A Study to Evaluate the Safety and Efficacy of THR-317 for the Treatment of Diabetic Macular Oedema (DME)

A Phase 2, Single-masked, Multicentre Study to Evaluate the Safety and Efficacy of 2 Dose Levels of THR-317 for the Treatment of Diabetic Macular Oedema (DME)

This study is conducted to evaluate the safety of THR-317 when administered intravitreally and to assess the compound's efficacy in improving best-corrected visual acuity (BCVA) and reducing central subfield thickness (CST) in subjects with centre-involved diabetic macular oedema (DME).

Study Overview

• Status: Completed
• Conditions: Diabetic Retinopathy; Macular Edema
• Intervention / Treatment: Drug: Anti-PlGF recombinant monoclonal antibody, 4mg dose; Drug: Anti-PlGF recombinant monoclonal antibody, 8mg dose

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 2

Contacts and Locations

Study Locations

• Czechia
  • Brno, Czechia, 625 00
  • Hradec Kralove, Czechia, 500 05
  • Praha 10, Czechia, 100 34
  • Praha 8, Czechia, 180 00
• Hungary
  • Budapest, Hungary, 1083
  • Budapest, Hungary, 1133
  • Debrecen, Hungary, 4032
  • Pecs, Hungary, 7621
  • Szeged, Hungary, 6720
• Slovakia
  • Bratislava, Slovakia, 826 06
  • Bratislava, Slovakia, 851 07
  • Trenčín, Slovakia, 911 71
  • Zilina, Slovakia, 012 07

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• Male or female aged 18 years or older
• Type 1 or type 2 diabetes
• Centre-involved DME with CST ≥ 340µm on Spectralis SD-OCT or ≥ 320µm on non-Spectralis SD OCT, in the study eye
• Reduced vision primarily due to DME, with BCVA between 72 and 23 ETDRS letters read at 4 meters (20/40 and 20/320 Snellen equivalent) in the study eye
• Anti-vascular endothelial growth factor (anti-VEGF) treatment naïve study eye or poor response to prior anti-VEGF treatment in the study eye
• Non-proliferative diabetic retinopathy, or stable proliferative diabetic retinopathy without neovacularisation at the disc
• Written informed consent obtained from the subject prior to screening procedures

Exclusion criteria:

• Concurrent disease in the study eye, other than DME, that could compromise BCVA, require medical or surgical intervention during the study period or could confound interpretation of the results
• Previous treatments / procedures in the study eyes as follows, or their planned use during the THR-317 treatment period for up to 30 days after the last injection: panretinal or focal / grid laser photocoagulation [3 months], anti-VEGF treatment [any time for anti-VEGF naïve subjects; 4 weeks for subjects with a poor response to anti-VEGF treatment], intra-ocular or peri-ocular corticosteroids [4 months], steroid implant [any time], intra-ocular surgery [3 months], vitrectomy [any time]
• Any active ocular / intra-ocular infection or inflammation in either eye
• Aphakic study eye
• Untreated diabetes
• Glycated haemoglobin A (HbA1c) > 12%
• Uncontrolled hypertension in the opinion of the Investigator
• Pregnant or lactating female or female of child-bearing potential not utilising an adequate form of contraception or male of reproductive potential not utilising contraception suggesting lens / zonular instability

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: THR-317 4mg; anti-PlGF recombinant monoclonal antibody, 4mg dose	Drug: Anti-PlGF recombinant monoclonal antibody, 4mg dose; 3 intravitreal injections of THR-317 4mg approximately 1 month apart
Experimental: THR-317 8mg; anti-PlGF recombinant monoclonal antibody, 8mg dose	Drug: Anti-PlGF recombinant monoclonal antibody, 8mg dose; 3 intravitreal injections of THR-317 8mg approximately 1 month apart

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of acute (up to the 7-day follow-up visit) ocular (serious) adverse events ([S]AEs) in the study eye, after each injection and across injections per subject	up to the 7-day follow-up visit after each injection

Secondary Outcome Measures

Outcome Measure	Time Frame
Incidence of systemic and ocular (S)AEs up to the 30-day follow-up visit, after each injection and across injections per subject	up to the 30-day follow-up visit after each injection
Incidence of systemic and ocular (S)AEs from first injection up to Day 90 and up to Day 150	From day 0 to day 150
Proportion of subjects withdrawn from repeat injection and reason for withdrawal	At day 30 and at day 60
Proportion of subjects with a loss of ≥ 15, ≥ 10 or ≥ 5 ETDRS letters in BCVA from baseline by study visit	Up to day 150
Proportion of subjects with an acute loss (up to the 7-day follow-up visit) of ≥ 15, ≥ 10 or ≥ 5 ETDRS letters in BCVA after each injection	Up to 7-day follow-up visit after each injection
Proportion of subjects with a ≥ 15 ETDRS letters gain in BCVA from baseline or ≥ 83 ETDRS letters, by study visit	Up to day 150
Mean change from baseline in BCVA, by study visit	Up to day 150
Mean change from baseline in CST, by study visit, based on spectral domain optical coherence tomography (SD-OCT), as assessed by the central reading centre (CRC)	Up to day 150

Collaborators and Investigators

• Sponsor: ThromboGenics
• Investigators: Study Director: Clinical Department, ThromboGenics

Study record dates

Study Major Dates

• Study Start (Actual): December 22, 2016
• Primary Completion (Actual): April 1, 2018
• Study Completion (Actual): April 1, 2018

Study Registration Dates

• First Submitted: February 21, 2017
• First Submitted That Met QC Criteria: February 28, 2017
• First Posted (Actual): March 6, 2017

Study Record Updates

• Last Update Posted (Actual): April 17, 2018
• Last Update Submitted That Met QC Criteria: April 16, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Eye Diseases; Endocrine System Diseases; Diabetic Angiopathies; Diabetes Complications; Diabetes Mellitus; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Diabetic Retinopathy; Macular Edema; Edema; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Antineoplastic Agents, Immunological
• Other Study ID Numbers: THR-317-001; 2016-002100-25 (EudraCT Number)