Study of Efficacy and Safety of Brolucizumab Versus Panretinal Photocoagulation Laser in Patients With Proliferative Diabetic Retinopathy
- Conditions
- Proliferative Diabetic Retinopathy
- Interventions
- Procedure: Panretinal photocoagulation laser
- Registration Number
- NCT04278417
- Lead Sponsor
- Novartis Pharmaceuticals
- Brief Summary
The purpose of this study was to evaluate the efficacy and safety of brolucizumab compared to panretinal photocoagulation laser (PRP) in patients with proliferative diabetic retinopathy (PDR). This evaluation will provide information that brolucizumab is non-inferior to PRP with respect to the change in best corrected visual acuity at Week 54.
- Detailed Description
Phase III, 96-week, two-arm, randomized (1:1 ratio), single-masked, multi-center, active-controlled study to evaluate the efficacy and safety of brolucizumab compared to Panretinal photocoagulation (PRP) in subjects with Proliferative diabetic retinopathy (PDR).
Subjects who consented underwent screening assessments to evaluate their eligibility based on the inclusion and exclusion criteria. Subjects who met all the inclusion and none of the exclusion criteria were randomized in a 1:1 ratio to one of the following treatments:
Brolucizumab 6 mg: 3 x q6w loading then q12w maintenance through Week 90, with the option from Week 48 onwards to extend the treatment interval by 6 weeks at a time up to 24 weeks, and revert to q12w if disease worsens. More frequent injection with q6w interval in the maintenance phase could be administered at the discretion of the Investigator if the disease worsens.
PRP: initial treatment in 1-4 sessions up to Week 12, followed with additional PRP treatment (may split into 2-4 sessions) as needed up to Week 90.
Visits occurred every 6 weeks throughout the study, regardless of treatment or not.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 689
- Signed informed consent must be obtained prior to participation
- Able to complete adequate fundus photographs and retinal images
- Diagnosis of type 1 or 2 Diabetes Mellitus (DM) and HbA1c less than or equal to 12% at screening
- DM treatment stable for at least 3 months
- PDR diagnosis with no previous PRP treatment in the study eye
- Concomitant conditions or ocular disorders in the study eye at Screening or Baseline that could compromise a response to study treatment.
- Presence of diabetic macular edema in the study eye
- Active infection or inflammation in the study eye
- Uncontrolled glaucoma (IOP greater than 25 mmHg)
- Intravitreal anti-VEGF treatment within 6 months
- Treatment with intraocular corticosteroids
- End stage renal disease requiring dialysis or kidney transplant
- Uncontrolled blood pressure
- Systemic anti-VEGF therapy at any time
Other protocol-defined inclusion/exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Panretinal photocoagulation laser Arm Panretinal photocoagulation laser Initial treatment in 1-4 sessions up to Week 12, followed with additional PRP treatment as needed Brolucizumab 6 mg Brolucizumab 6 mg Intra-vitreal injection. 3 x q6w loading injections, followed by q12w maintenance through Week 90
- Primary Outcome Measures
Name Time Method Change From Baseline in Best-corrected Visual Acuity (BCVA) at Week 54 for the Study Eye Baseline, Week 54 BCVA was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts.
Visual function of the study eye was assessed using the ETDRS protocol. Participants with a BCVA ETDRS letter score of \>= 34 ETDRS letters (Snellen equivalent 20/200) at Screening / Baseline in the study eye were included.
Min and max possible scores are 0-100 respectively. A higher score represents better functioning.
Last observation carried forward (LOCF) was used for the imputation of missing values.
- Secondary Outcome Measures
Name Time Method Number and Percentage of Subjects With no Proliferative Diabetic Retinopathy (PDR) at Week 54 for the Study Eye Week 54 Proliferative diabetic retinopathy (PDR) is derived from the diabetic retinopathy severity scale (DRSS) as assessed by the central reading center (CRC) using 7-field color fundus photography image. The DRSS on the original score with scores varying from 10 (DR absent) to 85 (very advanced PDR) were then converted into a 12-level scale (Range is from 1 - diabetic retinopathy (DR) absent, to 12- very advanced PDR). (A lower score represents a better outcome.) The event of "No PDR" is then defined as DRSS (12-level scale) \< 7.
Number and Percentage of Subjects With no Proliferative Diabetic Retinopathy (PDR) at Week 96 for the Study Eye Week 96 Proliferative diabetic retinopathy (PDR) is derived from the diabetic retinopathy severity scale (DRSS) as assessed by the central reading center (CRC) using 7-field color fundus photography image. The DRSS on the original score with scores varying from 10 (DR absent) to 85 (very advanced PDR) were then converted into a 12-level scale (Range is from 1 - diabetic retinopathy (DR) absent, to 12- very advanced PDR). (A lower score represents a better outcome.) The event of "No PDR" is then defined as DRSS (12-level scale) \< 7.
Number and Percentage of Subjects With Center-involved Diabetic Macular Edema (CI- DME) up to Week 54 for the Study Eye Up to Week 54 Assessed by Spectral domain optical coherence tomography (SD-OCT) from the central reading center.
PRP = Panretinal photocoagulation laserNumber and Percentage of Subjects With Center-involved Diabetic Macular Edema (CI- DME) up to Week 96 for the Study Eye Up to Week 96 Assessed by Spectral domain optical coherence tomography (SD-OCT) from the central reading center.
PRP = Panretinal photocoagulation laserArea Under the Curve in Change From Baseline in BCVA up to Week 54 and up to Week 96 - for the Study Eye Baseline, up to Week 54 and up to Week 96 BCVA was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts.
Visual function of the study eye was assessed using the ETDRS protocol. Participants with a BCVA ETDRS letter score of \>= 34 ETDRS letters (Snellen equivalent 20/200) at Screening / Baseline in the study eye were included.
Min and max possible scores are 0-100 respectively. A higher score represents better functioning.
Last observation carried forward (LOCF) was used for the imputation of missing values.
The AUC in change from Baseline in BCVA up to Week 54 (or Week 96) is referred to as the averaged change from Baseline in BCVA at each visit up to 54 (or Week 96), which was calculated as (BCVA at Week 6 + BCVA at Week 12 + ... + BCVA at Week 54 (or Week 96)) / number of visits with valid BCVA data from Week 6 to Week 54 (or Week 96) - BCVA at Baseline.Diabetic Retinopathy Severity Scale (DRSS): Number and Percentage of Subjects With ≥2 Steps Improvement From Baseline in Early Treatment Diabetic Retinopathy Study (ETDRS) DRSS Score at Week 54 and Week 96 Baseline, Week 54 and Week 96 Severity of Diabetic retinopathy was evaluated using the ETDRS DRSS score assessed by the Central Reading Center based on color fundus photography images in the study eye. When the ETDRS-DR severities were evaluable, they were categorized on the original scale with scores varying from 10 (DR absent) to 85 (very advanced PDR). All DRSS values were then converted into a 12-level scale, allowing the derivation of the ≥2-step and ≥3-step change from baseline for each post-baseline assessment".
A lower score represents better functioning.Diabetic Retinopathy Severity Scale (DRSS): Number and Percentage of Subjects With ≥2 Steps Worsening From Baseline in Early Treatment Diabetic Retinopathy Study (ETDRS) DRSS Score at Week 54 and Week 96 Baseline, Week 54 and Week 96 Severity of Diabetic retinopathy was evaluated using the ETDRS DRSS score assessed by the Central Reading Center based on color fundus photography images in the study eye. When the ETDRS-DR severities were evaluable, they were categorized on the original scale with scores varying from 10 (DR absent) to 85 (very advanced PDR). All DRSS values were then converted into a 12-level scale, allowing the derivation of the ≥2-step and ≥3-step change from baseline for each post-baseline assessment".
A lower score represents better functioning.Diabetic Retinopathy Severity Scale (DRSS): Number and Percentage of Subjects With ≥3 Steps Improvement From Baseline in Early Treatment Diabetic Retinopathy Study (ETDRS) DRSS Score at Week 54 and Week 96 Baseline, Week 54 and Week 96 Severity of Diabetic retinopathy was evaluated using the ETDRS DRSS score assessed by the Central Reading Center based on color fundus photography images in the study eye. When the ETDRS-DR severities were evaluable, they were categorized on the original scale with scores varying from 10 (DR absent) to 85 (very advanced PDR). All DRSS values were then converted into a 12-level scale, allowing the derivation of the ≥2-step and ≥3-step change from baseline for each post-baseline assessment".
A lower score represents better functioning.Diabetic Retinopathy Severity Scale (DRSS): Number and Percentage of Subjects With ≥3 Steps Worsening From Baseline in Early Treatment Diabetic Retinopathy Study (ETDRS) DRSS Score at Week 54 and Week 96 Baseline, Week 54 and Week 96 Severity of Diabetic retinopathy was evaluated using the ETDRS DRSS score assessed by the Central Reading Center based on color fundus photography images in the study eye. When the ETDRS-DR severities were evaluable, they were categorized on the original scale with scores varying from 10 (DR absent) to 85 (very advanced PDR). All DRSS values were then converted into a 12-level scale, allowing the derivation of the ≥2-step and ≥3-step change from baseline for each post-baseline assessment".
A lower score represents better functioning.Number and Percentage of Subjects Developing Vision-threatening Complications Associated With Diabetic Retinopathy up to Week 54 and up to Week 96 up to Week 54 and up to Week 96 The vision-threatening complications associated with Diabetic retinopathy (DR) are defined as any event of the following list occurring in the study eye at any time point after Baseline:
* Center-involved Diabetic macular edema (CI-DME) as defined as Central sub-field thickness (CSFT) ≥280 µm according to Central reading center (CRC) evaluation of Optical coherent tomography (OCT) image
* Retinal detachment
* Vitreous hemorrhage
* Neovascular glaucoma, iris/ anterior chamber angle neovascularization
* Vitrectomy for DR complicationsOcular AEs (>= 2% in Any Treatment Arm) by Preferred Term for the Study Eye Adverse events are reported from first dose of study treatment up to Week 90, plus approximately 6 weeks post-treatment, up to a maximum timeframe of approximately 96 weeks. An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a subject or clinical investigation subject.
AEs that started after alternative diabetic retinopathy treatment/relevant diabetic macular edema treatment in the study eye are censored.Non-ocular AEs (≥ 2% in Any Treatment Arm) by Preferred Term Adverse events are reported from first dose of study treatment up to Week 90, plus approximately 6 weeks post-treatment, up to a maximum timeframe of approximately 96 weeks. An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a subject or clinical investigation subject.
AEs that started after alternative diabetic retinopathy treatment/relevant diabetic macular edema treatment in the study eye are censored.
Trial Locations
- Locations (41)
Retina Associates SW
🇺🇸Tucson, Arizona, United States
Retina- Vitreous Assoc Medical Group
🇺🇸Beverly Hills, California, United States
Retina Consultants of Orange County
🇺🇸Fullerton, California, United States
Salehi Retina Institute
🇺🇸Huntington Beach, California, United States
Retina Consultants of Southern California
🇺🇸Redlands, California, United States
Premiere Practice Management LLC
🇺🇸Torrance, California, United States
Lundquist Inst BioMed at Harbor
🇺🇸Torrance, California, United States
Miramar Eye Specialists
🇺🇸Ventura, California, United States
Advanced Research LLC
🇺🇸Deerfield Beach, Florida, United States
Rand Eye Institute
🇺🇸Deerfield Beach, Florida, United States
Scroll for more (31 remaining)Retina Associates SW🇺🇸Tucson, Arizona, United States