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

Neovascular Age-Related Macular Degeneration Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02507388
• Other study ID #: RTH258-E003
• Status: Completed
• Phase: Phase 2
• Start date: August 24, 2015
• Est. completion date: September 6, 2016

Study information

• Verified date: September 2017
• Source: Alcon Research
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 (AMD).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 51
• Est. completion date: September 6, 2016
• Est. primary completion date: September 6, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Macular Degeneration
• Neovascular Age-Related Macular Degeneration
• Wet Macular Degeneration

Intervention

Drug:
• Brolucizumab 3 mg/50 µL
Administered as an intravitreal injection
• Brolucizumab 6 mg/50 µL
Administered as an intravitreal injection

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Alcon Research

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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

External Links

•   Results from the Novartis Clinical Trial Results Website