Macular Edema Secondary to Branch Retinal Vein OcclusionPhase 3BlossomNCT01976338

Ranibizumab Intravitreal Injections Versus Sham Control in Patients With Branch Retinal Vein Occlusion (BRVO)

A Phase 3 study testing Ranibizumab 0.5 mg in people with Macular Edema Secondary to Branch Retinal Vein Occlusion, run by Novartis Pharmaceuticals at 33 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

Provided efficacy and safety data on intravitreal injections of ranibizumab 0.5 mg in patients with visual impairment due to macular edema secondary to BRVO Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Macular Edema Secondary to Branch Retinal Vein Occlusion
What is being tested?: Ranibizumab 0.5 mg
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 283 participants
Where: 33 sitesin 6 countries
Study dates: 12 Nov 2013to 28 Mar 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

Patients with visual impairment secondary to branch retinal vein occlusion (BRVO) with a BCVA between 19 and 73 letters in one eye and at least 35 letters in the other eye.

Who cannot join

Pregnant or nursing women or women of child bearing potential without unless using an effective contraception
Stroke or myocard infarction within 3 months prior to study
History of malignancy within the past 5 years
Uncontrolled hypertension
Active infection or inflammation in any eye
use of corticosteroids for at least 30 days in the last 6 months
treatment with anti-angiogenic drugs in any eye within last 3 months
Panretinal or focal/drid laser photocoagulation within the last few months

Trial locations and contacts

33 sites in 6 countries.

Country

City, postcode or hospital

33 sites in 6 countries

China23 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, 410011
Novartis Investigative Site
Chengdu, Sichuan, 610041
Novartis Investigative Site
Chongqing, Chongqing Municipality, 400042
Novartis Investigative Site
Chongqing, 400038
Novartis Investigative Site
Guangzhou, Guangdong, 510060
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
Nantong, Jiangsu, 226000
Novartis Investigative Site
Qingdao, Shandong, 266011
Novartis Investigative Site
Shanghai, 200080
Novartis Investigative Site
Shanghai, 200092
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, 430070

Other trials in China

Taiwan3 sites

Novartis Investigative Site
Kaohsiung City, 83301
Novartis Investigative Site
Linkou District, 33305
Novartis Investigative Site
Taipei

Other trials in Taiwan

Indonesia2 sites

Novartis Investigative Site
Bandung, West Java, 40117
Novartis Investigative Site
Jakarta, Jakarta Special Capital Region, 10430

Other trials in Indonesia

Philippines2 sites

Novartis Investigative Site
Manila, National Capital Region, 1000
Novartis Investigative Site
San Juan City, Philippines, 1500

Other trials in Philippines

Vietnam2 sites

Novartis Investigative Site
Hanoi, Vietnam, 10000
Novartis Investigative Site
Ho Chi Minh City, Vietnam, 70000

Other trials in Vietnam

Hong Kong1 site

Novartis Investigative Site
Hong Kong, Hong Kong

Other trials in Hong Kong

About this study

Official title: A Randomized Double-masked, Phase III Study Assessing Ranibizumab Intravitreal Injections Versus Sham Control in Patients With Visual Impairment Due to Macular Edema (ME) Secondary to Branch Retinal Vein Occlusion (BRVO) [Blossom]

Provided efficacy and safety data on intravitreal injections of ranibizumab 0.5 mg in patients with visual impairment due to macular edema secondary to BRVO

Conditions: Macular Edema Secondary to Branch Retinal Vein Occlusion
Being tested: Ranibizumab 0.5 mg, Sham injection
Keywords: BRVO, macular edema, vision impairment, retinal vein occlusion, ranibizumab, branch retinal vein occlusion, anti-VEGF therapy, RFB002
Medical subject headings: Macular Edema, Vision Disorders, Retinal Vein Occlusion

What participants receive

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

Ranibizumab 0.5 mgDrug
intravitreal injection of 0.05 ml
Sham injectionOther
Also called Sham
Sham intravitreal injection

Study groups in NCT01976338
Study group	Role	What they receive
Ranibizumab 0.5 mg	Experimental	PRN Intravitreal injection Receives: Drug: Ranibizumab 0.5 mg
Sham injection	Sham comparator	As of Month 6 ranibizumab 0.5 mg PRN intravitreal injection Receives: Other: Sham injection

What is being measured

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

Average Change in Best Corrected Visual Acuity (BCVA) From Baseline to Month 1 Through Month 6
Best Corrected Visual Acuity (BCVA) was assessed in a sitting position using ETDRS-like visual acuity testing charts at an initial testing distance of 4 meters. Mean Visual Acuity was averaged over all monthly assessments from month 1 to month 6 and compared to Baseline.
Measured: Baseline to Month 1 through Month 6

Secondary outcomes (9)

Average Change of Best Corrected Visual Acuity (BCVA) in Patients From Baseline to Month 1 Through Month 12
Best Corrected Visual Acuity (BCVA) was assessed in a sitting position using ETDRS-like visual acuity testing charts at an initial testing distance of 4 meters. Mean Visual Acuity was averaged over all monthly assessments from month 1 to month 12 and compared to Baseline
Measured: Baseline to Month 1 through Month 12
Best Corrected Visual Acuity (BCVA) Change Over Time
Best Corrected Visual Acuity (BCVA) was assessed in a sitting position using ETDRS-like visual acuity testing charts at an initial testing distance of 4 meters. Mean Visual Acuity was averaged over all monthly assessments from month 1 to month 12 and compared to Baseline
Measured: Month 1 through Month 12
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time
Best Corrected Visual Acuity (BCVA) was assessed in a sitting position using ETDRS-like visual acuity testing charts at an initial testing distance of 4 meters
Measured: Baseline to month 12
Number of Participants With Best Corrected Visual Acuity (BCVA)Loss of 15 Letters in the Study Eye
Visual acuity (VA) was assessed at every study visit using best correction determined from protocol refraction. VA measurements (number of letters correctly identified) were performed with the patient in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts at a testing distance of 4 meters. This outcome measure describes for each post-baseline month whether or not a patient lost less than 15 letters of VA as compared with baseline.
Measured: Baseline to 12 months
Change in Central-Sub-Field- Thickness (CSFT) Over Time
OCT (optical coherence tomography) was used to assess CSFT (Central Sub-Field Thickness) representing the average retinal thickness of the circular area within 1 mm diameter around the foveal center
Measured: Month 1 to month 12
Change in Total Area of Fluorescein Leakage (Center Subfield) From Baseline Over Time
Fluorescein leakage area was assessed using Fluorescein angiography (FA) in conjunction with 7-field color fundus photography (CF) at Screening, Month 3, Month 6 and End of Study visit for both eyes
Measured: month 3, 6 and 12
Change in Total Area of Fluorescein Leakage (Inner Subfield) From Baseline Over Time
Fluorescein leakage area was assessed using Fluorescein angiography (FA) in conjunction with 7-field color fundus photography (CF) at Screening, Month 3, Month 6 and End of Study visit for both eyes
Measured: Months 3, 6 and 12
Change in Total Area of Fluorescein Leakage (Outer Subfield) From Baseline Over Time
Fluorescein leakage area was assessed using Fluorescein angiography (FA) in conjunction with 7-field color fundus photography (CF) at Screening, Month 3, Month 6 and End of Study visit for both eyes
Measured: Months 3, 6 and 12
Change From Baseline in NEI-VFQ-25 Composite and Subscale Scores at Month 3, Month 6 and Month 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: Baseline, months 3, 6 and 12

Timeline

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

12 Nov 201328 Mar 2016

First posted5 Nov 2013 (estimated)
Study start12 Nov 2013
Primary completion28 Mar 2016
Study completion28 Mar 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.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Macular Edema Secondary to Branch Retinal Vein OcclusionStudies 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: Double blind
Who is masked: Participant, Outcomes assessor
Enrolment: 283 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01976338
Sponsor's protocol ID: CRFB002E2303
Acronym: Blossom
Status last verified: Mar 2017
First submitted: 18 Oct 2013
Last updated: 8 May 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Wei W, Weisberger A, Zhu L, Cheng Y, Liu C; BLOSSOM Study Group. Efficacy and Safety of Ranibizumab in Asian Patients with Branch Retinal Vein Occlusion: Results from the Randomized BLOSSOM Study. Ophthalmol Retina. 2020 Jan;4(1):57-66. doi: 10.1016/j.oret.2019.08.001. Epub 2019 Aug 13.
PubMed 31902472

Study at a glance

From the registry record, last updated by the sponsor on 8 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized Double-masked, Phase III Study Assessing Ranibizumab Intravitreal Injections Versus Sham Control in Patients With Visual Impairment Due to Macular Edema (ME) Secondary to Branch Retinal Vein Occlusion (BRVO) [Blossom]
ClinicalTrials.gov ID: NCT01976338
Acronym / sponsor ID: Blossom / CRFB002E2303
Conditions: Macular Edema Secondary to Branch Retinal Vein Occlusion
Keywords: BRVO, macular edema, vision impairment, retinal vein occlusion, ranibizumab, branch retinal vein occlusion, anti-VEGF therapy, RFB002
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 283 participants (actual)
Lead sponsor: Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
Study start: 12 Nov 2013 (actual)
Primary completion: 28 Mar 2016 (actual)
Study completion: 28 Mar 2016 (actual)
First posted: 5 Nov 2013 (estimated)
Results: Posted 8 May 2017

Clinical summary

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

Provided efficacy and safety data on intravitreal injections of ranibizumab 0.5 mg in patients with visual impairment due to macular edema secondary to BRVO

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Ranibizumab 0.5 mg	Experimental	Drug: Ranibizumab 0.5 mgPRN Intravitreal injection
Sham injection	Sham comparator	Other: Sham injectionAs of Month 6 ranibizumab 0.5 mg PRN intravitreal injection

Who may qualify

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

Key inclusion criteria (1 listed)

Patients with visual impairment secondary to branch retinal vein occlusion (BRVO) with a BCVA between 19 and 73 letters in one eye and at least 35 letters in the other eye.

Key exclusion criteria (8 listed)

Pregnant or nursing women or women of child bearing potential without unless using an effective contraception
Stroke or myocard infarction within 3 months prior to study
History of malignancy within the past 5 years
Uncontrolled hypertension
Active infection or inflammation in any 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 0.5 mgintravitreal injection of 0.05 ml	Drug	Ranibizumab 0.5 mg
Sham injectionAlso: ShamSham intravitreal injection	Other	Sham injection

Primary outcome

Average Change in Best Corrected Visual Acuity (BCVA) From Baseline to Month 1 Through Month 6
Time frame: Baseline to Month 1 through Month 6
Best Corrected Visual Acuity (BCVA) was assessed in a sitting position using ETDRS-like visual acuity testing charts at an initial testing distance of 4 meters. Mean Visual Acuity was averaged over all monthly assessments from month 1 to month 6 and compared to Baseline.

9 secondary outcomes

Average Change of Best Corrected Visual Acuity (BCVA) in Patients From Baseline to Month 1 Through Month 12
Time frame: Baseline to Month 1 through Month 12
Best Corrected Visual Acuity (BCVA) Change Over Time
Time frame: Month 1 through Month 12
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time
Time frame: Baseline to month 12
Number of Participants With Best Corrected Visual Acuity (BCVA)Loss of 15 Letters in the Study Eye
Time frame: Baseline to 12 months
Change in Central-Sub-Field- Thickness (CSFT) Over Time
Time frame: Month 1 to month 12
Change in Total Area of Fluorescein Leakage (Center Subfield) From Baseline Over Time
Time frame: month 3, 6 and 12
Change in Total Area of Fluorescein Leakage (Inner Subfield) From Baseline Over Time
Time frame: Months 3, 6 and 12
Change in Total Area of Fluorescein Leakage (Outer Subfield) From Baseline Over Time
Time frame: Months 3, 6 and 12
Change From Baseline in NEI-VFQ-25 Composite and Subscale Scores at Month 3, Month 6 and Month 12
Time frame: Baseline, months 3, 6 and 12

Results and safety

Results posted to the registry on 8 May 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Ranibizumab 0.5 mg	190	177
Sham Injection	93	89

Primary outcome: Average Change in Best Corrected Visual Acuity (BCVA) From Baseline to Month 1 Through Month 6

Time frame: Baseline to Month 1 through Month 6. Mean (Standard Deviation). Unit: Letters

Measure	Ranibizumab 0.5 mg n = 189	Sham Injection n = 93
Value	12.5 (8.34)	5.0 (9.18)

Ranibizumab 0.5 mg vs Sham Injection: p <0.001, Cochran-Mantel-Haenszel

Population analysed: The Full Analysis Set (FAS) consisted of all patients to whom study treatment had been assigned. Following the intent-to-treat principle, patients were analyzed according to the treatment group they had been assigned to at randomization. Mean value interpolation and last observation carried forward (MV-LOCF)

9 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 1% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Ranibizumab 0.5 mg	13 of 190 (6.8%)	119 of 190 (62.6%)	Not reported
Sham With Ranibizumab 0.5 mg	3 of 66 (4.5%)	46 of 66 (69.7%)	Not reported
Sham Without Ranibizumab 0.5 mg	3 of 26 (11.5%)	14 of 26 (53.8%)	Not reported

Limitations and caveats (from the sponsor): One patient was randomized to the ranibizumab group but received no study treatment during the study period and discontinued the study after Visit 2. Therefore, excluded from the Safety set

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 8 May 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 31902472Wei W, Weisberger A, Zhu L, Cheng Y, Liu C; BLOSSOM Study Group. Efficacy and Safety of Ranibizumab in Asian Patients with Branch Retinal Vein Occlusion: Results from the Randomized BLOSSOM Study. Ophthalmol Retina. 2020 Jan;4(1):57-66. doi: 10.1016/j.oret.2019.08.001. Epub 2019 Aug 13.

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

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

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Ranibizumab 0.5 mg in people with Macular Edema Secondary to Branch Retinal Vein Occlusion, run by Novartis Pharmaceuticals at 33 sites in 6 countries.

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 1 inclusion and 8 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 8 May 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 33 sites in China, Taiwan, Indonesia, Philippines, Vietnam 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. Some participants in this study may receive a placebo. 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 8 May 2017). 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?

Average Change in Best Corrected Visual Acuity (BCVA) From Baseline to Month 1 Through Month 6 (time frame: Baseline to Month 1 through Month 6). 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 NCT01976338, which also lists 1 linked publication.

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 8 May 2017.