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Trial record 2 of 18 for:    RTH258

Efficacy and Safety of RTH258 Versus Aflibercept - Study 1 (HAWK)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02307682
Recruitment Status : Completed
First Posted : December 4, 2014
Results First Posted : October 31, 2019
Last Update Posted : January 13, 2020
Sponsor:
Information provided by (Responsible Party):
Alcon Research

Tracking Information
First Submitted Date  ICMJE November 21, 2014
First Posted Date  ICMJE December 4, 2014
Results First Submitted Date  ICMJE October 8, 2019
Results First Posted Date  ICMJE October 31, 2019
Last Update Posted Date January 13, 2020
Actual Study Start Date  ICMJE December 8, 2014
Actual Primary Completion Date April 22, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 8, 2019)
Change From Baseline in Best Corrected Visual Acuity (BCVA) (Letters Read) at Week 48 - Study Eye [ Time Frame: Baseline, Week 48 ]
BCVA (with spectacles or other visual corrective devices) was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) testing at 4 meters and reported in letters read correctly. Baseline was defined as the last measurement prior to first treatment. An increase (gain) in letters read from the baseline assessment indicates improvement. One eye (study eye) contributed to the analysis.
Original Primary Outcome Measures  ICMJE
 (submitted: December 3, 2014)
Change in Best Corrected Visual Acuity (BCVA) from Baseline at Week 48 [ Time Frame: Baseline, Week 48 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 8, 2019)
  • Average Change From Baseline in BCVA (Letters Read) Over the Period Week 36 Through Week 48 - Study Eye [ Time Frame: Baseline, Weeks 36, 40, 44, 48 ]
    BCVA (with spectacles or other visual corrective devices) was assessed using ETDRS testing at 4 meters and reported in letters read correctly. For each subject, this endpoint was defined as the average of the changes from baseline to Weeks 36, 40, 44, and 48. Baseline was defined as the last measurement prior to first treatment. An increase (gain) in letters read from the baseline assessment indicates improvement. One eye (study eye) contributed to the analysis.
  • Proportion of Subjects With Positive q12 (Every 12 Weeks) Treatment Status at Week 48 [ Time Frame: Weeks 16, 20, 28, 32, 40, 44, 48 ]
    Positive q12 treatment status was defined as IVT injections per planned dosing regimen (one injection every 12 weeks "q12w", after the initial three loading injections every 4 weeks "q4w"). A disease activity assessment (DAA) was performed at pre-specified visits (Weeks 16, 20, 28, 32, 40, 44) to identify q8w (one injection every 8 weeks) need. The estimate for the proportion of subjects with a positive q12w status at Week 48 were derived from Kaplan-Meier time to event analyses for the event of first q8w need, applying event allocations (in case of lack of efficacy and/or lack of safety=efficacy/safety approach) and censoring as described in the SAP. Censored subjects were considered to be not anymore under risk for a q8 need identification at later visits. Corresponding 95% Confidence Intervals (CIs) were derived from the LOGLOG transformation. No hypothesis testing was performed. This outcome measure was pre-specified for brolucizumab 3mg and 6 mg arms only.
  • Proportion of Subjects With Positive q12 Treatment Status at Week 48 Within the Subjects With no q8 (Every 8 Weeks) Treatment Need During the First q12 Cycle (Week 16, Week 20) [ Time Frame: Weeks 16, 20, 28, 32, 40, 44, 48 ]
    Positive q12 treatment status was defined as IVT injections per planned dosing regimen (one injection every 12 weeks "q12w", after the initial three loading injections every 4 weeks "q4w"). A DAA was performed at pre-specified visits (Weeks 16, 20, 28, 32, 40, 44) to identify q8w need. The estimate for the proportion of subjects with a positive q12w status at Week 48 were derived from Kaplan-Meier time to event analyses for the event of first q8w need, applying event allocations (in case of lack of efficacy and/or lack of safety=efficacy/safety approach) and censoring as described in the SAP. Censored subjects were considered to be not anymore under risk for a q8 need identification at later visits. Corresponding 95% CIs were derived from the LOGLOG transformation. No hypothesis testing was performed. This outcome measure was pre-specified for the brolucizumab 3 mg and 6 mg arms only.
  • Proportion of Subjects With Positive q12 Treatment Status up to Week 96 [ Time Frame: Weeks 16, 20, 28, 32, 40, 44, 52, 56, 64, 68, 76, 80, 88, 92, 96 ]
    Positive q12 treatment status was defined as IVT injections per planned dosing regimen (one injection every 12 weeks "q12w", after the initial three loading injections every 4 weeks "q4w"). A DAA was performed at pre-specified visits (Weeks 16, 20, 28, 32, 40, 44, 52, 56, 64, 68, 76, 80, 88, 92) to identify q8w need. The estimate for the proportion of subjects with a positive q12w status at Week 48 were derived from Kaplan-Meier time to event analyses for the event of first q8w need, applying event allocations (in case of lack of efficacy and/or lack of safety=efficacy/safety approach) and censoring as described in the SAP. Censored subjects were considered to be not anymore under risk for a q8 need identification at later visits. Corresponding 95% CIs were derived from the LOGLOG transformation. No hypothesis testing was performed. This outcome measure was pre-specified for the brolucizumab 3 mg and 6 mg arms only.
  • Proportion of Subjects With Positive q12 Treatment Status at Week 96 Within the Subjects With no q8 Treatment Need During the Initial q12 Cycle (Week 16, Week 20) [ Time Frame: Weeks 16, 20, 28, 32, 40, 44, 52, 56, 64, 68, 76, 80, 88, 92, 96 ]
    Positive q12 treatment status was defined as IVT injections per planned dosing regimen (one injection every 12 weeks "q12w", after the initial three loading injections every 4 weeks "q4w"). A DAA was performed at pre-specified visits (Weeks 16, 20, 28, 32, 40, 44, 52, 56, 64, 68, 76, 80, 88, 92) to identify q8w need. The estimate for the proportion of subjects with a positive q12w status at Week 48 were derived from Kaplan-Meier time to event analyses for the event of first q8w need, applying event allocations (in case of lack of efficacy and/or lack of safety=efficacy/safety approach) and censoring as described in the SAP. Censored subjects were considered to be not anymore under risk for a q8 need identification at later visits. Corresponding 95% CIs were derived from the LOGLOG transformation. No hypothesis testing was performed. This outcome measure was pre-specified for the brolucizumab 3 mg and 6 mg arms only.
  • Change From Baseline in BCVA (Letters Read) at Each Post-baseline Visit - Study Eye [ Time Frame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96 ]
    BCVA (with spectacles or other visual corrective devices) was assessed using ETDRS testing at 4 meters and reported in letters read correctly. Baseline was defined as the last measurement prior to first treatment. An increase (gain) in letters read from the baseline assessment indicates improvement. One eye (study eye) contributed to the analysis.
  • Average Change From Baseline in BCVA (Letters Read) Over the Period Week 4 to Week 48/96 - Study Eye [ Time Frame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96 ]
    BCVA (with spectacles or other visual corrective devices) was assessed using ETDRS testing at 4 meters and reported in letters read correctly. Baseline was defined as the last measurement prior to first treatment. An increase (gain) in letters read from the baseline assessment indicates improvement. One eye (study eye) contributed to the analysis.
  • Average Change From Baseline in BCVA (Letters Read) Over the Period Week 12 to Week 48/96 - Study Eye [ Time Frame: Baseline, Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96 ]
    BCVA (with spectacles or other visual corrective devices) was assessed using ETDRS testing at 4 meters and reported in letters read correctly. Baseline was defined as the last measurement prior to first treatment. An increase (gain) in letters read from the baseline assessment indicates improvement. One eye (study eye) contributed to the analysis.
  • Average Change From Baseline in BCVA (Letters Read) Over the Period Week 84 to Week 96 - Study Eye [ Time Frame: Baseline, Weeks 84, 88, 92, 96 ]
    BCVA (with spectacles or other visual corrective devices) was assessed using ETDRS testing at 4 meters and reported in letters read correctly. Baseline was defined as the last measurement prior to first treatment. An increase (gain) in letters read from the baseline assessment indicates improvement. One eye (study eye) contributed to the analysis.
  • Percentage of Subjects With >=15 Letter Gain From Baseline in BCVA (Letters Read) at Each Post-baseline Visit - Study Eye [ Time Frame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96 ]
    BCVA (with spectacles or other visual corrective devices) was assessed using ETDRS testing at 4 meters and reported in letters read correctly. Baseline was defined as the last measurement prior to first treatment. An increase (gain) in letters read from the baseline assessment indicates improvement. 95% CI for binomial proportions was based on Clopper-Pearson exact method. One eye (study eye) contributed to the analysis.
  • Percentage of Subjects With >=10 Letter Gain From Baseline in BCVA (Letters Read) at Each Post-baseline Visit - Study Eye [ Time Frame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96 ]
    BCVA (with spectacles or other visual corrective devices) was assessed using ETDRS testing at 4 meters and reported in letters read correctly. Baseline was defined as the last measurement prior to first treatment. An increase (gain) in letters read from the baseline assessment indicates improvement. 95% CI for binomial proportions was based on Clopper-Pearson exact method. One eye (study eye) contributed to the analysis.
  • Percentage of Subjects With >=5 Letter Gain From Baseline in BCVA (Letters Read) at Each Post-baseline Visit - Study Eye [ Time Frame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96 ]
    BCVA (with spectacles or other visual corrective devices) was assessed using ETDRS testing at 4 meters and reported in letters read correctly. Baseline was defined as the last measurement prior to first treatment. An increase (gain) in letters read from the baseline assessment indicates improvement. 95% CI for binomial proportions was based on Clopper-Pearson exact method. One eye (study eye) contributed to the analysis.
  • Percentage of Subjects With >=15 Letter Loss From Baseline in BCVA (Letters Read) at Each Post-baseline Visit - Study Eye [ Time Frame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96 ]
    BCVA (with spectacles or other visual corrective devices) was assessed using ETDRS testing at 4 meters and reported in letters read correctly. Baseline was defined as the last measurement prior to first treatment. An increase (gain) in letters read from the baseline assessment indicates improvement. 95% CI for binomial proportions was based on Clopper-Pearson exact method. One eye (study eye) contributed to the analysis.
  • Percentage of Subjects With >=10 Letter Loss From Baseline in BCVA (Letters Read) at Each Post-baseline Visit - Study Eye [ Time Frame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96 ]
    BCVA (with spectacles or other visual corrective devices) was assessed using ETDRS testing at 4 meters and reported in letters read correctly. Baseline was defined as the last measurement prior to first treatment. An increase (gain) in letters read from the baseline assessment indicates improvement. 95% CI for binomial proportions was based on Clopper-Pearson exact method. One eye (study eye) contributed to the analysis.
  • Percentage of Subjects With >=5 Letter Loss From Baseline in BCVA (Letters Read) at Each Post-baseline Visit - Study Eye [ Time Frame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96 ]
    BCVA (with spectacles or other visual corrective devices) was assessed using ETDRS testing at 4 meters and reported in letters read correctly. Baseline was defined as the last measurement prior to first treatment. An increase (gain) in letters read from the baseline assessment indicates improvement. 95% CI for binomial proportions was based on Clopper-Pearson exact method. One eye (study eye) contributed to the analysis.
  • Percentage of Subjects With BCVA of 73 Letters Read or More at Each Visit - Study Eye [ Time Frame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96 ]
    BCVA (with spectacles or other visual corrective devices) was assessed using ETDRS testing at 4 meters and reported in letters read correctly (0-100 letters). A score of 65 to 70 letters represents a low to moderate visual acuity. Baseline was defined as the last measurement prior to first treatment. 95% CI for binomial proportions was based on Clopper-Pearson exact method. One eye (study eye) contributed to the analysis.
  • Change From Baseline in Central Subfield Thickness (CSFTtot) at Each Post-baseline Visit - Study Eye [ Time Frame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96 ]
    CSFTtot (the average retinal thickness of the circular area within 1 millimeter diameter around the foveal center) was assessed using Spectral-Domain Optical Coherence Tomography (SD-OCT), a non-invasive measurement which produces cross-sectional and 3-dimensional images of the eye. A negative change value indicates an improvement, while a positive change value indicates a worsening. One eye (study eye) contributed to the analysis.
  • Average Change From Baseline in CSFTtot Over the Period Week 36 Through Week 48 - Study Eye [ Time Frame: Baseline, Weeks 36, 40, 44, 48 ]
    CSFTtot (the average retinal thickness of the circular area within 1 millimeter diameter around the foveal center) was assessed using SD-OCT, a non-invasive measurement which produces cross-sectional and 3-dimensional images of the eye. A negative change value indicates an improvement, while a positive change value indicates a worsening. One eye (study eye) contributed to the analysis.
  • Average Change From Baseline in CSFTtot Over the Period Week 84 Through Week 96 - Study Eye [ Time Frame: Baseline, Weeks 84, 88, 92, 96 ]
    CSFTtot (the average retinal thickness of the circular area within 1 millimeter diameter around the foveal center) was assessed using SD-OCT, a non-invasive measurement which produces cross-sectional and 3-dimensional images of the eye. A negative change value indicates an improvement, while a positive change value indicates a worsening. One eye (study eye) contributed to the analysis.
  • Average Change From Baseline in CSFTtot Over the Period Week 4 Through Week 48/96 - Study Eye [ Time Frame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96 ]
    CSFTtot (the average retinal thickness of the circular area within 1 millimeter diameter around the foveal center) was assessed using SD-OCT, a non-invasive measurement which produces cross-sectional and 3-dimensional images of the eye. A negative change value indicates an improvement, while a positive change value indicates a worsening. One eye (study eye) contributed to the analysis.
  • Change From Baseline in Choroidal Neovascularization (CNV) Lesion Size at Week 12, Week 48, and Week 96 - Study Eye [ Time Frame: Baseline, Weeks 12, 48, 96 ]
    CNV lesion size (the area of new blood vessels in the choroid layer of the retina) size was measured using fluorescein angiography (FA). A negative change value indicates a reduction in lesion size, whereas a positive change value indicates an increase. An increase in CNV lesion size may indicate progression of the underlying disease. Only one eye (study eye) contributed to the analysis.
  • Change From Baseline in Central Subfield Neurosensory Retinal Thickness (CSFTns) at Each Post-baseline Visit - Study Eye [ Time Frame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96 ]
    Central subfield neurosensory retinal thickness was assessed using SD-OCT. A negative change value indicates an improvement, while a positive change value indicates a worsening. One eye (study eye) contributed to the analysis.
  • Percentage of Subjects With Presence of Subretinal Fluid at Each Post-baseline Visit - Study Eye [ Time Frame: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96 ]
    Subretinal fluid was assessed using SD-OCT and recorded as Present/Absent. The presence of subretinal fluid is an indicator of underlying disease. 95% CI for binomial proportions was based on Clopper-Pearson exact method. One eye (study eye) contributed to the analysis.
  • Percentage of Subjects With Presence of Intraretinal Fluid at Each Post-baseline Visit - Study Eye [ Time Frame: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96 ]
    Intraretinal fluid was assessed using SD-OCT and recorded as Present/Absent. The presence of intraretinal fluid is an indicator of underlying disease. 95% CI for binomial proportions was based on Clopper-Pearson exact method. One eye (study eye) contributed to the analysis.
  • Percentage of Subjects With Presence of Sub-retinal Pigment Epithelium (RPE) Fluid at Each Post-baseline Visit - Study Eye [ Time Frame: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96 ]
    Sub-RPE fluid was assessed using SD-OCT and recorded as Present/Absent. The presence of sub-RPE fluid is an indicator of underlying disease. 95% CI for binomial proportions was based on Clopper-Pearson exact method. One eye (study eye) contributed to the analysis.
  • Percentage of Subjects With Presence of Subretinal and/or Intraretinal Fluid at Each Post-baseline Visit - Study Eye [ Time Frame: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96 ]
    Subretinal fluid and intraretinal fluid were assessed using SD-OCT and recorded as Present/Absent. The presence of subretinal and/or intraretinal fluid is an indicator of underlying disease. 95% CI for binomial proportions was based on Clopper-Pearson exact method. One eye (study eye) contributed to the analysis.
  • Number of Subjects With Subretinal Fluid (SRF) and/or Intraretinal Fluid (IRF) Present Between Week 36 to Week 48, Reported by Number of Visits [ Time Frame: Weeks 36, 40, 44, 48 ]
    Subretinal fluid and intraretinal fluid were assessed using SD-OCT and recorded as Present/Absent. The presence of subretinal and/or intraretinal fluid is an indicator of underlying disease. One eye (study eye) contributed to the analysis. For each subject, the number of visits with SRF and/or IRF fluid is analyzed.
  • Percentage of Subjects With Disease Activity Present (q8 Treatment Need = "Yes") at Week 16 - Study Eye [ Time Frame: Week 16 ]
    A disease activity assessment (DAA) was performed to identify q8 treatment need. 95% CI for binomial proportions is based on Clopper-Pearson exact method. One eye (study eye) contributed to the analysis.
  • Change From Baseline in Visual Function Questionnaire (VFQ-25) Composite Score at Week 24, Week 48, Week 72, and Week 96 [ Time Frame: Baseline, Weeks 24, 48, 72, 96 ]
    The National Eye Institute Visual Function Questionnaire-25 (VFQ-25) is a validated questionnaire that collects 25 vision-targeted responses from age-related macular degeneration (AMD) subjects. The 25 questions pertain to global vision rating (1), difficulty with near vision activities (3), difficulty with distance vision activities (3), limitations in social functioning due to vision (2), role limitations due to vision (2), dependency on others due to vision (3), mental health symptoms due to vision (4), driving difficulties (3), limitations with peripheral (1) and color vision (1), and ocular pain (2). Each response is converted to a 0 to 100 sub-scale, with the lowest and highest possible scores set at 0 and 100 points, respectively. The overall composite score (0 to 100) is obtained by averaging the 25 sub-scale scores. A high score represents better functioning.
  • Percentage of Subjects With Induced or Boosted Anti-drug Antibody (ADA) Status at Week 48 (Brolucizumab Only) [ Time Frame: Week 48 ]
    Serum samples were collected and assessed for anti-drug antibody status. Subjects were categorized as ADA negative when one of the following was met: ADA negative at all time points (predose and postdose); ADA negative at predose and no titer values above 10 at all other time points; or ADA titer of 10 at predose but negative at all other time points. ADA induced was defined as ADA negative at predose with postdose titer value greater than or equal to a titer of 30 at any timepoint. ADA boosted was defined as ADA positive at predose with postdose titer values that increased by at least two dilutions (9-fold) from their respective predose value at any time point. Hypothesis testing not pre-specified.
  • Percentage of Subjects With Intraretinal Hemorrhage (Central Subfield) Present at the Visit While Absent at Baseline at Each Treatment - Study Eye [ Time Frame: Baseline, Weeks 12, 48, 96 ]
    Intraretinal hemorrhage was assessed using SD-OCT and recorded as Present/Absent. The presence of intraretinal hemorrhage is an indicator of underlying disease. 95% CI for binomial proportions was based on Clopper-Pearson exact method. One eye (study eye) contributed to the analysis. Hypothesis testing not pre-specified.
  • Percentage of Subjects With Subretinal Hemorrhage (Central Subfield) Present at the Visit While Absent at Baseline at Each Treatment - Study Eye [ Time Frame: Baseline, Weeks 12, 48, 96 ]
    Subretinal hemorrhage was assessed using SD-OCT and recorded as Present/Absent. The presence of subretinal hemorrhage is an indicator of underlying disease. 95% CI for binomial proportions was based on Clopper-Pearson exact method. One eye (study eye) contributed to the analysis. Hypothesis testing not pre-specified.
Original Secondary Outcome Measures  ICMJE
 (submitted: December 3, 2014)
  • Average Change in BCVA from Baseline over the Period Week 36 through Week 48 [ Time Frame: Baseline, Week 36 through Week 48 ]
  • Treatment Response [ Time Frame: Week 16 through Week 48 ]
  • Change in BCVA from Baseline at Each Postbaseline Visit [ Time Frame: Baseline, up to Week 96 ]
  • Average Change in BCVA from Baseline over the Period Week 4 to Week 48 [ Time Frame: Baseline, Week 4 to Week 48 ]
  • Gain in BCVA of 15/10/5 Letters or More from Baseline to each Postbaseline Visit [ Time Frame: Baseline, up to Week 96 ]
  • Loss in BCVA of 15/10/5 Letters or More from Baseline to each Postbaseline Visit [ Time Frame: Baseline, up to Week 96 ]
  • Change in Central Subfield Thickness (CSFT) from Baseline to each Postbaseline Visit [ Time Frame: Baseline, up to Week 96 ]
  • Change in Area of CNV from Baseline to Weeks 48 and 96 [ Time Frame: Baseline, Week 48, Week 96 ]
  • Absence of any Subretinal, Intraretinal or Sub Retinal Pigment Epithelium (RPE) Fluid at each Postbaseline Visit [ Time Frame: Up to Week 96 ]
  • Presence of Neovascular AMD Disease Activity According to Protocol Defined Criteria at Weeks 16, 20, 32, 44, 56, 68 and 80 [ Time Frame: Week 16 to Week 80 ]
  • Change in Patient Reported Outcomes from Baseline to Weeks 24, 48, 72 and 96 [ Time Frame: Baseline, Week 24 to Week 96 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy and Safety of RTH258 Versus Aflibercept - Study 1
Official Title  ICMJE A Two-Year, Randomized, Double-Masked, Multicenter, Three-Arm Study Comparing the Efficacy and Safety of RTH258 Versus Aflibercept in Subjects With Neovascular Age-Related Macular Degeneration
Brief Summary The purpose of this study is to compare brolucizumab (RTH258) ophthalmic solution for intravitreal (IVT) injection at two dosage levels (3 mg and 6 mg) to aflibercept ophthalmic solution for IVT injection (2 mg) in subjects with untreated active choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) in the study eye.
Detailed Description

Subjects were randomized to brolucizumab 3 mg, brolucizumab 6 mg,and aflibercept 2 mg in a 1:1:1 ratio. Subjects in all treatment arms received 3 monthly loading doses (Day 0, Week 4 and Week 8), followed by a maintenance regimen, until the end of the study (Week 96/Exit). All subjects attended pre-specified visits every 4 weeks.

Subjects in the brolucizumab 3 mg and brolucizumab 6 mg arms followed a q12w/q8w maintenance regimen. Within the q12w/q8w regimen, the initial treatment after the loading phase was q12w (1 injection every 12 weeks). If disease activity was identified by the masked investigator at any of the disease activity assessments, dosing was adjusted to q8w (1 injection every 8 weeks) ("q12w/q8w regimen"). Once subjects were adjusted to the q8w interval, they stayed on that interval until the end of the study.

Subjects in the aflibercept 2 mg arm followed a q8w maintenance regimen until the end of the study.

Results reported up to Week 48 are based on the database locked for the primary analysis at Week 48. Results reported after Week 48 are based on the database locked at the end of study (final analysis).

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Neovascular Age-Related Macular Degeneration
  • Choroidal Neovascularization
Intervention  ICMJE
  • Drug: Brolucizumab ophthalmic solution
    Ophthalmic solution for IVT injection
    Other Name: RTH258
  • Drug: Aflibercept ophthalmic solution
    Ophthalmic solution for IVT injection
    Other Name: EYLEA®
Study Arms  ICMJE
  • Experimental: Brolucizumab 3 mg
    Single intravitreal (IVT) injection of brolucizumab ophthalmic solution administered as a 3 mg/50 microliter (μL) dose at Day 0, Week 4, and Week 8, followed by 1 injection every 8 weeks/1 injection every 12 weeks (q8w/q12w) maintenance regimen until study exit
    Intervention: Drug: Brolucizumab ophthalmic solution
  • Experimental: Brolucizumab 6 mg
    Single IVT injection of brolucizumab ophthalmic solution administered as a 6 mg/50 μL dose at Day 0, Week 4, and Week 8, followed by q8w/q12w maintenance regimen until study exit
    Intervention: Drug: Brolucizumab ophthalmic solution
  • Active Comparator: Aflibercept 2 mg
    Single IVT injection of aflibercept ophthalmic solution administered as a 2 mg/50 μL dose at Day 0, Week 4, and Week 8, followed by q8w maintenance regimen until study exit
    Intervention: Drug: Aflibercept ophthalmic solution
Publications * Dugel PU, Koh A, Ogura Y, Jaffe GJ, Schmidt-Erfurth U, Brown DM, Gomes AV, Warburton J, Weichselberger A, Holz FG; HAWK and HARRIER Study Investigators. HAWK and HARRIER: Phase 3, Multicenter, Randomized, Double-Masked Trials of Brolucizumab for Neovascular Age-Related Macular Degeneration. Ophthalmology. 2020 Jan;127(1):72-84. doi: 10.1016/j.ophtha.2019.04.017. Epub 2019 Apr 12.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 8, 2018)
1775
Original Estimated Enrollment  ICMJE
 (submitted: December 3, 2014)
990
Actual Study Completion Date  ICMJE March 28, 2018
Actual Primary Completion Date April 22, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria:

  • Provide written informed consent
  • Active choroidal neovascularization (CNV) lesions secondary to age-related macular degeneration (AMD) that affected the central subfield in the study eye at Screening;
  • Total area of CNV comprising >50% of the total lesion area in the study eye at Screening;
  • Intraretinal and/or subretinal fluid affecting the central subfield of the study eye at Screening;
  • Best Corrected Visual Acuity (BCVA) between 78 and 23 letters, inclusive, in the study eye at Screening and Baseline using Early Treatment Diabetic Retinopathy Study (ETDRS) testing.

Key Exclusion Criteria:

  • Any active intraocular or periocular infection or active intraocular inflammation in either eye at Baseline;
  • Central subfield of the study eye affected by fibrosis or geographic atrophy or total area of fibrosis >50% of the total lesion in the study eye at Screening;
  • Subretinal blood affecting the foveal center point and/or >50% of the lesion of the study eye at Screening;
  • Any approved or investigational treatment for neovascular age-related macular degeneration (nAMD) in the study eye at any time;
  • Retinal pigment epithelial rip/tear in the study eye at Screening or Baseline or current vitreous hemorrhage or history of vitreous hemorrhage in the study eye within 4 weeks prior to Baseline;
  • Pregnant or nursing women; women of child-bearing potential;
  • Stroke or myocardial infarction in the 90-day period prior to Baseline.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 50 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02307682
Other Study ID Numbers  ICMJE RTH258-C001
CRTH258A2301 ( Other Identifier: Novartis Pharmaceuticals )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
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.
Responsible Party Alcon Research
Study Sponsor  ICMJE Alcon Research
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Group Trial Lead Novartis Pharmaceuticals
PRS Account Alcon Research
Verification Date October 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP