Study of MP0112 Intravitreal Injection in Patients With Diabetic Macular Edema

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)

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.

Study Overview

• Status: Terminated
• Conditions: Diabetic Macular Edema
• Intervention / Treatment: Biological: MP0112

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Wilmer Eye Institute
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Ophthalmic Consultants of Boston
  • Texas
    • Austin, Texas, United States, 78705
      • Retina Research Center
    • Houston, Texas, United States, 77030
      • Retina Consultants of Houston

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

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

What is the study measuring?

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
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
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

Collaborators and Investigators

• Sponsor: Allergan
• Collaborators: Molecular Partners AG

Study record dates

Study Major Dates

• Study Start: February 1, 2010
• Primary Completion (Actual): December 1, 2010
• Study Completion (Actual): December 1, 2010

Study Registration Dates

• First Submitted: January 1, 2010
• First Submitted That Met QC Criteria: January 4, 2010
• First Posted (Estimate): January 5, 2010

Study Record Updates

• Last Update Posted (Estimate): May 13, 2014
• Last Update Submitted That Met QC Criteria: April 14, 2014
• Last Verified: April 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Macular Edema; Edema
• Other Study ID Numbers: MP0112-CP02