臨床研究等提出・公開システム

A 96-week, two-arm, randomized, single-masked, multicenter, phase III study assessing the efficacy and safety of brolucizumab 6 mg compared to panretinal photocoagulation laser in patients with proliferative diabetic retinopathy

Study of Efficacy and Safety of Brolucizumab Versus Panretinal Photocoagulation Laser in Patients With Proliferative Diabetic Retinopathy

689

In the Brolucizumab 6 mg group (N=347), the mean age was 53.2 years (standard deviation: 11.88). There were 203 males and 144 females. The main racial groups were White (166 participants) and Asian (157 participants). In the Panretinal photocoagulation (PRP) group (N=342), the mean age was 54.7 years (standard deviation: 10.83). There were 210 males and 132 females. The main racial groups were White (169 participants) and Asian (148 participants).

In the Brolucizumab 6 mg group, 347 participants were enrolled, 301 completed the study, and discontinuation was reported for 46 participants. The main reasons for discontinuation were withdrawal by the participant (n=20) and loss to follow-up (n=11). In the PRP group, 342 participants were enrolled, 287 completed the study, and discontinuation was reported for 55 participants. The main reasons for discontinuation were withdrawal by the participant (n=20) and loss to follow-up (n=13). The majority of subjects in the brolucizumab 6 mg group received 3 x q6w doses in the loading phase, followed by a maintenance treatment of 3 x q12w doses up to Week 54 and q18w/q24w doses during the second year.

The number of subjects who died (96 weeks) was 8 in the brolucizumab 6 mg group and 9 in the PRP group. The number of subjects with serious adverse events (96 weeks) was 96 in the brolucizumab 6 mg group and 105 in the PRP group. The incidence of adverse events in the treated eye (96 weeks) was 43.80% (152/347 subjects) in the brolucizumab 6 mg group and 58.19% (199/342 subjects) in the PRP group. The most common event was vitreous haemorrhage in both groups, 10.95% (38/347 subjects) in the brolucizumab 6 mg group and 24.27% (83/342 subjects) in the PRP group. The incidence of non-ocular adverse events (96 weeks) was 65.13% (226/347 subjects) in the brolucizumab 6 mg group and 63.45% (217/342 subjects) in the PRP group. The most common event was COVID-19 in both groups, 12.68% (44/347 subjects) in the brolucizumab 6 mg group and 13.74% (47/342 subjects) in the PRP group.

The primary endpoint of this study was the change from baseline to Week 54 in best-corrected visual acuity (BCVA) in the study eye. BCVA was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart, and subjects with an ETDRS letter score of >=34 letters (Snellen equivalent of 20/200) in the study eye at screening/baseline were included in the analysis. Missing values were imputed using the Last Observation Carried Forward (LOCF) method. The analysis population was the Full Analysis Set - Last Observation Carried Forward (FAS-LOCF). The assessment time points were baseline and Week 54. The number of subjects included in the primary endpoint analysis was 342 in the Brolucizumab 6 mg group and 337 in the PRP group. At Week 54, the change from baseline in BCVA (least-squares mean +/- standard error) was 0.2 +/- 0.72 letters in the Brolucizumab 6 mg group and -4.2 +/- 0.73 letters in the PRP group. Statistical analysis was performed using analysis of covariance (ANCOVA) as a non-inferiority test. The least-squares mean difference in BCVA change between the Brolucizumab 6 mg group and the PRP group was 4.4 letters, with a standard error of 1.03 and a two-sided 95% confidence interval of 2.4 to 6.4. The non-inferiority margin was set at 4 letters, and the P value was <0.001. Year 2 (Week 96) outcomes confirmed the results observed in Year 1 (Week 54). At Week 96, the Least Square Mean difference in BCVA from baseline between brolucizumab and PRP was +5.8 letters, despite fewer injections in Year 2.

Non-inferiority of brolucizumab 6 mg to PRP was demonstrated on visual acuity for the primary endpoint as measured by change from baseline in best corrected visual acuity (BCVA) at Week 54. In addition, brolucizumab 6mg also demonstrated the superiority over PRP in terms of BCVA for the primary endpoint. Overall, the safety profile of brolucizumab 6 mg was established up to 2 years, showing comparable results with PRP. No new ocular or non-ocular safety signals were identified.

No

https://jrct.mhlw.go.jp/latest-detail/jRCT2031200194

Maruyama Hideki

Novartis Pharma. K.K.

Toranomon Hills Mori Tower 23-1, Toranomon 1-chome Minato-ku, Tokyo 105-6333, Japan

rinshoshiken.toroku@novartis.com

Maruyama Hideki

Novartis Pharma. K.K.

Toranomon Hills Mori Tower 23-1, Toranomon 1-chome Minato-ku, Tokyo 105-6333, Japan

+81-120-003-293

rinshoshiken.toroku@novartis.com

Complete

Nov. 30, 2020

Interventional

randomized controlled trial

single blind

active control

parallel assignment

treatment purpose

- 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"

Both

Proliferative diabetic retinopathy

Experimental: Brolucizumab Arm (Intra-vitreal injection), Active Comparator: Panretinal photocoagulation laser Arm (laser)

proliferative diabetic retinophathy, retinal neovascularization, anti-VEGF, brolucizumab, intravitreal injection, panretinal photocoagulation

Change from Baseline in BCVA, to demonstrate that brolucizumab is non-inferior to PRP with respect to the change from Baseline in visual acuity at Week 54

+81-285-58-7195

July. 20, 2020

Argentina/Australia/Brazil/Canada/Chile/China/India/Mexico/Philippines/Rep Korea/Russia/Taiwan/Turkey/USA