline to Month 12
Mean Change From Baseline Over Time in Central Sub-field Thickness (CSFT)
Central sub-field thickness (CSFT) is a variable assessed via Optical Coherence Tomography (OCT). OCT was performed prior to any study drug administration to assess presence of intra, subretinal fluid, or increase of CSFT.
Measured: Baseline, Month 3, Month 6, and Month 12
Number of Patients With CNV Leakage (Center Involvement) in the Study Eye at Baseline and Month 12
CNV leakage is assessed via fluorescein angiography (center involvement) category: definite, questionable, absent, can't grade, and missing.
Measured: From Baseline until Month 12
NEI-VFQ-25 - Change From Baseline to Month 3, 6 and 12
The VFQ-25 consists of 25 vision related questions across 11 vision related subscales, including general vision, ocular pain, near activities, distance activities, social function, mental health, role difficulties, dependency, driving, color vision and peripheral vision, and a general health rating. Items are converted to a 0-100 scale on each subscale and for the composite score where higher scores represents better functioning.
Measured: Change from baseline at month 3, 6 and 12
Number of Ranibizumab Injections Received in the Study Eye for the Ranibizumab Groups
To assess treatment pattern with ranibizumab
Measured: From Baseline to Month 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

11 Sep 201314 Sep 2016

First posted14 Aug 2013 (estimated)
Study start11 Sep 2013
Primary completion14 Sep 2016
Study completion14 Sep 2016

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Visual Impairment Due to Choroidal Neovascularization (CNV) Secondary to Pathologic Myopia (PM)Studies of the same condition, open and under way.
More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Investigator, Outcomes assessor
Enrolment: 457 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01922102
Sponsor's protocol ID: CRFB002F2302
Acronym: Brilliance
Status last verified: Mar 2019
First submitted: 12 Aug 2013
Last updated: 24 Jun 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: Undecided: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Study at a glance

From the registry record, last updated by the sponsor on 24 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A 12-month, Phase III, Randomized, Double-masked, Multicenter, Active-controlled Study to Evaluate the Efficacy and Safety of Two Individualized Regimens of 0.5mg Ranibizumab vs. Verteporfin PDT in Patients With Visual Impairment Due to Choroidal Neovascularization Secondary to Pathologic Myopia
ClinicalTrials.gov ID: NCT01922102
Acronym / sponsor ID: Brilliance / CRFB002F2302
Conditions: Visual Impairment Due to Choroidal Neovascularization (CNV) Secondary to Pathologic Myopia (PM)
Keywords: vision loss,PM,CNV,ranibizumab,verteporfinPDT,Brilliance
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 457 participants (actual)
Lead sponsor: Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
Study start: 11 Sep 2013 (actual)
Primary completion: 14 Sep 2016 (actual)
Study completion: 14 Sep 2016 (actual)
First posted: 14 Aug 2013 (estimated)
Results: Posted 24 Jun 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, investigator, outcomes assessor)
Number of arms: 3

Arm	Type	Receives
Group I	Experimental	Drug: Ranibizumab 0.5mg0.5 mg ranibizumab driven by visual acuity stability criteria
Group II	Experimental	Drug: Ranibizumab 0.5 mg0.5 mg ranibizumab driven by disease activity criteria
Group III	Active comparator	Drug: Verteporfin PDTverteporfin PDT

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

Visual impairment due to CNV secondary to PM.
Best corrected visual acuity in the study eye > 24 and < 78 ETDRS letters.
High myopia (> -6D),
anterio-posterior elongation > 26 mm; posterior changes compatible with the pathologic myopia.
Either CNV locations in the study eye: subfoveal, juxtafoveal, extrafoveal.

Key exclusion criteria (3 listed)

Some preexisting eye disorders or systemic diseases;-Blood pressure > 150/90 mmHg
Prior focal/grid laser to the macular area -History of treatment with any anti-VEGF or verteporfin PDT in the study eye
Intravitreal treatment with corticosteroids or intraocular surgery within last 3 months in the study eye

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Ranibizumab 0.5mgAlso: Lucentis0.5 mg ranibizumab (intravitreal injections)	Drug	Group I
Ranibizumab 0.5 mgAlso: Lucentis0.5 mg ranibizumab (intravitreal injections)	Drug	Group II
Verteporfin PDTAlso: VisudyneVerteporfin for intravenous injection delivered by intravenous infusion followed by the light application	Drug	Group III

Primary outcome

Change From Baseline BCVA to the Average Level of BCVA Over All Monthly Assessments From Month 1 to Month 3
Time frame: From Baseline to Month 3
Best corrected visual acuity (BCVA) was tested using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) charts testing protocol. VA measurements were taken in a sitting position at an initial test distance of 4 meters using ETDRS charts. The overall BCVA score was calculated using the BCVA worksheet, which was kept in the source data and the score was recorded in the eCRF.

8 secondary outcomes

Change From Baseline BCVA to the Average Level of BCVA Over All Monthly Assessments From Month 1 to Month 6
Time frame: From Baseline to Month 6
The Average Change in BCVA Score From Baseline to Month 1 Through Month 12
Time frame: From Baseline to Month 12
Mean Change From Baseline in Visual Acuity Over Time
Time frame: Change from baseline at months 3, 6, and 12
Categorized BCVA Changes at Months 3, 6 and 12 Compared With Baseline for the Study Eye
Time frame: From Baseline to Month 12
Mean Change From Baseline Over Time in Central Sub-field Thickness (CSFT)
Time frame: Baseline, Month 3, Month 6, and Month 12
Number of Patients With CNV Leakage (Center Involvement) in the Study Eye at Baseline and Month 12
Time frame: From Baseline until Month 12
NEI-VFQ-25 - Change From Baseline to Month 3, 6 and 12
Time frame: Change from baseline at month 3, 6 and 12
Number of Ranibizumab Injections Received in the Study Eye for the Ranibizumab Groups
Time frame: From Baseline to Month 12

Results and safety

Results posted to the registry on 24 Jun 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Group I	182	173
Group II	184	175
Group III	91	83

Primary outcome: Change From Baseline BCVA to the Average Level of BCVA Over All Monthly Assessments From Month 1 to Month 3

Time frame: From Baseline to Month 3. Mean (Standard Deviation). Unit: ETDRS letters

Measure	Group I n = 182	Group II n = 184	Group III n = 91
Baseline	53.7 (12.65)	54.2 (13.01)	52.6 (12.29)
Average Month 1 to Month 3	63.1 (12.80)	63.9 (13.28)	57.1 (13.21)

Group I vs Group III: Mean Difference (Net): 5.2 (95% CI 3.3 to 7.1), p <0.001, Cochran-Mantel-Haenszel
Group II vs Group III: Mean Difference (Net): 5.6 (95% CI 3.5 to 7.6), p <0.001, Cochran-Mantel-Haenszel

Population analysed: Full Analysis Set (FAS): consisted of all patients to whom study treatment were assigned. Following the intent-to-treat principle, patients were analyzed according to the treatment group they were assigned to at randomization.

8 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Treatment, approximately 4 years.. Other adverse events reported at 1% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Group I	7 of 182 (3.8%)	102 of 182 (56%)	Not reported
Group II	15 of 185 (8.1%)	116 of 185 (62.7%)	Not reported
Group III With 0.5mg Ranibizumab	8 of 75 (10.7%)	50 of 75 (66.7%)	Not reported
Group III Without 0.5mg Ranibizumab	0 of 14 (0%)	8 of 14 (57.1%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 24 Jun 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: Undecided. Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Novartis Pharmaceuticals study director

Novartis Pharmaceuticals

47 sites in 6 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 47 sites in China, India, Thailand, South Korea, Philippines and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Jun 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline BCVA to the Average Level of BCVA Over All Monthly Assessments From Month 1 to Month 3 (time frame: From Baseline to Month 3). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01922102.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jun 2019.