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A Study to Evaluate THR-687 Treatment for Diabetic Macular Oedema. (INTEGRAL)

Primary Purpose

Diabetes Mellitus, Diabetic Retinopathy, Diabetic Macular Edema

Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
THR-687 dose level 1
THR-687 dose level 2
THR-687 selected dose level
Aflibercept
Sponsored by
Oxurion
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diabetes Mellitus

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Salehi Retina Institute Inc.
  • California Eye Specialists Medical Group, Inc.
  • Retinal Consultants Medical Group
  • Retina Consultants of Southern Colorado, P.C.
  • Retina Associates, Ltd
  • University Retina and macula Associates, PC
  • Cumberland Valley Retina Consultants
  • Sierra Eye Associates
  • Retina Vitreous Surgeons of Central New York, PC
  • Tulsa Retina Consultants
  • Eye Care Specialists
  • Tennessee Retina, PC
  • Austin Research Center of Retina
  • Retina Consultants of Texas
  • Valley Retina Institute, P.A.
  • Medical Center Ophthalmology Associates
  • Retina Center of Texas
  • Strategic Clinical Research Group
  • Eye Clinic Dr Krista Turman
  • Silmalaser OU
  • Ganglion Medical Center
  • Szegedi Tudományegyetem
  • Pauls Stradins Clinical University Hospital
  • Riga East Clinical University Hospital
  • Vilnius University Hospital Santaros klinikos

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Experimental

Experimental

Active Comparator

Experimental

Active Comparator

Arm Label

Part A, THR-687 1.2 mg

Part A, THR-687 2.0mg

Part B, treatment naïve subjects, THR-687 selected dose level

Part B, treatment naïve subjects, aflibercept 2.0mg

Part B, previously treated subjects, THR-687 selected dose level

Part B, previously treated subjects, aflibercept 2.0mg

Arm Description

Due to the discontinuation of the study after Part A, the dose level for Part B has not been selected

Due to the discontinuation of the study after Part A, the dose level for Part B has not been selected

Outcomes

Primary Outcome Measures

Change From Baseline in BCVA ETDRS Letter Score, at Month 3, in Treatment-naïve Subjects in Part B of the Study

Secondary Outcome Measures

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
Change From Baseline in BCVA ETDRS Letter Score, by Study Visit, in Treatment-naïve Subjects in Part B of the Study
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
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.

Full Information

First Posted
September 8, 2021
Last Updated
July 25, 2023
Sponsor
Oxurion
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1. Study Identification

Unique Protocol Identification Number
NCT05063734
Brief Title
A Study to Evaluate THR-687 Treatment for Diabetic Macular Oedema.
Acronym
INTEGRAL
Official Title
A Phase 2, Randomised, Multicentre Study to Assess the Dose Level of Multiple THR-687 Injections and to Evaluate the Efficacy and Safety of THR-687 Versus Aflibercept for the Treatment of Diabetic Macular Oedema (DME)
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Terminated
Why Stopped
Based on data obtained in Part A, there was insufficient evidence of efficacy on the key outcome measures. As a result, the study was not advanced to Part B.
Study Start Date
August 27, 2021 (Actual)
Primary Completion Date
June 29, 2022 (Actual)
Study Completion Date
June 29, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Oxurion

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus, Diabetic Retinopathy, Diabetic Macular Edema

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
16 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Part A, THR-687 1.2 mg
Arm Type
Experimental
Arm Title
Part A, THR-687 2.0mg
Arm Type
Experimental
Arm Title
Part B, treatment naïve subjects, THR-687 selected dose level
Arm Type
Experimental
Arm Description
Due to the discontinuation of the study after Part A, the dose level for Part B has not been selected
Arm Title
Part B, treatment naïve subjects, aflibercept 2.0mg
Arm Type
Active Comparator
Arm Title
Part B, previously treated subjects, THR-687 selected dose level
Arm Type
Experimental
Arm Description
Due to the discontinuation of the study after Part A, the dose level for Part B has not been selected
Arm Title
Part B, previously treated subjects, aflibercept 2.0mg
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
THR-687 dose level 1
Intervention Description
3 intravitreal injections of THR-687 dose level 1, 1 month apart
Intervention Type
Drug
Intervention Name(s)
THR-687 dose level 2
Intervention Description
3 intravitreal injections of THR-687 dose level 2, 1 month apart
Intervention Type
Drug
Intervention Name(s)
THR-687 selected dose level
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Aflibercept
Other Intervention Name(s)
Eylea®
Intervention Description
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.
Primary Outcome Measure Information:
Title
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
Secondary Outcome Measure Information:
Title
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
Title
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
Title
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
Title
Incidence of Ocular and Non-ocular Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description
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)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Department
Organizational Affiliation
Oxurion
Official's Role
Study Director
Facility Information:
Facility Name
Salehi Retina Institute Inc.
City
Huntington Beach
State/Province
California
ZIP/Postal Code
92647
Country
United States
Facility Name
California Eye Specialists Medical Group, Inc.
City
Pasadena
State/Province
California
ZIP/Postal Code
91107
Country
United States
Facility Name
Retinal Consultants Medical Group
City
Sacramento
State/Province
California
ZIP/Postal Code
95825
Country
United States
Facility Name
Retina Consultants of Southern Colorado, P.C.
City
Colorado Springs
State/Province
Colorado
ZIP/Postal Code
80909
Country
United States
Facility Name
Retina Associates, Ltd
City
Elmhurst
State/Province
Illinois
ZIP/Postal Code
60126
Country
United States
Facility Name
University Retina and macula Associates, PC
City
Oak Forest
State/Province
Illinois
ZIP/Postal Code
60452
Country
United States
Facility Name
Cumberland Valley Retina Consultants
City
Hagerstown
State/Province
Maryland
ZIP/Postal Code
21740
Country
United States
Facility Name
Sierra Eye Associates
City
Reno
State/Province
Nevada
ZIP/Postal Code
89502
Country
United States
Facility Name
Retina Vitreous Surgeons of Central New York, PC
City
Liverpool
State/Province
New York
ZIP/Postal Code
13088
Country
United States
Facility Name
Tulsa Retina Consultants
City
Tulsa
State/Province
Oklahoma
ZIP/Postal Code
74114
Country
United States
Facility Name
Eye Care Specialists
City
Kingston
State/Province
Pennsylvania
ZIP/Postal Code
18704
Country
United States
Facility Name
Tennessee Retina, PC
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
Austin Research Center of Retina
City
Austin
State/Province
Texas
ZIP/Postal Code
78705
Country
United States
Facility Name
Retina Consultants of Texas
City
Katy
State/Province
Texas
ZIP/Postal Code
77494
Country
United States
Facility Name
Valley Retina Institute, P.A.
City
McAllen
State/Province
Texas
ZIP/Postal Code
78503
Country
United States
Facility Name
Medical Center Ophthalmology Associates
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78240
Country
United States
Facility Name
Retina Center of Texas
City
Southlake
State/Province
Texas
ZIP/Postal Code
76092
Country
United States
Facility Name
Strategic Clinical Research Group
City
Willow Park
State/Province
Texas
ZIP/Postal Code
76087
Country
United States
Facility Name
Eye Clinic Dr Krista Turman
City
Tallinn
ZIP/Postal Code
11314
Country
Estonia
Facility Name
Silmalaser OU
City
Tallinn
ZIP/Postal Code
11412
Country
Estonia
Facility Name
Ganglion Medical Center
City
Pécs
ZIP/Postal Code
7621
Country
Hungary
Facility Name
Szegedi Tudományegyetem
City
Szeged
ZIP/Postal Code
6720
Country
Hungary
Facility Name
Pauls Stradins Clinical University Hospital
City
Riga
ZIP/Postal Code
LV-1002
Country
Latvia
Facility Name
Riga East Clinical University Hospital
City
Riga
ZIP/Postal Code
LV-1006
Country
Latvia
Facility Name
Vilnius University Hospital Santaros klinikos
City
Vilnius
ZIP/Postal Code
LT-08661
Country
Lithuania

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

A Study to Evaluate THR-687 Treatment for Diabetic Macular Oedema.

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