Diabetes Mellitus, Diabetic Macular Edema, Diabetic Retinopathy
Conditions
Brief summary
This study is conducted to select the THR-687 dose level (Part A of the study) and to assess the efficacy and safety of the selected dose level compared to aflibercept (Part B of the study).
Detailed description
In Part A, approximately 12 subjects are planned to be randomized (1:1 allocation) to THR-687 1.2mg and THR-687 2.0mg. In Part B, in the cohort of Treatment Naïve subjects are planned to be randomized (2:1 allocation) to THR-687 selected dose level from Part A and Aflibercept 2.0mg. In Part B, in the cohort of Previously Treated subjects are planned to be randomized (1:1 allocation) to THR-687 selected dose level from Part A and Aflibercept 2.0mg. All subjects in the study will receive study treatment in one selected study eye only.
Interventions
3 intravitreal injections of THR-687 dose level 1, 1 month apart
3 intravitreal injections of THR-687 dose level 2, 1 month apart
DRUGTHR-687 selected dose level
3 intravitreal injections of THR-687 selected dose level, 1 month apart, possibly followed by a 4th intravitreal injection with the same dose level of THR-687 at Month 3, or Month 4, or Month 5, if any of the PRN criteria are met.
DRUGAflibercept
3 intravitreal injections of aflibercept, 1 month apart, possibly followed by a 4th intravitreal injection with aflibercept at Month 3, or Month 4, or Month 5, if any of the PRN criteria are met.
Sponsors
Oxurion
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
The subjects in this study will be subjects with central-involved DME (CI-DME). Both treatment-naïve and previously treated subjects will be included. Inclusion Criteria: * Written informed consent obtained from the subject prior to screening procedures * Male or female aged 18 years or older at the time of signing the informed consent * Type 1 or type 2 diabetes * BCVA ETDRS letter score ≥ 39 in the study eye * CI-DME with CST of ≥ 300µm in men (or equivalent in women), measured from RPE to ILM inclusively, on SD-OCT, in the study eye * BCVA ETDRS letter score ≥ 34 in the fellow eye
Exclusion criteria
* Macular edema due to causes other than DME in the study eye * Concurrent disease in the study eye, other than DME, that could require medical or surgical intervention during the study period or could confound interpretation of the results * Any condition in the study eye that could confound the ability to detect the efficacy of the investigational medicinal product * Previous confounding medications / interventions, or their planned administration during the study * Presence of iris neovascularisation in the study eye * Uncontrolled glaucoma in the study eye * Previously received THR-687 or any other experimental therapy for DME, in either eye * Any active or suspected ocular or periocular infection, or active intraocular inflammation, in either eye * Untreated Diabetes * Glycated haemoglobin A (HbA1c) \> 12% * Uncontrolled hypertension
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change From Baseline in BCVA ETDRS Letter Score, at Month 3, in Treatment-naïve Subjects in Part B of the Study | At Month 3 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Weighted Average of the Change From Baseline in BCVA ETDRS Letter Score From Day 8 Through Month 3 Using the Trapezoidal Rule (AUC), in Treatment-naïve Subjects in Part B of the Study | at Month 3 | — |
| Change From Baseline in BCVA ETDRS Letter Score, by Study Visit, in Treatment-naïve Subjects in Part B of the Study | Up to Month 8 | — |
| Change From Baseline in Central Subfield Thickness (CST), Based on Spectral Domain Optical Coherence Tomography (SD-OCT), as Assessed by the Central Reading Center (CRC), by Study Visit, in Treatment-naïve Subjects in Part B of the Study | Up to Month 8 | — |
| Incidence of Ocular and Non-ocular Adverse Events (AEs) and Serious Adverse Events (SAEs) | Up to End of Study (Part A up to Month 6 and Part B up to Month 8) | Adverse Events will be reported from the date of Informed Consent until End of the Study visit (up to Month 6 in Part A and up to Month 8 in Part B) or at the early study discontinuation visit and will be coded using MedDRA. Adverse Events will be summarized by System Organ Class and Primary Term. Incidence by subject represents at least one occurrence of the Primary Term with an onset on or after the date of the first study treatment. If a subject has multiple occurrences of an adverse event (P-term), the subject is presented only once in the respective subject count. |
Countries
Estonia, Hungary, Latvia, Lithuania, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Part A, THR-687 1.2mg THR-687: 3 intravitreal injections of THR-687, 1 month apart | 7 |
| Part A, THR-687 2.0mg THR-687: 3 intravitreal injections of THR-687, 1 month apart | 9 |
| Total | 16 |
Baseline characteristics
| Characteristic | Part A, THR-687 2.0mg | Total | Part A, THR-687 1.2mg |
|---|---|---|---|
| Age, Continuous | 59.0 years STANDARD_DEVIATION 9.55 | 62.6 years STANDARD_DEVIATION 11.87 | 67.3 years STANDARD_DEVIATION 13.61 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 7 Participants | 13 Participants | 6 Participants |
| Sex: Female, Male Female | 3 Participants | 7 Participants | 4 Participants |
| Sex: Female, Male Male | 6 Participants | 9 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 9 |
| other Total, other adverse events | 4 / 7 | 6 / 9 |
| serious Total, serious adverse events | 0 / 7 | 0 / 9 |
Outcome results
Primary
Change From Baseline in BCVA ETDRS Letter Score, at Month 3, in Treatment-naïve Subjects in Part B of the Study
Time frame: At Month 3
Population: Part B of the study was not initiated due to insufficient evidence of efficacy based on the data obtained in Part A
Secondary
Change From Baseline in BCVA ETDRS Letter Score, by Study Visit, in Treatment-naïve Subjects in Part B of the Study
Time frame: Up to Month 8
Population: Part B of the study was not initiated due to insufficient evidence of efficacy based on the data obtained in Part A
Secondary
Change From Baseline in Central Subfield Thickness (CST), Based on Spectral Domain Optical Coherence Tomography (SD-OCT), as Assessed by the Central Reading Center (CRC), by Study Visit, in Treatment-naïve Subjects in Part B of the Study
Time frame: Up to Month 8
Population: Part B of the study was not initiated due to insufficient evidence of efficacy based on the data obtained in Part A
Secondary
Incidence of Ocular and Non-ocular Adverse Events (AEs) and Serious Adverse Events (SAEs)
Adverse Events will be reported from the date of Informed Consent until End of the Study visit (up to Month 6 in Part A and up to Month 8 in Part B) or at the early study discontinuation visit and will be coded using MedDRA. Adverse Events will be summarized by System Organ Class and Primary Term. Incidence by subject represents at least one occurrence of the Primary Term with an onset on or after the date of the first study treatment. If a subject has multiple occurrences of an adverse event (P-term), the subject is presented only once in the respective subject count.
Time frame: Up to End of Study (Part A up to Month 6 and Part B up to Month 8)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part B, Treatment naïve Subjects, THR-687 Selected Dose Level | Incidence of Ocular and Non-ocular Adverse Events (AEs) and Serious Adverse Events (SAEs) | 4 Participants |
| Part B, Treatment naïve Subjects, Aflibercept | Incidence of Ocular and Non-ocular Adverse Events (AEs) and Serious Adverse Events (SAEs) | 6 Participants |
Secondary
Weighted Average of the Change From Baseline in BCVA ETDRS Letter Score From Day 8 Through Month 3 Using the Trapezoidal Rule (AUC), in Treatment-naïve Subjects in Part B of the Study
Time frame: at Month 3
Population: Part B of the study was not initiated due to insufficient evidence of efficacy based on the data obtained in Part A