Back to resultsSafety and Pharmacokinetics of RTH258 in Subjects With Age-Related Macular Degeneration
Primary Purpose
Neovascular Age-Related Macular Degeneration
Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Brolucizumab 3 mg/50 μL
Brolucizumab 6 mg/50 μL
Sponsored by
About this trial
This is an interventional other trial for Neovascular Age-Related Macular Degeneration focused on measuring AMD, nAMD, wetAMD, Age-Related Macular Degeneration
Eligibility Criteria
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.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Brolucizumab 3 mg
Brolucizumab 6 mg
Arm Description
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
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
Outcomes
Primary Outcome Measures
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.
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.
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.
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.
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.
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.
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.
Secondary Outcome Measures
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02507388
Brief Title
Safety and Pharmacokinetics of RTH258 in Subjects With Age-Related Macular Degeneration
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
Study Type
Interventional
2. Study Status
Record Verification Date
September 2017
Overall Recruitment Status
Completed
Study Start Date
August 24, 2015 (Actual)
Primary Completion Date
September 6, 2016 (Actual)
Study Completion Date
September 6, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Alcon Research
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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).
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neovascular Age-Related Macular Degeneration
Keywords
AMD, nAMD, wetAMD, Age-Related Macular Degeneration
7. Study Design
Primary Purpose
Other
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
51 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Brolucizumab 3 mg
Arm Type
Experimental
Arm Description
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
Arm Title
Brolucizumab 6 mg
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Brolucizumab 3 mg/50 μL
Other Intervention Name(s)
RTH258, ESBA1008
Intervention Description
Administered as an intravitreal injection
Intervention Type
Drug
Intervention Name(s)
Brolucizumab 6 mg/50 μL
Other Intervention Name(s)
RTH258, ESBA1008
Intervention Description
Administered as an intravitreal injection
Primary Outcome Measure Information:
Title
Maximum Analyte Serum Concentration [Cmax (ng/mL)]
Description
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 Frame
Day 0 (predose), 6 hr, 24 hr, 72 hr, 168 hr, 336 hr, 504 hr, 672 hr
Title
Time to Reach Maximum Analyte Serum Concentration [Tmax (h)]
Description
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 Frame
Day 0 (predose), 6 hr, 24 hr, 72 hr, 168 hr, 336 hr, 504 hr, 672 hr
Title
Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration [AUC0-tlast (ng*h/mL)]
Description
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 Frame
Day 0 (predose), 6 hr, 24 hr, 72 hr, 168 hr, 336 hr, 504 hr, 672 hr
Title
Area Under the Concentration-time Curve From 0 to Infinity [AUC0-inf (ng*h/mL)]
Description
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 Frame
Day 0 (predose), 6 hr, 24 hr, 72 hr, 168 hr, 336 hr, 504 hr, 672 hr
Title
Elimination Half-life in Serum [t1/2 (h)]
Description
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 Frame
Day 0 (predose), 6 hr, 24 hr, 72 hr, 168 hr, 336 hr, 504 hr, 672 hr
Title
Concentration of RTH258 Obtained 24 Hours Post Day 0 Injection [C24hr (ng/mL)]
Description
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.
Time Frame
Day 1
Title
Concentration of RTH258 Obtained 24 Hours Post Day 56 Injection [C24hr (ng/mL)]
Description
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.
Time Frame
Day 57
Secondary Outcome Measure Information:
Title
Percentage of Subjects With Positive Anti-drug Antibody (ADA) Status (Test)
Description
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.
Time Frame
Day 0 (predose), Day 28, Day 84
10. Eligibility
Sex
All
Minimum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alcon, A Novartis Division
Organizational Affiliation
Alcon, A Novartis Division
Official's Role
Study Director
12. IPD Sharing Statement
Plan to Share IPD
Undecided
IPD Sharing 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.
Learn more about this trial
Safety and Pharmacokinetics of RTH258 in Subjects With Age-Related Macular Degeneration
We'll reach out to this number within 24 hrs