Diabetic Macular Edema
Conditions
Brief summary
The purpose of this study is to assess the safety and tolerability of MP0112 (a novel, potentially long acting VEGF inhibitor) in patients with diabetic retinal edema.
Interventions
BIOLOGICALMP0112
Single intravitreal injection of MP0112 in the study eye
Sponsors
Molecular Partners AG
Allergan
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female age 18 years or older * Macular edema due to diabetic retinopathy * Best-corrected visual acuity in the study eye of 20/40 to 20/400 * Central subfield thickness ≥ 250 microns by OCT * Females of childbearing potential must have a negative serum pregnancy test at Screening * Male subjects must or be: 1) surgically sterilized for at least 6 months, or 2) use an appropriate method of barrier contraception (e.g., condoms with spermicide) and advise any sexual partner of child-bearing potential that she must also use a reliable method of contraception (e.g., hormonal contraceptive, intrauterine device, diaphragm with spermicide) during the study and for 30 days from study drug administration. * Ability to understand the nature of the study and give written informed consent * Willing, committed, and able to return for ALL clinic visits and complete all study-related procedures
Exclusion criteria
* Any indication of irreversible vision loss such as significant atrophy, scarring, fibrosis, or hyperpigmentation in the fovea * Presence of significant ocular abnormalities in the study eye that prevent retinal assessment, including media opacities, cataract, or inadequate papillary dilation * Presence of vision loss from another ocular disease other than DME * History of any intraocular surgery within 3 months of Baseline * History of intraocular injection of anti-VEGF agent or steroids within 3 months of Baseline * History of laser photocoagulation for macular edema within 4 months prior to Baseline * Uncontrolled hypertension \> 140 systolic or \> 95 diastolic * HbA1C ≥ 12% * Creatinine: \> 1.5 x upper limit of normal (ULN) * Alanine transaminase (ALT), aspartate transaminase (AST), and gamma-glutamyl transferase (GGT): \> ULN * White blood cells (WBC), hematocrit, and platelets: \< lower limit of normal (LLN) * Heart rate \< 60 beats per minute (bpm) or history of clinically significant bradycardia * History of human immunodeficiency virus (HIV), chronic hepatitis B, or chronic hepatitis C infections * Subjects with infections requiring hospitalization and/or antibiotic treatment 14 days prior to Baseline * Subjects with any medical condition that in the judgment of the investigator could poise unacceptable risk to the subject or compromise interpretation of the data to be collected
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events as a Measure of Safety and Tolerability | 16 weeks | Safety and tolerability was assessed by vital signs, clinical laboratory evaluations, ophthalmological examinations, intraocular pressure, the presence of anti-drug antibodies and the collection of adverse events. An adverse event was considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study were reported as adverse events. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Best-Corrected Visual Acuity (BCVA) | Baseline, Week 16 | BCVA was measured using an eye chart and was reported as the number of letters read correctly (ranging from 0 to 100 letters) in the study eye at Baseline and Week 16. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). The higher the letters read correctly on the eye chart the better the vision. |
| Change From Baseline in Foveal Thickness as Measured by Optical Coherence Tomography (OCT) | Baseline, Week 16 | Optical Coherence Tomography (OCT), a laser based non-invasive diagnostic system providing high-resolution imaging sections of the fovea (part of the retina), was performed in the study eye after pupil dilation at Baseline and Week 16. A negative change from Baseline indicated improvement (less foveal thickness). |
| Serum Levels of MP0112 | 16 Weeks | Blood samples were collected Pre-treatment (Baseline), Day 1 and 3, Weeks 1, 4, 12, 16. Serum samples (liquid portion of the blood after cells and clotting factors were removed) were sent to a laboratory for analysis. Levels of MP0112 were determined using an enzyme-linked immunosorbent assay. |
| Aqueous Humor Levels of MP0112 | 1 Week | Aqueous humor (the thin, watery fluid in the eye) samples were collected from anterior chamber taps and were sent to a laboratory for analysis. Levels of MP0112 were determined using an enzyme-linked immunosorbent assay. |
| Number of Participants With Positive Binding Anti-MP0112 Antibodies | 12 weeks | Blood samples were collected Pre-treatment (Baseline) and Weeks 4, 8 and 12. Samples were analyzed for Anti-MP0112 antibodies using an enzyme-linked immunosorbent assay. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| MP0112 (0.04 mg) Single 0.04 mg intravitreal injection of MP0112 in the study eye. | 6 |
| MP0112 (0.15 mg) Single 0.15 mg intravitreal injection of MP0112 in the study eye. | 6 |
| MP0112 (0.4 mg) Single 0.4 mg intravitreal injection of MP0112 in the study eye. | 6 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Physician Decision | 1 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | MP0112 (0.04 mg) | MP0112 (0.15 mg) | MP0112 (0.4 mg) | Total |
|---|---|---|---|---|
| Age, Continuous | 62.7 Years STANDARD_DEVIATION 8.4 | 67.5 Years STANDARD_DEVIATION 9.9 | 64.2 Years STANDARD_DEVIATION 10.3 | 64.8 Years STANDARD_DEVIATION 9.2 |
| Sex: Female, Male Female | 2 Participants | 3 Participants | 2 Participants | 7 Participants |
| Sex: Female, Male Male | 4 Participants | 3 Participants | 4 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 6 | 6 / 6 | 6 / 6 |
| serious Total, serious adverse events | 0 / 6 | 1 / 6 | 0 / 6 |
Outcome results
Primary
Number of Participants With Adverse Events as a Measure of Safety and Tolerability
Safety and tolerability was assessed by vital signs, clinical laboratory evaluations, ophthalmological examinations, intraocular pressure, the presence of anti-drug antibodies and the collection of adverse events. An adverse event was considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study were reported as adverse events.
Time frame: 16 weeks
Population: All treated participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MP0112 (0.04 mg) | Number of Participants With Adverse Events as a Measure of Safety and Tolerability | Adverse Events (AEs) | 3 Participants |
| MP0112 (0.04 mg) | Number of Participants With Adverse Events as a Measure of Safety and Tolerability | Serious Adverse Events | 0 Participants |
| MP0112 (0.04 mg) | Number of Participants With Adverse Events as a Measure of Safety and Tolerability | Ophthalmic AEs in the Study Eye | 3 Participants |
| MP0112 (0.04 mg) | Number of Participants With Adverse Events as a Measure of Safety and Tolerability | Ophthalmic AEs in the Fellow Eye | 1 Participants |
| MP0112 (0.15 mg) | Number of Participants With Adverse Events as a Measure of Safety and Tolerability | Ophthalmic AEs in the Fellow Eye | 3 Participants |
| MP0112 (0.15 mg) | Number of Participants With Adverse Events as a Measure of Safety and Tolerability | Adverse Events (AEs) | 6 Participants |
| MP0112 (0.15 mg) | Number of Participants With Adverse Events as a Measure of Safety and Tolerability | Ophthalmic AEs in the Study Eye | 5 Participants |
| MP0112 (0.15 mg) | Number of Participants With Adverse Events as a Measure of Safety and Tolerability | Serious Adverse Events | 1 Participants |
| MP0112 (0.4 mg) | Number of Participants With Adverse Events as a Measure of Safety and Tolerability | Ophthalmic AEs in the Fellow Eye | 5 Participants |
| MP0112 (0.4 mg) | Number of Participants With Adverse Events as a Measure of Safety and Tolerability | Serious Adverse Events | 0 Participants |
| MP0112 (0.4 mg) | Number of Participants With Adverse Events as a Measure of Safety and Tolerability | Ophthalmic AEs in the Study Eye | 5 Participants |
| MP0112 (0.4 mg) | Number of Participants With Adverse Events as a Measure of Safety and Tolerability | Adverse Events (AEs) | 6 Participants |
Secondary
Aqueous Humor Levels of MP0112
Aqueous humor (the thin, watery fluid in the eye) samples were collected from anterior chamber taps and were sent to a laboratory for analysis. Levels of MP0112 were determined using an enzyme-linked immunosorbent assay.
Time frame: 1 Week
Population: All treated participants who consented to participate.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MP0112 (0.04 mg) | Aqueous Humor Levels of MP0112 | 14 nM |
| MP0112 (0.15 mg) | Aqueous Humor Levels of MP0112 | 106 nM |
| MP0112 (0.4 mg) | Aqueous Humor Levels of MP0112 | 555 nM |
Secondary
Best-Corrected Visual Acuity (BCVA)
BCVA was measured using an eye chart and was reported as the number of letters read correctly (ranging from 0 to 100 letters) in the study eye at Baseline and Week 16. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). The higher the letters read correctly on the eye chart the better the vision.
Time frame: Baseline, Week 16
Population: All treated participants with data for a given time point were included for analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MP0112 (0.04 mg) | Best-Corrected Visual Acuity (BCVA) | Baseline (n=5,4,5) | 56.2 Letters | Standard Deviation 9.8 |
| MP0112 (0.04 mg) | Best-Corrected Visual Acuity (BCVA) | Week 16 (n=5,6,5) | 66.8 Letters | Standard Deviation 12.9 |
| MP0112 (0.15 mg) | Best-Corrected Visual Acuity (BCVA) | Baseline (n=5,4,5) | 59.0 Letters | Standard Deviation 4.8 |
| MP0112 (0.15 mg) | Best-Corrected Visual Acuity (BCVA) | Week 16 (n=5,6,5) | 55.5 Letters | Standard Deviation 10 |
| MP0112 (0.4 mg) | Best-Corrected Visual Acuity (BCVA) | Baseline (n=5,4,5) | 59.6 Letters | Standard Deviation 17.1 |
| MP0112 (0.4 mg) | Best-Corrected Visual Acuity (BCVA) | Week 16 (n=5,6,5) | 66.0 Letters | Standard Deviation 17.5 |
Secondary
Change From Baseline in Foveal Thickness as Measured by Optical Coherence Tomography (OCT)
Optical Coherence Tomography (OCT), a laser based non-invasive diagnostic system providing high-resolution imaging sections of the fovea (part of the retina), was performed in the study eye after pupil dilation at Baseline and Week 16. A negative change from Baseline indicated improvement (less foveal thickness).
Time frame: Baseline, Week 16
Population: All treated participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MP0112 (0.04 mg) | Change From Baseline in Foveal Thickness as Measured by Optical Coherence Tomography (OCT) | Baseline | 390.5 microns | Standard Deviation 104.3 |
| MP0112 (0.04 mg) | Change From Baseline in Foveal Thickness as Measured by Optical Coherence Tomography (OCT) | Change from Baseline at Week 16 (n=5,6,5) | -8.8 microns | Standard Deviation 78.4 |
| MP0112 (0.15 mg) | Change From Baseline in Foveal Thickness as Measured by Optical Coherence Tomography (OCT) | Baseline | 514.3 microns | Standard Deviation 146 |
| MP0112 (0.15 mg) | Change From Baseline in Foveal Thickness as Measured by Optical Coherence Tomography (OCT) | Change from Baseline at Week 16 (n=5,6,5) | -57.8 microns | Standard Deviation 170.3 |
| MP0112 (0.4 mg) | Change From Baseline in Foveal Thickness as Measured by Optical Coherence Tomography (OCT) | Baseline | 402.0 microns | Standard Deviation 98.8 |
| MP0112 (0.4 mg) | Change From Baseline in Foveal Thickness as Measured by Optical Coherence Tomography (OCT) | Change from Baseline at Week 16 (n=5,6,5) | -29.2 microns | Standard Deviation 96 |
Secondary
Number of Participants With Positive Binding Anti-MP0112 Antibodies
Blood samples were collected Pre-treatment (Baseline) and Weeks 4, 8 and 12. Samples were analyzed for Anti-MP0112 antibodies using an enzyme-linked immunosorbent assay.
Time frame: 12 weeks
Population: All treated participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MP0112 (0.04 mg) | Number of Participants With Positive Binding Anti-MP0112 Antibodies | 0 Participants |
| MP0112 (0.15 mg) | Number of Participants With Positive Binding Anti-MP0112 Antibodies | 0 Participants |
| MP0112 (0.4 mg) | Number of Participants With Positive Binding Anti-MP0112 Antibodies | 3 Participants |
Secondary
Serum Levels of MP0112
Blood samples were collected Pre-treatment (Baseline), Day 1 and 3, Weeks 1, 4, 12, 16. Serum samples (liquid portion of the blood after cells and clotting factors were removed) were sent to a laboratory for analysis. Levels of MP0112 were determined using an enzyme-linked immunosorbent assay.
Time frame: 16 Weeks
Population: All treated participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MP0112 (0.04 mg) | Serum Levels of MP0112 | NA Nanomolar (nM) |
| MP0112 (0.15 mg) | Serum Levels of MP0112 | NA Nanomolar (nM) |
| MP0112 (0.4 mg) | Serum Levels of MP0112 | NA Nanomolar (nM) |