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

NCT02507388 | Completed Phase 2 Results FDA Drug

• 1 other identifier: RTH258-E003
• Study Type: interventional
• Target: 51
• Locations: 0 countries
• Sites: N/A

Brief 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 (AMD).

Conditions

Neovascular Age-Related Macular Degeneration

Keywords

AMD; nAMD; wetAMD; Age-Related Macular Degeneration

Outcome Measures

Primary Outcomes (7)

• 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 Outcomes (1)

• Percentage of Subjects With Positive Anti-drug Antibody (ADA) Status (Test)

  Day 0 (predose), Day 28, Day 84

Study Arms (2)

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

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

Drug: Brolucizumab 6 mg/50 μL

Interventions

Brolucizumab 3 mg/50 μL DRUG

Administered as an intravitreal injection

Also known as: RTH258, ESBA1008

Brolucizumab 3 mg

Brolucizumab 6 mg/50 μL DRUG

Administered as an intravitreal injection

Also known as: RTH258, ESBA1008

Brolucizumab 6 mg

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• years of age or older at the time of Screening.

You may not qualify if:

• 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;

Sponsors & Collaborators

• Alcon Research: lead

MeSH Terms

Conditions

Macular Degeneration

Interventions

brolucizumab

Condition Hierarchy (Ancestors)

Retinal Degeneration; Retinal Diseases; Eye Diseases

Limitations and Caveats

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.

Results Point of Contact

• Title: Global Program Clinical Head, Ophthalmology
• Organization: Alcon, A Novartis Division

alcon.medinfo@alcon.com

1-888-451-3937

Study Officials

• Alcon, A Novartis Division

  Alcon, A Novartis Division

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 22, 2015
• First Posted: July 23, 2015
• Study Start: August 24, 2015
• Primary Completion: September 6, 2016
• Study Completion: September 6, 2016
• Last Updated: July 2, 2018
• Results First Posted: September 29, 2017

Record last verified: 2017-09