Neovascular Age-Related Macular DegenerationPhase 2NCT02507388

Safety and Pharmacokinetics of RTH258 in Subjects With Age-Related Macular Degeneration

A Phase 2 study testing Brolucizumab 3 mg/50 μL and Brolucizumab 6 mg/50 μL in people with Neovascular Age-Related Macular Degeneration, run by Alcon Research.

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

The purpose of this study is to assess the systemic pharmacokinetics (PK) and safety of 2 different doses of brolucizumab (3 milligrams (mg)/50 microliters (μL) and 6 mg/50 μL) when administered at 4-week intervals for a total of 3 intravitreal injections in subjects with neovascular age-related macular degeneration… Read more about this study

Who is it for?: Ages 50 years and older
Conditions the study is for: Neovascular Age-Related Macular Degeneration
What is being tested?: Brolucizumab 3 mg/50 μL and Brolucizumab 6 mg/50 μL
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 51 participants
Where: No sites listed yet
Study dates: 24 Aug 2015to 6 Sep 2016
Phase: Phase 2
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

Provide written informed consent;
Active choroidal neovascularization (CNV) lesions secondary to AMD that affect the central subfield in the study eye;
Best Corrected Visual Acuity (BCVA) > 23 letters in the study eye at Baseline;
50 years of age or older at the time of Screening.

Who cannot join

Any active ocular infection or inflammation;
Treatment with aflibercept (EYLEA®), bevacizumab (AVASTIN®), ranibizumab (LUCENTIS®), brolucizumab, or an investigational drug for neovascular AMD prior to enrollment in the study, as specified in protocol;
Ocular surgery in the study eye, as specified in protocol;
Uncontrolled glaucoma in the study eye, as specified in protocol;
Use of steroids in the study eye, as specified in protocol;
Medical conditions that may prevent study completion;

Show all 10Show fewer

Pregnant or nursing (lactating) women;
Women of child-bearing potential unless using contraception;
Uncontrolled blood pressure, as specified in protocol;
Other protocol-specified exclusion criteria may apply.

About this study

Official title: A Randomized, Double Masked, Three Dose Safety and Pharmacokinetic Study of RTH258 Following Intravitreal (IVT) Injection in Subjects With Neovascular Age-Related Macular Degeneration

Read the detailed description

This study has 2 arms with a 1:1 randomization. Randomization will be stratified by Japanese ethnicity. Half of the subjects in each arm will be of Japanese ethnicity. The other half of the subjects in each arm will be non-Japanese. Subjects in both arms will have visits at Screening, Day 0 (Baseline), Day 1 (24 hours post first injection), Day 3, Day 14, Day 21, Day 28, Day 56, Day 57 (24 hours post the injection on Day 56) and Day 84.

Conditions: Neovascular Age-Related Macular Degeneration
Being tested: Brolucizumab 3 mg/50 μL, Brolucizumab 6 mg/50 μL
Keywords: AMD, nAMD, wetAMD, Age-Related Macular Degeneration
Medical subject headings: Macular Degeneration

What participants receive

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

Brolucizumab 3 mg/50 μLDrug
Also called RTH258, ESBA1008
Administered as an intravitreal injection
Brolucizumab 6 mg/50 μLDrug
Also called RTH258, ESBA1008
Administered as an intravitreal injection

Study groups in NCT02507388
Study group	Role	What they receive
Brolucizumab 3 mg	Experimental	Brolucizumab 3 mg/50 μL administered as an intravitreal injection 3 times at 4-week intervals with follow-up for 84 days from the initial injection Receives: Drug: Brolucizumab 3 mg/50 μL
Brolucizumab 6 mg	Experimental	Brolucizumab 6 mg/50 μL administered as an intravitreal injection 3 times at 4-week intervals with follow-up for 84 days from the initial injection Receives: Drug: Brolucizumab 6 mg/50 μL

What is being measured

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

Maximum Analyte Serum Concentration [Cmax (ng/mL)]
Serum concentrations at each collection time point were quantitated, where possible, using a validated immunoassay method. These data were analyzed using a noncompartmental pharmacokinetic (PK) method.
Measured: Day 0 (predose), 6 hr, 24 hr, 72 hr, 168 hr, 336 hr, 504 hr, 672 hr
Time to Reach Maximum Analyte Serum Concentration [Tmax (h)]
Serum concentrations at each collection time point were quantitated, where possible, using a validated immunoassay method. These data were analyzed using a noncompartmental pharmacokinetic (PK) method.
Measured: Day 0 (predose), 6 hr, 24 hr, 72 hr, 168 hr, 336 hr, 504 hr, 672 hr
Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration [AUC0-tlast (ng*h/mL)]
Serum concentrations at each collection time point were quantitated, where possible, using a validated immunoassay method. These data were analyzed using a noncompartmental pharmacokinetic (PK) method.
Measured: Day 0 (predose), 6 hr, 24 hr, 72 hr, 168 hr, 336 hr, 504 hr, 672 hr
Area Under the Concentration-time Curve From 0 to Infinity [AUC0-inf (ng*h/mL)]
Serum concentrations at each collection time point were quantitated, where possible, using a validated immunoassay method. These data were analyzed using a noncompartmental pharmacokinetic (PK) method.
Measured: Day 0 (predose), 6 hr, 24 hr, 72 hr, 168 hr, 336 hr, 504 hr, 672 hr
Elimination Half-life in Serum [t1/2 (h)]
Serum concentrations at each collection time point were quantitated, where possible, using a validated immunoassay method. These data were analyzed using a noncompartmental pharmacokinetic (PK) method.
Measured: Day 0 (predose), 6 hr, 24 hr, 72 hr, 168 hr, 336 hr, 504 hr, 672 hr
Concentration of RTH258 Obtained 24 Hours Post Day 0 Injection [C24hr (ng/mL)]
Serum concentration at the specified collection time point was quantitated, where possible, using a validated immunoassay method. The data were analyzed using a noncompartmental pharmacokinetic (PK) method.
Measured: Day 1
Concentration of RTH258 Obtained 24 Hours Post Day 56 Injection [C24hr (ng/mL)]
Serum concentration at the specified collection time point was quantitated, where possible, using a validated immunoassay method. The data were analyzed using a noncompartmental pharmacokinetic (PK) method.
Measured: Day 57

Secondary outcomes (1)

Percentage of Subjects With Positive Anti-drug Antibody (ADA) Status (Test)
A positive ADA status is defined as induced ADA status with ADA negative at predose and with a post-dose titer value increase of 2 or more dilutions at any time point or boosted ADA status with ADA positive at predose and a post-dose titer value increase by more than 3-fold (1 dilution) at any time point.
Measured: Day 0 (predose), Day 28, Day 84

Timeline

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

24 Aug 20156 Sep 2016

First posted23 Jul 2015 (estimated)
Study start24 Aug 2015
Primary completion6 Sep 2016
Study completion6 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 Neovascular Age-Related Macular DegenerationStudies of the same condition, open and under way.
More trials run by Alcon ResearchThe 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 2
Primary purpose: Other
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 51 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02507388
Sponsor's protocol ID: RTH258-E003
Status last verified: Sep 2017
First submitted: 22 Jul 2015
Last updated: 2 Jul 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
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.

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

RecruitingPhase 3
A Study of 36-Week Refill Exchanges of Port Delivery System (PDS) With Ranibizumab in nAMD
Neovascular Age-related Macular Degeneration
Active, not recruitingObservational study
Real World Evidence in China: Faricimab Use in Diabetic Macular Edema, Retinal Vein Occlusion, and Neovascular Age-Related Macular Degeneration (The Farseeing Study)
Diabetic Macular Edema, Neovascular Age-related Macular Degeneration
Active, not recruitingPhase 1/2
Phase 1/2 Study of VOY-101 in Patients With Advanced Non-Neovascular Age-Related Macular Degeneration
Age-Related Macular Degeneration, Geographic Atrophy
Active, not recruitingPhase 3
A Study to Evaluate the Efficacy and Safety of Tarcocimab Tedromer and Tabirafusp Tedromer Compared to Aflibercept in Participants With Neovascular (Wet) Age-related Macular Degeneration (wAMD) - DAYBREAK
Wet Age-related Macular Degeneration
Not yet recruitingPhase 2
A Study to Evaluate the Efficacy and Safety of VIS-101 in Participants With Neovascular Age-Related Macular Degeneration
Neovascular Age Related Macular Degeneration(nAMD)

All Neovascular Age-Related Macular Degeneration trials

Study at a glance

From the registry record, last updated by the sponsor on 2 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized, Double Masked, Three Dose Safety and Pharmacokinetic Study of RTH258 Following Intravitreal (IVT) Injection in Subjects With Neovascular Age-Related Macular Degeneration
ClinicalTrials.gov ID: NCT02507388
Acronym / sponsor ID: RTH258-E003
Conditions: Neovascular Age-Related Macular Degeneration
Keywords: AMD, nAMD, wetAMD, Age-Related Macular Degeneration
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 51 participants (actual)
Lead sponsor: Alcon ResearchIndustry (pharma, biotech, devices)
Study start: 24 Aug 2015 (actual)
Primary completion: 6 Sep 2016 (actual)
Study completion: 6 Sep 2016 (actual)
First posted: 23 Jul 2015 (estimated)
Results: Posted 29 Sep 2017

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

Arm	Type	Receives
Brolucizumab 3 mg	Experimental	Drug: Brolucizumab 3 mg/50 μLBrolucizumab 3 mg/50 μL administered as an intravitreal injection 3 times at 4-week intervals with follow-up for 84 days from the initial injection
Brolucizumab 6 mg	Experimental	Drug: Brolucizumab 6 mg/50 μLBrolucizumab 6 mg/50 μL administered as an intravitreal injection 3 times at 4-week intervals with follow-up for 84 days from the initial injection

Who may qualify

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

Key inclusion criteria (4 listed)

Provide written informed consent;
Active choroidal neovascularization (CNV) lesions secondary to AMD that affect the central subfield in the study eye;
Best Corrected Visual Acuity (BCVA) > 23 letters in the study eye at Baseline;
50 years of age or older at the time of Screening.

Key exclusion criteria (10 listed)

Any active ocular infection or inflammation;
Treatment with aflibercept (EYLEA®), bevacizumab (AVASTIN®), ranibizumab (LUCENTIS®), brolucizumab, or an investigational drug for neovascular AMD prior to enrollment in the study, as specified in protocol;
Ocular surgery in the study eye, as specified in protocol;
Uncontrolled glaucoma in the study eye, as specified in protocol;
Use of steroids in the study eye, as specified in protocol;

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
Brolucizumab 3 mg/50 μLAlso: RTH258, ESBA1008Administered as an intravitreal injection	Drug	Brolucizumab 3 mg
Brolucizumab 6 mg/50 μLAlso: RTH258, ESBA1008Administered as an intravitreal injection	Drug	Brolucizumab 6 mg

Primary outcome

Maximum Analyte Serum Concentration [Cmax (ng/mL)]
Time frame: Day 0 (predose), 6 hr, 24 hr, 72 hr, 168 hr, 336 hr, 504 hr, 672 hr
Serum concentrations at each collection time point were quantitated, where possible, using a validated immunoassay method. These data were analyzed using a noncompartmental pharmacokinetic (PK) method.
Time to Reach Maximum Analyte Serum Concentration [Tmax (h)]
Time frame: Day 0 (predose), 6 hr, 24 hr, 72 hr, 168 hr, 336 hr, 504 hr, 672 hr
Serum concentrations at each collection time point were quantitated, where possible, using a validated immunoassay method. These data were analyzed using a noncompartmental pharmacokinetic (PK) method.
Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration [AUC0-tlast (ng*h/mL)]
Time frame: Day 0 (predose), 6 hr, 24 hr, 72 hr, 168 hr, 336 hr, 504 hr, 672 hr
Serum concentrations at each collection time point were quantitated, where possible, using a validated immunoassay method. These data were analyzed using a noncompartmental pharmacokinetic (PK) method.
Area Under the Concentration-time Curve From 0 to Infinity [AUC0-inf (ng*h/mL)]
Time frame: Day 0 (predose), 6 hr, 24 hr, 72 hr, 168 hr, 336 hr, 504 hr, 672 hr
Serum concentrations at each collection time point were quantitated, where possible, using a validated immunoassay method. These data were analyzed using a noncompartmental pharmacokinetic (PK) method.
Elimination Half-life in Serum [t1/2 (h)]
Time frame: Day 0 (predose), 6 hr, 24 hr, 72 hr, 168 hr, 336 hr, 504 hr, 672 hr
Serum concentrations at each collection time point were quantitated, where possible, using a validated immunoassay method. These data were analyzed using a noncompartmental pharmacokinetic (PK) method.
Concentration of RTH258 Obtained 24 Hours Post Day 0 Injection [C24hr (ng/mL)]
Time frame: Day 1
Serum concentration at the specified collection time point was quantitated, where possible, using a validated immunoassay method. The data were analyzed using a noncompartmental pharmacokinetic (PK) method.
Concentration of RTH258 Obtained 24 Hours Post Day 56 Injection [C24hr (ng/mL)]
Time frame: Day 57
Serum concentration at the specified collection time point was quantitated, where possible, using a validated immunoassay method. The data were analyzed using a noncompartmental pharmacokinetic (PK) method.

1 secondary outcome

Percentage of Subjects With Positive Anti-drug Antibody (ADA) Status (Test)
Time frame: Day 0 (predose), Day 28, Day 84

Results and safety

Results posted to the registry on 29 Sep 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
Brolucizumab 3 mg	25	25
Brolucizumab 6 mg	25	25

Primary outcome: Maximum Analyte Serum Concentration [Cmax (ng/mL)]

Time frame: Day 0 (predose), 6 hr, 24 hr, 72 hr, 168 hr, 336 hr, 504 hr, 672 hr. Mean (Standard Deviation). Unit: ng/mL

Measure	Brolucizumab 3 mg n = 25	Brolucizumab 6 mg n = 25
Value	20.7 (29.4)	77.6 (105)

Population analysed: The PK analysis set included all subjects who received an intravitreal (IVT) injection with evaluable PK data and with no major protocol deviations that could have had an impact on the PK analysis.

Primary outcome: Time to Reach Maximum Analyte Serum Concentration [Tmax (h)]

Time frame: Day 0 (predose), 6 hr, 24 hr, 72 hr, 168 hr, 336 hr, 504 hr, 672 hr. Mean (Standard Deviation). Unit: hours

Measure	Brolucizumab 3 mg n = 25	Brolucizumab 6 mg n = 25
Value	20.3 (24.6)	17.4 (14.7)

Population analysed: PK analysis set

Primary outcome: Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration [AUC0-tlast (ng*h/mL)]

Time frame: Day 0 (predose), 6 hr, 24 hr, 72 hr, 168 hr, 336 hr, 504 hr, 672 hr. Mean (Standard Deviation). Unit: ng*h/mL

Measure	Brolucizumab 3 mg n = 25	Brolucizumab 6 mg n = 25
Value	2480 (5470)	9160 (12300)

Population analysed: PK analysis set

Primary outcome: Area Under the Concentration-time Curve From 0 to Infinity [AUC0-inf (ng*h/mL)]

Time frame: Day 0 (predose), 6 hr, 24 hr, 72 hr, 168 hr, 336 hr, 504 hr, 672 hr. Mean (Standard Deviation). Unit: ng*h/mL

Measure	Brolucizumab 3 mg n = 17	Brolucizumab 6 mg n = 24
Value	3380 (6860)	9770 (12600)

Population analysed: PK analysis set

1 secondary outcome is reported in the full results.

Adverse events

Time frame: Adverse events (AEs) were collected from time of consent for the duration of a subject's participation in the study (up to 105 days). AEs are reported as pre-treatment and treatment-emergent.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Pre-Treatment	0 of 50 (0%)	2 of 50 (4%)	0 of 50
Brolucizumab 3 mg	2 of 25 (8%)	10 of 25 (40%)	0 of 25
Brolucizumab 6 mg	1 of 25 (4%)	11 of 25 (44%)	0 of 25

Limitations and caveats (from the sponsor): Missing AUCinf and half life values attributable to concentration values below LLOQ may result in biased estimates. Causality assessment of the ADA status is limited due to the high number of subjects with positive ADA at baseline.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2018.
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.

Related trials for Neovascular Age-Related Macular Degeneration

RecruitingPhase 3
A Study of 36-Week Refill Exchanges of Port Delivery System (PDS) With Ranibizumab in nAMD
Neovascular Age-related Macular Degeneration
Active, not recruitingObservational study
Real World Evidence in China: Faricimab Use in Diabetic Macular Edema, Retinal Vein Occlusion, and Neovascular Age-Related Macular Degeneration (The Farseeing Study)
Diabetic Macular Edema, Neovascular Age-related Macular Degeneration
Active, not recruitingPhase 1/2
Phase 1/2 Study of VOY-101 in Patients With Advanced Non-Neovascular Age-Related Macular Degeneration
Age-Related Macular Degeneration, Geographic Atrophy
Active, not recruitingPhase 3
A Study to Evaluate the Efficacy and Safety of Tarcocimab Tedromer and Tabirafusp Tedromer Compared to Aflibercept in Participants With Neovascular (Wet) Age-related Macular Degeneration (wAMD) - DAYBREAK
Wet Age-related Macular Degeneration
Not yet recruitingPhase 2
A Study to Evaluate the Efficacy and Safety of VIS-101 in Participants With Neovascular Age-Related Macular Degeneration
Neovascular Age Related Macular Degeneration(nAMD)

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.

Alcon, A Novartis Division study director

Alcon, A Novartis Division

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Brolucizumab 3 mg/50 μL and Brolucizumab 6 mg/50 μL in people with Neovascular Age-Related Macular Degeneration, run by Alcon Research.

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 4 inclusion and 10 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 2 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.

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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 29 Sep 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?

Maximum Analyte Serum Concentration [Cmax (ng/mL)] (time frame: Day 0 (predose), 6 hr, 24 hr, 72 hr, 168 hr, 336 hr, 504 hr, 672 hr). The study lists 7 primary outcomes in all. 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 NCT02507388.

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 2 Jul 2018.