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

Sponsor

ThromboGenics (Industry)

Overall Status

Completed

CT.gov ID

NCT03071068

Collaborator

(none)

Enrollment

Locations

Arms

15.3

Actual Duration (Months)

3.8

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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).

Condition or Disease	Intervention/Treatment	Phase
Diabetic Retinopathy Macular Edema	Drug: Anti-PlGF recombinant monoclonal antibody, 4mg dose Drug: Anti-PlGF recombinant monoclonal antibody, 8mg dose	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

49 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Participant)

Primary Purpose:

Treatment

Official Title:

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)

Actual Study Start Date :

Dec 22, 2016

Actual Primary Completion Date :

Apr 1, 2018

Actual Study Completion Date :

Apr 1, 2018

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	City	Country	Postal Code
1	Brno	Czechia	625 00
2	Hradec Kralove	Czechia	500 05
3	Praha 10	Czechia	100 34
4	Praha 8	Czechia	180 00
5	Budapest	Hungary	1083
6	Budapest	Hungary	1133
7	Debrecen	Hungary	4032
8	Pecs	Hungary	7621
9	Szeged	Hungary	6720
10	Bratislava	Slovakia	826 06
11	Bratislava	Slovakia	851 07
12	Trenčín	Slovakia	911 71
13	Zilina	Slovakia	012 07