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

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

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 (AMD).

Study Overview

• Status: Completed
• Conditions: Neovascular Age-Related Macular Degeneration
• Intervention / Treatment: Drug: Brolucizumab 3 mg/50 μL; Drug: Brolucizumab 6 mg/50 μL

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.

• Study Type: Interventional
• Enrollment (Actual): 51
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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;
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Brolucizumab 3 mg; 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	Drug: Brolucizumab 3 mg/50 μL; Administered as an intravitreal injection; Other Names: RTH258; ESBA1008
Experimental: Brolucizumab 6 mg; 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	Drug: Brolucizumab 6 mg/50 μL; Administered as an intravitreal injection; Other Names: RTH258; ESBA1008

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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.	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.	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.	Day 57

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Day 0 (predose), Day 28, Day 84

Collaborators and Investigators

• Sponsor: Alcon Research
• Investigators: Study Director: Alcon, A Novartis Division, Alcon, A Novartis Division

Study record dates

Study Major Dates

• Study Start (Actual): August 24, 2015
• Primary Completion (Actual): September 6, 2016
• Study Completion (Actual): September 6, 2016

Study Registration Dates

• First Submitted: July 22, 2015
• First Submitted That Met QC Criteria: July 22, 2015
• First Posted (Estimate): July 23, 2015

Study Record Updates

• Last Update Posted (Actual): July 2, 2018
• Last Update Submitted That Met QC Criteria: May 31, 2018
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: AMD; Age-Related Macular Degeneration; nAMD; wetAMD
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Wet Macular Degeneration
• Other Study ID Numbers: RTH258-E003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

IPD Plan Description

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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No