Diabetic Macular Edema
Conditions
Brief summary
This is a clinical study where patients with diabetes and a vision threatening eye condition called Diabetic Macular Edema receive four injections into the eye at monthly intervals. The patients will already have tried the standard of care without complete success. The patients will be randomized to receive either a high dose, a low dose or a sham control treatment. The study will evaluate whether the new treatment improves vision and whether it changes the underlying course of the disease in the eye.
Interventions
DRUGKVD001 Injection
Intravitreal KVD001 Injection
OTHERSham Procedure
Sham Procedure
Sponsors
KalVista Pharmaceuticals, Ltd.
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
* Confirmed diagnosis of Type I or Type II diabetes mellitus (DM). * BCVA of ≥19 letters (\ 20/400) and ≤73 letters (\ 20/40) in the study eye and ≥34 letters(\ 20/200 or better) in the fellow eye. * Presence of ciDME in the study eye defined as CST ≥305 μm in women and ≥320 μm in men * Subjects first anti-VEGF injection in the study eye occurred ≤36 months. * Subjects have received at least 3 anti-vascular endothelial growth factor (VEGF) injections in the study eye within a 6-month period. * The last anti-VEGF injection in the study eye is ≥ 8 weeks.
Exclusion criteria
* Evidence of ocular pathology (e.g. visually significant cataract) that impacts subject's vision in the study eye from any cause other than DME. * Evidence/presence of amblyopia, vitreomacular traction, epiretinal membrane, foveal atrophy, or foveal ischemia, or any other condition in the macula that is thought to impair the subject's vision (other than DME). * Prior treatment with panretinal photocoagulation or focal grid macular photocoagulation in the study eye within the previous 3 months. * Prior treatment with intravitreal (IVT) steroid in the study eye (in the previous 3 months for triamcinolone, previous 6 months for Ozurdex and at any time for Iluvien). * Prior treatment with topical NSAIDs or topical steroids in the study eye within 1 month. * Prior treatment with systemic corticosteroids or systemic anti-VEGF therapy within 3 months. * Prior vitrectomy in the study eye. * Prior intraocular surgery in the study eye except for cataract surgery. Cataract surgery within the previous 6 months in the study eye is excluded. * Intraocular pressure (IOP) of \>22 mmHg in the study eye or use of \>2 antiglaucoma agents (combination agents count as 2 agents) in the study eye. * Evidence of infectious dacrocystitis, significant blepharitis, active conjunctivitis, infectious keratitis, or scleritis in either eye, or any other condition that might affect the safety of the IVT injection. * Current active proliferative diabetic retinopathy (PDR), active anterior segment neovascularization (ASNV), active retinal neovascularization, or the presence of vitreous hemorrhage in the study eye. * Poorly controlled DM. * Uncontrolled hypertension * Prior treatment with ocriplasminin the study eye within 3 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| BCVA | 16 weeks | Change from Baseline in Best Corrected Visual Acuity (BCVA) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| DRSS | 16 weeks | Assessments of Diabetic Retinopathy Severity Score (DRSS, scale 10-85) to evaluate the percentage of eyes with a ≥2 step reduction in score from the baseline retinopathy severity as graded from fundus photography. Minimum and maximum values of the DRSS are 10 and 85, with the low end of the scale indicating absence of retinopathy which, as the score increases, so does the severity of the retinopathy such that a score of 85 is indicative of advanced proliferative diabetic retinopathy |
| CST | 16 weeks | Assessments of Central Subfold Thickness (CST) - analysis of covariance of change from baseline in the study eye at week 16 |
Countries
United States
Participant flow
Pre-assignment details
130 Patients were randomized but one patient withdrew prior to receiving any study treatments
Participants by arm
| Arm | Count |
|---|---|
| KVD001 Injection (High Dose) KVD001 Injection: Intravitreal KVD001 Injection 6ug | 41 |
| KVD001 Injection (Low Dose) KVD001 Injection: Intravitreal KVD001 Injection 3ug | 44 |
| Sham Procedure Sham Procedure: Sham Procedure | 44 |
| Total | 129 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 | 1 |
| Overall Study | Rescued without meeting criteria | 4 | 1 | 1 |
| Overall Study | Subject compliance | 2 | 0 | 0 |
| Overall Study | Use of rescue medication | 8 | 9 | 13 |
| Overall Study | Withdrawal by Subject | 2 | 3 | 1 |
| Overall Study | Worsening disease | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Total | Sham Procedure | KVD001 Injection (High Dose) | KVD001 Injection (Low Dose) |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 58 Participants | 21 Participants | 20 Participants | 17 Participants |
| Age, Categorical Between 18 and 65 years | 71 Participants | 23 Participants | 21 Participants | 27 Participants |
| Age, Continuous | 63.0 years STANDARD_DEVIATION 9.7 | 64.6 years STANDARD_DEVIATION 8.62 | 63.2 years STANDARD_DEVIATION 9.58 | 61.1 years STANDARD_DEVIATION 10.67 |
| Baseline BMI | 32.11 kg/(m*m) STANDARD_DEVIATION 6.778 | 31.58 kg/(m*m) STANDARD_DEVIATION 6.999 | 31.71 kg/(m*m) STANDARD_DEVIATION 5.367 | 33.00 kg/(m*m) STANDARD_DEVIATION 7.728 |
| Baseline Height (cm) | 167.31 cm STANDARD_DEVIATION 11.788 | 164.78 cm STANDARD_DEVIATION 12.638 | 167.98 cm STANDARD_DEVIATION 10.833 | 169.21 cm STANDARD_DEVIATION 11.579 |
| Baseline Weight (kg) | 89.74 kg STANDARD_DEVIATION 21.083 | 85.34 kg STANDARD_DEVIATION 20.139 | 88.88 kg STANDARD_DEVIATION 13.605 | 94.94 kg STANDARD_DEVIATION 26.404 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 41 Participants | 15 Participants | 19 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 88 Participants | 29 Participants | 22 Participants | 37 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Iris color Black | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Iris color Blue | 24 Participants | 6 Participants | 9 Participants | 9 Participants |
| Iris color Brown | 71 Participants | 24 Participants | 23 Participants | 24 Participants |
| Iris color Gray | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Iris color Green | 7 Participants | 3 Participants | 2 Participants | 2 Participants |
| Iris color Hazel | 25 Participants | 11 Participants | 7 Participants | 7 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 4 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 12 Participants | 3 Participants | 4 Participants | 5 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 | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 111 Participants | 37 Participants | 37 Participants | 37 Participants |
| Sex: Female, Male Female | 58 Participants | 23 Participants | 15 Participants | 20 Participants |
| Sex: Female, Male Male | 71 Participants | 21 Participants | 26 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 41 | 0 / 44 | 0 / 44 |
| other Total, other adverse events | 22 / 41 | 26 / 44 | 23 / 44 |
| serious Total, serious adverse events | 3 / 41 | 3 / 44 | 2 / 44 |
Outcome results
Primary
BCVA
Change from Baseline in Best Corrected Visual Acuity (BCVA)
Time frame: 16 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| KVD001 Injection (High Dose) | BCVA | 0.8 Letters | Standard Deviation 6.65 |
| KVD001 Injection (Low Dose) | BCVA | -0.3 Letters | Standard Deviation 8.36 |
| Sham Procedure | BCVA | -1.8 Letters | Standard Deviation 12.27 |
Secondary
CST
Assessments of Central Subfold Thickness (CST) - analysis of covariance of change from baseline in the study eye at week 16
Time frame: 16 weeks
Population: FAS Population with LOCF
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| KVD001 Injection (High Dose) | CST | 10.9 μm | Standard Deviation 104.67 |
| KVD001 Injection (Low Dose) | CST | 2.3 μm | Standard Deviation 108.83 |
| Sham Procedure | CST | 8.2 μm | Standard Deviation 123.9 |
Secondary
DRSS
Assessments of Diabetic Retinopathy Severity Score (DRSS, scale 10-85) to evaluate the percentage of eyes with a ≥2 step reduction in score from the baseline retinopathy severity as graded from fundus photography. Minimum and maximum values of the DRSS are 10 and 85, with the low end of the scale indicating absence of retinopathy which, as the score increases, so does the severity of the retinopathy such that a score of 85 is indicative of advanced proliferative diabetic retinopathy
Time frame: 16 weeks
Population: FAS Population with observed data
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| KVD001 Injection (High Dose) | DRSS | 0 percentage of participants |
| KVD001 Injection (Low Dose) | DRSS | 3.2 percentage of participants |
| Sham Procedure | DRSS | 0 percentage of participants |