Non Infectious Uveitis
Conditions
Brief summary
This is a Phase III study to assess the efficacy and safety of DE-109 440 µg every 2 months in subjects with active, non-infectious uveitis of the posterior segment of the eye (NIU-PS). There is a 6-month, single-arm, open-label period after completion of the 6-month double- masked, controlled period allows the evaluation of the efficacy and safety of intravitreal injection of DE-109 440 µg every 2 months for longer duration than appropriate for a placebo or sham control.
Interventions
DRUGDE-109 Intravitreal Injections
440 ug of DE-109 Injectable Solution
OTHERSham Procedure
The sham procedure mimics an intravitreal injection without penetrating the eye.
DRUGDE-109 Intravitreal Injections (Open Label)
After double-masked treatment period (injections every 2 months), eligible subjects would enter the open-labeled period and had DE-109 440 ug injections every 2 months (Month 6, Month 8, and Month 10)
Sponsors
Santen Inc.
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
Non-Infectious Active Uveitis of the Posterior Segment
Exclusion criteria
Females who are pregnant, nursing, or planning a pregnancy Confirmed or suspected infectious uveitis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Vitreous Haze (VH) of Zero Response at Month 5 | Month 5 | Vitreous Haze (VH) was assessed during slit-lamp biomicroscopy and scored using the modified Standardized Uveitis Nomenclature (SUN) scale as follows: * Score = 0: No inflammation * Score = 0.5+: Trace inflammation (slight blurring if the optic disc margins and/or loss of nerve fiber layer reflex) * Score = 1+: Mild blurring of the retinal vessels and optic nerve * Score = 1.5+: Optic nerve had and posterior retina view obstruction greater than 1+ but less than 2+ * Score = 2+: Moderate blurring of the optic nerve head * Score = 3+: Marked blurring of the optic nerve head * Score = 4+: Optic nerve head not visible VH 0 response (resolution of inflammation) is defined as a VH score of 0 in the study eye at a specified follow up visit based on the modified SUN scale. The response as a percentage is calculated as the proportion of study eyes which achieved a VH score of zero at Month 5 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Composite Score at Month 3 and Month 5 | Month 3, Month 5 | Composite score scale is defined as follows. Each study eye was assigned one of the following scores: * Score = 3 if a study eye achieved Vitreous Haze (VH) score of 0 at the specified visit without taking any rescue therapies that could affect VH score prior to the specified visit. * Score = 2 if a study eye had at least improved (decreased) by 2 units (i.e., 2+ to 0, 3+ to 1+, or 4+ to 2+) in VH (compared to baseline) at the specified visit without taking any rescue therapies that could affect VH score prior to the specified visit. * Score = 1 if a study eye achieved VH score of 0.5+ at the specified visit without taking any rescue therapies that could affect VH score prior to the specified visit. * Score = -1 if a study eye got rescued due to worsening of uveitis or discontinued from the study due to lack of efficacy or due to adverse event prior to the specified visit. * Score = 0 if otherwise |
| Vitreous Haze (VH) of Zero Response at Month 3 | Month 3 | Vitreous Haze (VH) was assessed during slit-lamp biomicroscopy and scored using the modified Standardized Uveitis Nomenclature (SUN) scale as follows: * Score = 0: No inflammation * Score = 0.5+: Trace inflammation (slight blurring if the optic disc margins and/or loss of nerve fiber layer reflex) * Score = 1+: Mild blurring of the retinal vessels and optic nerve * Score = 1.5+: Optic nerve had and posterior retina view obstruction greater than 1+ but less than 2+ * Score = 2+: Moderate blurring of the optic nerve head * Score = 3+: Marked blurring of the optic nerve head * Score = 4+: Optic nerve head not visible VH 0 response (resolution of inflammation) is defined as a VH score of 0 in the study eye at a specified follow up visit based on the modified SUN scale. The response as a percentage is calculated as the proportion of study eyes which achieved a VH score of zero at Month 3. |
Countries
Argentina, India, Italy, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Test Arm: DE-109 Injectable Solution Intravitreal injection of DE-109 440 µg in the study eye(s) every 2 months (Day 1, Month 2, and Month 4).
DE-109 Intravitreal Injections: 440 ug of DE-109 Injectable Solution | 57 |
| Control Arm: Sham Procedure Sham procedure administered to the study eye(s) every 2 months (Day 1, Month 2, and Month 4). The sham procedure mimics an intravitreal injection without penetrating the eye.
Sham Procedure: The sham procedure mimics an intravitreal injection without penetrating the eye. | 59 |
| Dummy Arm: DE-109 Injectable Solution Dummy Arm: Intravitreal injection of DE-109 at an undisclosed, fixed dose (within the range of 44 µg to 880 µg) in the study eye(s) every 2 months (Day 1, Month 2, and Month 4). This study arm (which has the same route of administration and frequency as the test arm).
DE-109 Intravitreal Injections: Undisclosed Fixed Dose of DE-109 Injectable Solution (range of 44 ug to 880 ug) | 29 |
| Total | 145 |
Baseline characteristics
| Characteristic | Test Arm: DE-109 Injectable Solution | Control Arm: Sham Procedure | Dummy Arm: DE-109 Injectable Solution | Total |
|---|---|---|---|---|
| Age, Continuous | 46.8 years STANDARD_DEVIATION 17.26 | 46.2 years STANDARD_DEVIATION 14.4 | 47.0 years STANDARD_DEVIATION 14.27 | 46.6 years STANDARD_DEVIATION 15.46 |
| Age, Customized <65 | 47 Participants | 52 Participants | 27 Participants | 126 Participants |
| Age, Customized >= 65 years | 10 Participants | 7 Participants | 2 Participants | 19 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 19 Participants | 18 Participants | 11 Participants | 48 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants | 7 Participants | 6 Participants | 21 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 29 Participants | 33 Participants | 12 Participants | 74 Participants |
| Region of Enrollment Argentina | 12 participants | 9 participants | 3 participants | 24 participants |
| Region of Enrollment India | 18 participants | 16 participants | 11 participants | 45 participants |
| Region of Enrollment Italy | 1 participants | 3 participants | 1 participants | 5 participants |
| Region of Enrollment United States | 26 participants | 31 participants | 14 participants | 71 participants |
| Sex: Female, Male Female | 36 Participants | 35 Participants | 14 Participants | 85 Participants |
| Sex: Female, Male Male | 21 Participants | 24 Participants | 15 Participants | 60 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 57 | 0 / 59 | 0 / 29 | 0 / 42 | 0 / 40 | 0 / 21 |
| other Total, other adverse events | 47 / 57 | 45 / 59 | 22 / 29 | 31 / 42 | 25 / 40 | 8 / 21 |
| serious Total, serious adverse events | 7 / 57 | 3 / 59 | 5 / 29 | 3 / 42 | 1 / 40 | 0 / 21 |
Outcome results
Primary
Vitreous Haze (VH) of Zero Response at Month 5
Vitreous Haze (VH) was assessed during slit-lamp biomicroscopy and scored using the modified Standardized Uveitis Nomenclature (SUN) scale as follows: * Score = 0: No inflammation * Score = 0.5+: Trace inflammation (slight blurring if the optic disc margins and/or loss of nerve fiber layer reflex) * Score = 1+: Mild blurring of the retinal vessels and optic nerve * Score = 1.5+: Optic nerve had and posterior retina view obstruction greater than 1+ but less than 2+ * Score = 2+: Moderate blurring of the optic nerve head * Score = 3+: Marked blurring of the optic nerve head * Score = 4+: Optic nerve head not visible VH 0 response (resolution of inflammation) is defined as a VH score of 0 in the study eye at a specified follow up visit based on the modified SUN scale. The response as a percentage is calculated as the proportion of study eyes which achieved a VH score of zero at Month 5
Time frame: Month 5
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Test Arm: DE-109 Injectable Solution | Vitreous Haze (VH) of Zero Response at Month 5 | 15.7 percentage response of study eyes |
| Control Arm: Sham Procedure | Vitreous Haze (VH) of Zero Response at Month 5 | 12.2 percentage response of study eyes |
| Dummy Arm: DE-109 Injectable Solution | Vitreous Haze (VH) of Zero Response at Month 5 | 28.7 percentage response of study eyes |
Secondary
Mean Composite Score at Month 3 and Month 5
Composite score scale is defined as follows. Each study eye was assigned one of the following scores: * Score = 3 if a study eye achieved Vitreous Haze (VH) score of 0 at the specified visit without taking any rescue therapies that could affect VH score prior to the specified visit. * Score = 2 if a study eye had at least improved (decreased) by 2 units (i.e., 2+ to 0, 3+ to 1+, or 4+ to 2+) in VH (compared to baseline) at the specified visit without taking any rescue therapies that could affect VH score prior to the specified visit. * Score = 1 if a study eye achieved VH score of 0.5+ at the specified visit without taking any rescue therapies that could affect VH score prior to the specified visit. * Score = -1 if a study eye got rescued due to worsening of uveitis or discontinued from the study due to lack of efficacy or due to adverse event prior to the specified visit. * Score = 0 if otherwise
Time frame: Month 3, Month 5
Population: Full Analysis Set. The number of overall participants analyzed is consistent with data here and other parts of the record. Data represented in all records are for whole participants. Subjects with two study eyes had the composite score as the average score of both eyes.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Test Arm: DE-109 Injectable Solution | Mean Composite Score at Month 3 and Month 5 | Month 3 | 0.4 score on a scale | Standard Deviation 1.1 |
| Test Arm: DE-109 Injectable Solution | Mean Composite Score at Month 3 and Month 5 | Month 5 | 0.3 score on a scale | Standard Deviation 1.11 |
| Control Arm: Sham Procedure | Mean Composite Score at Month 3 and Month 5 | Month 3 | 0.3 score on a scale | Standard Deviation 0.8 |
| Control Arm: Sham Procedure | Mean Composite Score at Month 3 and Month 5 | Month 5 | 0.3 score on a scale | Standard Deviation 1.04 |
| Dummy Arm: DE-109 Injectable Solution | Mean Composite Score at Month 3 and Month 5 | Month 3 | 0.4 score on a scale | Standard Deviation 0.98 |
| Dummy Arm: DE-109 Injectable Solution | Mean Composite Score at Month 3 and Month 5 | Month 5 | 0.6 score on a scale | Standard Deviation 1.31 |
Secondary
Vitreous Haze (VH) of Zero Response at Month 3
Vitreous Haze (VH) was assessed during slit-lamp biomicroscopy and scored using the modified Standardized Uveitis Nomenclature (SUN) scale as follows: * Score = 0: No inflammation * Score = 0.5+: Trace inflammation (slight blurring if the optic disc margins and/or loss of nerve fiber layer reflex) * Score = 1+: Mild blurring of the retinal vessels and optic nerve * Score = 1.5+: Optic nerve had and posterior retina view obstruction greater than 1+ but less than 2+ * Score = 2+: Moderate blurring of the optic nerve head * Score = 3+: Marked blurring of the optic nerve head * Score = 4+: Optic nerve head not visible VH 0 response (resolution of inflammation) is defined as a VH score of 0 in the study eye at a specified follow up visit based on the modified SUN scale. The response as a percentage is calculated as the proportion of study eyes which achieved a VH score of zero at Month 3.
Time frame: Month 3
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Test Arm: DE-109 Injectable Solution | Vitreous Haze (VH) of Zero Response at Month 3 | 14.7 percentage response of study eyes |
| Control Arm: Sham Procedure | Vitreous Haze (VH) of Zero Response at Month 3 | 5.5 percentage response of study eyes |
| Dummy Arm: DE-109 Injectable Solution | Vitreous Haze (VH) of Zero Response at Month 3 | 15.4 percentage response of study eyes |