Head to Head Study of Anti-VEGF Treatment. (RELIANCE)

An Exploratory Single Site, Open Label, Randomized, Controlled Study to Evaluate Plasma Vascular Endothelial Growth Factor Levels After Intravitreal Injection of Ranibizumab (Lucentis) and Conbercept (Langmu) for nAMD

An exploratory single site, open label, randomized, controlled study evaluated plasma vascular endothelial growth factor levels after intravitreal injection of ranibizumab (Lucentis) and conbercept (Langmu) for neovascular age-related macular degeneration

Study Overview

• Status: Completed
• Conditions: Age-related Macular Degeneration
• Intervention / Treatment: Drug: ranibizumab; Drug: Conbercept

Detailed Description

This prospective, randomized, open label study enrolled patients with neovascular AMD who were naïve to anti-VEGF therapy or have not received intravitreal anti-VEGF therapy for the previous 3 months. Patients were randomized in two treatment arms for 3 months:

• Study arm 1: Three monthly injections of 0.5mg Ranibizumab
• Study arm 2: Three monthly injections of 0.5mg Conbercept Blood sample (plasma/serum) was collected at baseline (pre-dose), 3h post-injections and days 1, 3, 7 and 28, following doses 1 and 3 for PK and systemic VEGF analysis. The lab staff was blinded for treatment allocation.

Plasma VEGF concentration was measured by a blinded laboratory using Quantikine® ELISA kits. Serum ranibizumab and conbercept concentration will be determined using validated ELISA assay.

The study was divided into 2 stages: the 1st initial feasibility stage with 6 patients per arm (12 patients in total) to verify SD for sample size justification and 2nd stage to confirm the findings with justified sample size.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Written informed consent must be obtained before any assessment is performed.
2. Male or female patient ≥ 50 years of age.
3. Subfoveal CNV secondary to nAMD.
4. BCVA score must be between 73 and 24 letters as measured by ETDRS chart

Exclusion Criteria:

For both eyes

1. Any active periocular or ocular infection or inflammation
2. Uncontrolled glaucoma
3. Neovascularization of the iris or neovascular glaucoma. For study eye
4. Choroidal neovascularization of any other cause than wet AMD
5. Ocular disorders present that may confound interpretation of study results,
6. Previous treatment with verteporfin PDT (Visudyne®), external-beam radiation therapy, focal laser photocoagulation, vitrectomy, submacular surgery, or transpupillary thermotherapy.
7. Structural damage within 0.5 disc diameter of the center of the macula
8. Atrophy or fibrosis involving the center of the fovea.
9. Inability of obtaining required lab report. Ocular medical history
10. History of intravitreal injection with any anti-VEGF drugs within 3 months. Exclusion criteria for systemic medical conditions and treatment
11. Any type of systemic disease or its treatment
12. Any patients diagnosed with tumor.
13. Stroke or myocardial infarction less than 3 months.
14. Known hypersensitivity to indocyanine green, fluorescein, or any component of the investigational drug formulation.
15. Use of any systemic anti-VEGF drugs within 6 months. Exclusion criteria for patient
16. Patients who have participated in other investigational drug study within 60 days.
17. Pregnant or nursing (lactating) women.
18. Inability to comply with study or follow-up procedures.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ranibizumab 0.5 mg; Three monthly injections of 0.5mg Ranibizumab	Drug: ranibizumab; Other Names: Lucentis
Active Comparator: Conbercept 0.5 mg; Three monthly injections of 0.5mg Conbercept	Drug: Conbercept; Other Names: Langmu

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Plasma Vascular Endothelial Growth Factor (VEGF) Concentration After First Injection at Visit 5 (Day 8 +/- 1 Day)	Change from baseline in plasma Vascular endothelial growth factor (VEGF) concentration after first injection at Visit 5 (Day 8 +/- 1 day).Blood sample was collected for systemic VEGF. VEGF was measured by a blinded laboratory using ELISA kits.	Baseline, Visit 5 (Day 8 +/- 1 day)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Plasma Vascular Endothelial Growth Factor (VEGF) Concentration After Third Injection at Visit 10 (Day 67 +/- 1 Day)	Change from baseline in plasma Vascular endothelial growth factor (VEGF) concentration after third injection at Visit 10 (Day 67 +/- 1 day). Blood sample was collected for systemic VEGF. VEGF will be measured by a blinded laboratory using ELISA kits.	Baseline, Visit 10 (Day 67 +/- 1 day)
Plasma VEGF Concentration at Baseline, Visit 2, 3, 4, 5, 6 After 1st Injection	Blood sample will be collected for systemic VEGF. VEGF will be measured by a blinded laboratory using ELISA kits. Baseline, Visit Visit 2, 3, 4, 5, 6 after 1st injection	Baseline, Visit 2, 3, 4, 5, 6
Plasma VEGF Concentration at Baseline, Visit 7, 8, 9, 10, 11 After 3rd Injection	Blood sample will be collected for systemic VEGF. VEGF will be measured by a blinded laboratory using ELISA kits. Baseline, Visit 7, 8, 9, 10, 11 after 3rd injection	Baseline, Visit 7, 8, 9, 10, 11

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): January 13, 2016
• Primary Completion (Actual): July 9, 2016
• Study Completion (Actual): July 9, 2016

Study Registration Dates

• First Submitted: July 30, 2015
• First Submitted That Met QC Criteria: October 13, 2015
• First Posted (Estimate): October 16, 2015

Study Record Updates

• Last Update Posted (Actual): November 30, 2017
• Last Update Submitted That Met QC Criteria: July 9, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: PK; Age-related macular degeneration,; ranibizumab,; conbercept,; plasma VEGF
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Physiological Effects of Drugs; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Ranibizumab
• Other Study ID Numbers: CRFB002ACN07

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

IPD 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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No