Safety and Efficacy Study of Small Interfering RNA Molecule (Cand5) to Treat Diabetic Macular Edema

July 24, 2008 updated by: OPKO Health, Inc.

A Phase II, Pharmacokinetic, Randomized, Double-Masked, Controlled, Dose Comparison Study of Cand5 for Intravitreal Injection for the Treatment of Diabetic Macular Edema

The purpose of this study is to evaluate the pharmacokinetics, safety and preliminary efficacy of 3 doses of Cand5. Cand5 is a small interfering RNA molecule that selectively silences the mRNA encoding for VEGF. The target population are patients with diabetic macular edema.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Diabetic retinopathy is the leading cause of newly diagnosed blindness in the working age (20-74) population in the United States1 and diabetic macular edema (DME) is the leading cause of vision loss in diabetic retinopathy. DME is the result of the breakdown of the retinal capillary endothelium in patients with diabetes mellitus (Type I and II).

A key factor in the development of DME is the permeability of the blood-retinal barrier. The breakdown of the endothelial tight junctions of the capillary walls in the retinal vasculature leads to increased permeation of salts, proteins, and water from the capillary luminal side of the barrier and the accumulation of fluid in the extracellular space. Multiple agents appear to contribute to the disruption of the blood-retina barrier,including vasoactive agents, prostaglandin and vascular endothelial growth factor (VEGF). VEGF is a peptide that promotes neovascularization and increases vascular permeability. If the resulting fluid is more than the amount that can be removed through the active pump mechanism (retinal pigmented epithelium), fluids continue to accumulate and edema develops. When thickening evolves or threatens the center of the fovea there is a high risk of visual loss.

Cand5 is a synthetic double stranded RNA (dsRNA) oligonucleotide. The molecule is a duplex formed by the hybridization of two partially complementary single strand RNAs in which the 3' end are capped with 2 deoxyribose (dT) units. Hybridization occurs across 19 ribose base pairs to yield the Cand5 molecule. Cand5 has a molecular weight of 13,345 grams/mole. Cand5 selectively silences the mRNA encoding for VEGF.

A comparison will be made between the three (3) treatment arms with regard to safety, efficacy, and duration of effect to determine a safe and efficacious dose of Cand5 appropriate for evaluation in future pivotal trials.

Study Type

Interventional

Enrollment (Actual)

48

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Ohio
      • Beechwood, Ohio, United States, 44122
        • Retina Associates of Cleveland

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

21 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Patients must be male or female age 21 or older.
  2. Patient must sign (and be given) a copy of the written informed consent form.

  3. Patients must have the diagnosis of diabetes mellitus (type 1 or type 2). Patients with the following will be considered to be sufficient evidence that diabetes is present:

    • Current regular use of insulin for the treatment of diabetes mellitus OR
    • Current regular use of oral anti-hyperglycemia agents for the treatment of diabetes OR
    • Documented diabetes by WHO criteria
  4. Patients must have ETDRS best corrected visual acuity of 69 to 24 letters (20/40 to 20/320 Snellen Equivalent) in the study eye.
  5. Patients must have a mean retinal thickness on OCT ≥ 250 microns in the central subfield.

Exclusion Criteria:

  1. Patients with a history of chronic renal failure requiring dialysis or kidney transplant.

  2. A condition that, in the opinion of the investigator, would preclude participation in the study (e.g., unstable medical status including blood pressure and glycemic control), including:

    • Patients in poor glycemic control who, within the last 4 months, initiated intensive insulin treatment (a pump or multiple daily injections) or plan to do so in the next 4 months should not be enrolled.
    • Patients with HbA1C > 10%OR
    • Patients with systolic blood pressure greater than 170 mmHg and/or diastolic blood pressure greater than 100 mmHg (Note: If blood pressure is brought below 170/100 mmHg by anti-hypertensive treatment, patient can become eligible).
  3. Past panretinal photocoagulation (PRP) for diabetes within 12 weeks of screening or PRP expected to be needed in the next three months in the study eye.
  4. Focal laser therapy to the retina of the study eye within 12 weeks of screening.
  5. Any intraocular surgery or ocular laser procedures in the study eye within 12 weeks of screening.
  6. Participation in an investigational trial within 30 days of study entry that involved treatment with any drug that has not received regulatory approval at the time of study entry.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 1
3.0 mg/eye dose group
Drug: bevasiranib
Other Names:
  • Cand5
Experimental: 2
1.5 mg/eye dose group
Drug: bevasiranib
Other Names:
  • Cand5
Experimental: 3
0.2 mg/eye dose group
Drug: bevasiranib
Other Names:
  • Cand5

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Change from baseline at the 12-week evaluation in macular edema as measured by optical coherence tomography.

Secondary Outcome Measures

Outcome Measure
Mean BCVA line/letters change from baseline at the 12-week evaluation.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

OPKO Health, Inc.

Investigators

  • Study Director: Christine Du Castel, MD, Chiltern International

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2006

Primary Completion (Actual)

September 1, 2007

Study Completion (Actual)

December 1, 2007

Study Registration Dates

First Submitted

March 23, 2006

First Submitted That Met QC Criteria

March 23, 2006

First Posted (Estimate)

March 27, 2006

Study Record Updates

Last Update Posted (Estimate)

July 25, 2008

Last Update Submitted That Met QC Criteria

July 24, 2008

Last Verified

July 1, 2008

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ACU211

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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