Neovacular Age-related Macular DegenerationPhase 4UNRAVELNCT01988662

UNcovering the Difference Between Ranibizumab and Aflibercept, Focusing on Systemic Anti-vascular Endothelial Growth Factor (VEGF) Effects in Patients With neovascuLar Age-related Macular Degeneration (AMD)

A Phase 4 study testing Neovascular Age-related Macular Degeneration in people with Neovacular Age-related Macular Degeneration, run by Novartis Pharmaceuticals at 24 sites in 7 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 assessed systemic vascular endothelial growth factor (VEGF) level in patients with neovascular Age-related Macular Degeneration following treatment with Ranibizumab or Aflibercept. Free plasma VEGF-A level was measured in this study . Read more about this study

Who is it for?: Ages 50 years and older
Conditions the study is for: Neovacular Age-related Macular Degeneration
What is being tested?: Neovascular Age-related Macular Degeneration
Type of treatment: Injection or infusion, Surgery or procedure
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 205 participants
Where: 24 sitesin 7 countries
Study dates: Apr 2014to Sep 2015
Phase: Phase 4
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 50 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Newly diagnosed Age-related Macular Degeneration (AMD)
No previous treatment received for diagnosed AMD
Visual Acuity 6/7.5 to 6/96

Who cannot join

standard exclusion criteria for anti-VEGF treatment
Visual Acuity <6/96
nAMD in both eyes, or any condition in other eye which may have required anti- VEGF treatment during study period
other disease in candidate eye which could have compromised visual acuity or required medical/surgical intervention during study period
participation to other clinical study with 'not approved' treatment within a year prior to UNRAVEL study participation.

Trial locations and contacts

24 sites in 7 countries.

Country

City, postcode or hospital

24 sites in 7 countries

Israel7 sites

Novartis Investigative Site
Beersheba, 84101
Novartis Investigative Site
Haifa, 3436212
Novartis Investigative Site
Haifa, 3525408
Novartis Investigative Site
Kfar Saba, 4428164
Novartis Investigative Site
Petah Tikva, 49100
Novartis Investigative Site
Rehovot, 7610001
Novartis Investigative Site
Tel Aviv, 6423906

Other trials in Israel

South Korea5 sites

Novartis Investigative Site
Daegu, 705-703
Novartis Investigative Site
Seoul, Korea, 03722
Novartis Investigative Site
Seoul, Korea, 05505
Novartis Investigative Site
Seoul, 06273
Novartis Investigative Site
Seoul, 150-950

Other trials in South Korea

Philippines3 sites

Novartis Investigative Site
Makati City, 1209
Novartis Investigative Site
Pasig, 1605
Novartis Investigative Site
Quezon City, 1102

Other trials in Philippines

Thailand3 sites

Novartis Investigative Site
Bangkok, Bangkoknoi, 10700
Novartis Investigative Site
Bangkok, 10330
Novartis Investigative Site
Bangkok, 10400

Other trials in Thailand

Malaysia2 sites

Novartis Investigative Site
Kuala Lumpur, 59200
Novartis Investigative Site
Petaling Jaya, Selangor, 46200

Other trials in Malaysia

Singapore2 sites

Novartis Investigative Site
Singapore, Singapore, 117549
Novartis Investigative Site
Singapore, 574623

Other trials in Singapore

Taiwan2 sites

Novartis Investigative Site
Linkou District, 33305
Novartis Investigative Site
Taipei, Taiwan, 10002

Other trials in Taiwan

About this study

Official title: A 3 Months, patient-and Rater Blinded, Randomized, Prospective Study Comparing Systemic Anti-VEGF Effects Between Ranibizumab and Aflibercept in Treatment naïve Neovascular Age-related Macular Degeneration (nAMD) Patients

This study assessed systemic vascular endothelial growth factor (VEGF) level in patients with neovascular Age-related Macular Degeneration following treatment with Ranibizumab or Aflibercept.

Free plasma VEGF-A level was measured in this study .

Conditions: Neovacular Age-related Macular Degeneration
Being tested: Neovascular Age-related Macular Degeneration
Keywords: nAMD, VEGF, VEGF agent, BCVA, CRT, Ranibizumab, Lucentis, Aflibercept, Eylea
Medical subject headings: Creatine deficiency, X-linked

What participants receive

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

Neovascular Age-related Macular DegenerationProcedure or surgery
Also called Lucentis, Eylea
Blood measurement

Study groups in NCT01988662
Study group	Role	What they receive
Ranibizumab	Experimental	104 patients with an eligible study eye were randomized to be treated with Ranibizumab IVT. 0.5 mg of commercially available Ranibizumab were used for intravitreal injection adminstered by an unblinded injecting physician. 3 injections were performed (Baseline, Month 1, Month 2). Receives: Procedure: Neovascular Age-related Macular Degeneration
Aflibercept	Active comparator	101 patients with an eligible study eye were randomized to be treated with Aflibercept IVT. 2.0 mg of commercially available Aflibercept were used for intravitreal injection admistered by an unblinded injecting physician. 3 injections were performed (Baseline, Month 1, Month 2). Receives: Procedure: Neovascular Age-related Macular Degeneration

What is being measured

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

Percent Change From Baseline at Month 3 in Plasma VEGF Following Intravitreal (IVT) Injection of Anti-VEGF Agent
Percent change in blood VEGF level is calculated as the difference in blood VEGF level measured after 3 month of anti-VEGF agent IVT treatment (Ranibizumab or Aflibercept) when compared to baseline blood VEGF level.
Measured: Change from baseline at Month 3

Secondary outcomes (5)

Percent Change From Baseline in Plasma VEGF Level Overtime
Plasma VEGF measurement performed at all visits and compared to baseline level
Measured: Change from baseline up to month 3
Correlation Between Percent Change From Baseline Plasma VEGF Level and the Serum Anti-VEGF Agent Overtime
VEGF level and anti-VEGF concentration measured in the blood at each single visit, including pre- and post-dose measurement at the dosing visits.
Measured: pre-dose to post-dose at Baseline, week 1, week 2, month 1, month 2, and month 3
Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) of the Study Eye Over Time
BCVA score is assessed on study eye based on the number of letters read correctly on the Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity charts at a testing distance of 4 meters. An increase in score indicates an improvement in acuity. Change from baseline calculated as observed post-baseline value - baseline value.
Measured: Baseline, month 1, month 2, month 3
Mean Change From Baseline in Central Retinal Thickness (CRT) of the Study Eye Over Time
CRT in micrometers assessed by Optical Tomography (OCT) at each single study visit. A reduction is thickness indicates an improvement is the lesion area.
Change from baseline calculated as observed post-baseline - baseline value.
Measured: Baseline, month 1, month 2, month 3
Number of Patients With Ocular and Systemic Adverse Events
The incidence of reported treatment emergent adverse events (TEAEs) and treatment emergent serious adverse events (TESAE).
Measured: Day 1 to day 85

Timeline

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

Apr 2014Sep 2015

First posted20 Nov 2013 (estimated)
Study startApr 2014
Primary completionSep 2015
Study completionSep 2015

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 Neovacular Age-related Macular DegenerationStudies 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 4
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 205 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01988662
Sponsor's protocol ID: CRFB002A-MAX-IL-01
Other IDs: 2013-003482-34
Acronym: UNRAVEL
Status last verified: Mar 2017
First submitted: 14 Nov 2013
Last updated: 3 May 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Study at a glance

From the registry record, last updated by the sponsor on 3 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A 3 Months, patient-and Rater Blinded, Randomized, Prospective Study Comparing Systemic Anti-VEGF Effects Between Ranibizumab and Aflibercept in Treatment naïve Neovascular Age-related Macular Degeneration (nAMD) Patients
ClinicalTrials.gov ID: NCT01988662
Acronym / sponsor ID: UNRAVEL / CRFB002A-MAX-IL-01
Conditions: Neovacular Age-related Macular Degeneration
Keywords: nAMD, VEGF, VEGF agent, BCVA, CRT, Ranibizumab, Lucentis, Aflibercept, Eylea
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 205 participants (actual)
Lead sponsor: Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
Study start: Apr 2014
Primary completion: Sep 2015 (actual)
Study completion: Sep 2015 (actual)
First posted: 20 Nov 2013 (estimated)
Results: Posted 28 Feb 2017

Clinical summary

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

This study assessed systemic vascular endothelial growth factor (VEGF) level in patients with neovascular Age-related Macular Degeneration following treatment with Ranibizumab or Aflibercept.

Free plasma VEGF-A level was measured in this study .

Study design

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

Arm	Type	Receives
Ranibizumab	Experimental	Procedure: Neovascular Age-related Macular Degeneration104 patients with an eligible study eye were randomized to be treated with Ranibizumab IVT. 0.5 mg of commercially available Ranibizumab were used for intravitreal injection adminstered by an unblinded injecting physician. 3 injections were performed (Baseline, Month 1, Month 2).
Aflibercept	Active comparator	Procedure: Neovascular Age-related Macular Degeneration101 patients with an eligible study eye were randomized to be treated with Aflibercept IVT. 2.0 mg of commercially available Aflibercept were used for intravitreal injection admistered by an unblinded injecting physician. 3 injections were performed (Baseline, Month 1, Month 2).

Who may qualify

Ages: 50 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

Newly diagnosed Age-related Macular Degeneration (AMD)
No previous treatment received for diagnosed AMD
Visual Acuity 6/7.5 to 6/96

Key exclusion criteria (5 listed)

standard exclusion criteria for anti-VEGF treatment
Visual Acuity <6/96
nAMD in both eyes, or any condition in other eye which may have required anti- VEGF treatment during study period
other disease in candidate eye which could have compromised visual acuity or required medical/surgical intervention during study period
participation to other clinical study with 'not approved' treatment within a year prior to UNRAVEL study participation.

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
Neovascular Age-related Macular DegenerationAlso: Lucentis, EyleaBlood measurement	Procedure or surgery	Aflibercept, Ranibizumab

Primary outcome

Percent Change From Baseline at Month 3 in Plasma VEGF Following Intravitreal (IVT) Injection of Anti-VEGF Agent
Time frame: Change from baseline at Month 3
Percent change in blood VEGF level is calculated as the difference in blood VEGF level measured after 3 month of anti-VEGF agent IVT treatment (Ranibizumab or Aflibercept) when compared to baseline blood VEGF level.

5 secondary outcomes

Percent Change From Baseline in Plasma VEGF Level Overtime
Time frame: Change from baseline up to month 3
Correlation Between Percent Change From Baseline Plasma VEGF Level and the Serum Anti-VEGF Agent Overtime
Time frame: pre-dose to post-dose at Baseline, week 1, week 2, month 1, month 2, and month 3
Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) of the Study Eye Over Time
Time frame: Baseline, month 1, month 2, month 3
Mean Change From Baseline in Central Retinal Thickness (CRT) of the Study Eye Over Time
Time frame: Baseline, month 1, month 2, month 3
Number of Patients With Ocular and Systemic Adverse Events
Time frame: Day 1 to day 85

Results and safety

Results posted to the registry on 28 Feb 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	104	100
Aflibercept	101	99

Primary outcome: Percent Change From Baseline at Month 3 in Plasma VEGF Following Intravitreal (IVT) Injection of Anti-VEGF Agent

Time frame: Change from baseline at Month 3. Least squares mean (Standard Error). Unit: Percent change

Measure	Ranibizumab n = 100	Aflibercept n = 99
Value	41.04 (19.918)	-21.53 (20.398)

Ranibizumab vs Aflibercept: Mean Difference (Net): 62.57 (95% CI 13.96 to 111.17), p = 0.012, Mixed Models Analysis

Population analysed: Full Analysis Set (FAS): The FAS consisted of all randomized patients who received at least one dose of study treatment. FAS was the analysis set. However, patients who were randomized due to erroneous use of the IRT system and who did not receive at least one dose of study treatment were excluded from the FAS.

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: Throughout the study period (day 1 to day 85). Other adverse events reported at 1% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Ranibizumab	3 of 104 (2.9%)	20 of 104 (19.2%)	Not reported
Aflibercept	5 of 101 (5%)	19 of 101 (18.8%)	Not reported
Total	8 of 205 (3.9%)	39 of 205 (19%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 3 May 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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

24 sites in 7 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Neovascular Age-related Macular Degeneration in people with Neovacular Age-related Macular Degeneration, run by Novartis Pharmaceuticals at 24 sites in 7 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 3 inclusion and 5 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 3 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 24 sites in Israel, South Korea, Philippines, Thailand, Malaysia and 2 more countries. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

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 28 Feb 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?

Percent Change From Baseline at Month 3 in Plasma VEGF Following Intravitreal (IVT) Injection of Anti-VEGF Agent (time frame: Change from baseline at 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 NCT01988662.

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 3 May 2017.