Study of MP0112 Intravitreal Injection in Patients With Diabetic Macular Edema

Study Overview
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Brief Summary
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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.

Official Title
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A Phase I/II, Open-label, Single Ascending Dose Study Evaluating the Safety, Preliminary Efficacy, and Pharmacokinetics of Intravitreal MP0112 in Patients With Diabetic Macular Edema (DME)

Conditions
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Diabetic Macular Edema

Intervention / Treatment
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* Biological: MP0112


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MP0112 (0.04 mg)<br>Single 0.04 mg intravitreal injection of MP0112 in the study eye. | Biological: MP0112<br>* Single intravitreal injection of MP0112 in the study eye<br>|
| Experimental: MP0112 (0.15 mg)<br>Single 0.15 mg intravitreal injection of MP0112 in the study eye. | Biological: MP0112<br>* Single intravitreal injection of MP0112 in the study eye<br>|
| Experimental: MP0112 (0.4 mg)<br>Single 0.4 mg intravitreal injection of MP0112 in the study eye. | Biological: MP0112<br>* Single intravitreal injection of MP0112 in the study eye<br>|
| Experimental: MP0112 (1.0 mg)<br>Single 1.0 mg intravitreal injection of MP0112 in the study eye. | Biological: MP0112<br>* Single intravitreal injection of MP0112 in the study eye<br>|
| Experimental: MP0112 (2.0 mg)<br>Single 2.0 mg intravitreal injection of MP0112 in the study eye. | Biological: MP0112<br>* Single intravitreal injection of MP0112 in the study eye<br>|
| Experimental: MP0112 (3.6 mg)<br>Single 3.6 mg intravitreal injection of MP0112 in the study eye. | Biological: MP0112<br>* Single intravitreal injection of MP0112 in the study eye<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline, Week 16 | 
| 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). | Baseline, Week 16 | 
| 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. | 16 Weeks | 
| 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. | 1 Week | 
| 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. | 12 weeks |