Study 212669: A Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of GSK2798745 in Participants With Diabetic Macular Edema

• Status: Recruiting
• Trial end date: 2021-12-10
• Target enrollment: 0
• Participant gender: All

Summary

This is a multi-center, open-label, single arm, 28-day treatment in participants with DME. The study will be composed of 3 periods for all participants: Screening, 28-day Treatment period, and Follow-up visit (approximately 28 days after the final dose).

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: GlaxoSmithKline

Criteria

Inclusion Criteria:

• At least 18 to 75 years of age inclusive, at the time of signing the informed consent.

• Diagnosis of diabetes mellitus (type 1 or type 2).

• Confirmation of DME with center involvement in at least one eye, including those with focal or diffuse DME as determined by Investigator-determined fluorescein angiography.

• Retinal thickening (diabetic macular edema) involving the center of the fovea in the study eye as defined by Investigator-determined SD-OCT central subfield thickness greater than (>)340 microns for Heidelberg Spectralis or >320 for Zeiss Cirrus; if both eyes are eligible, the eye with the greater OCT center subfield score is selected as the study eye if all other criteria are met. SD-OCT assessments for individual patients must be taken with the same machine throughout the duration of the study.

• Early Treatment Diabetic Retinopathy Study (ETDRS)-Best Corrected Visual Acuity (BCVA) letter score of 80 letter or worse (Snellen equivalent: equivalent to 20/25) or worse in the study eye. The non-study fellow eye should equivalent or better at Baseline, pre-dose.

• Safe to withhold treatment of the study eye with laser photocoagulation, intravitreal steroid injection, or intravitreal vascular endothelial growth factor (VEGF) inhibitor for the duration of the study.

• Body weight greater than equal to (>=) 50 kilograms (kg) and Body mass index (BMI) within the range 18 to 40kg per square meter (inclusive) at screening.

• Male participants will be eligible to participate if they agree to the following first dose of study treatment until the follow-up visit: Refrain from donating sperm, plus either be abstinent from heterosexual or homosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent or Must agree to use contraception/barrier as detailed below: 1. Agree to use a male condom and female partner to use an additional highly effective contraceptive method with a failure rate of less than (<)1 percent (%) per year, 2. Should also be advised of the benefit for a female partner to use a highly effective method of contraception as a condom may break or leak when having sexual intercourse with a woman of childbearing potential who is not currently pregnant.

• A female participant is eligible to participate if she is not of childbearing potential.

• Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

• Participant is willing and able to return for all study visits and to comply with all protocol requirements and procedures.

• Participants capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the consent form.

Exclusion Criteria:

• Additional eye disease in the study eye that in the opinion of the Investigator could compromise assessment of SD-OCT, BCVA or imaging of the posterior pole by Fundus Photography (FP), fluorescein angiography, or is likely to require intervention during the study ( for example [e.g.], cataract, glaucoma with documented visual field loss, ischemic optic neuropathy, retinitis pigmentosa).

• History of choroidal neovascularization in the study eye, or current choroidal neovascularization in the fellow eye requiring treatment.

• Active Proliferative diabetic retinopathy (PDR) in the study eye or untreated active PDR in the fellow eye.

• Ischemic maculopathy on fluorescein angiography defined as a total area of capillary loss greater that 2-disc areas (>5millimeter square [mm^2]) within the ETDRA macular grid or a foveal avascular zone greatest linear diameter of >1000 microns.

• Intraocular surgery or laser photocoagulation in the study eye within 90 day of dosing which might compromise assessment of SD-OCT, BCVA or imaging of the posterior pole by FP, fluorescein angiography. Allowed in fellow eye.

• Use of intravitreal ranibizumab,or bevacizumab within 42 days (6 weeks), or aflibercept within 56 days (8 weeks) of dosing in the study eye. Allowed in fellow eye.

• Use of intraocular steroids in the study eye within 180 days of dosing. Allowed in fellow eye.

• Use of or expected need for intravitreal or intraocular treatment in the study eye during course of the study. Allowed in fellow eye.

• Use of any systemically administered anti-angiogenic agent (e.g., bevacizumab, sunitinib, cetuximab, sorafenib, pazopanib), approved or investigational, within 6 months of dosing.

• Evidence of vitreomacular traction as determined by the Investigator.

• Uncontrolled intraocular pressure >22 millimeters of mercury in the study eye despite treatment with glaucoma medication.

• Within 6 months prior to the Screening Visit, use of medications known to be toxic to the retina, lens or optic nerve (e.g., desferoximine, chloroquine/hydrochloroquine, chlorpromazine, phenothiazines, tamoxifen, interferons and ethambutol) or are implicated in the development of macular edema (e.g. thiazolidinesdiones, fingolimod).

• Uncontrolled diabetes as indicated by glycated hemoglobin (HbA1c) >10% at Screening.

• Active ulcer disease or gastrointestinal bleeding at the time of Screening (positive Fecal Occult Blood Test (FOBT) at screening).

• Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).

• History of stroke or seizure disorder within 1 year of Screening.

• Participant who, in the Investigator's opinion, poses a significant suicide risk. Evidence of serious suicide risk may include any history of suicidal behavior and/or any evidence of suicidal ideation on any questionnaires e.g., Type 4 or 5 on the Columbia Suicidality Severity Rating Scale (CSSRS) in the last 6 months (assessed at Screening).

• History or current evidence of any serious or clinically significant cardiac, gastrointestinal, renal, endocrine, neurologic, hematologic, infectious or other condition that is uncontrolled on permitted therapies or that would, in the opinion of the Investigator or the Medical Monitor, make the participant unsuitable for inclusion in this study.

• Alanine aminotransferase (ALT) >1.5 times upper limit of normal (ULN).

• Bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).

• Evidence of abnormal clinical laboratory finding prior to enrollment that, in the opinion of the Investigator, makes the participant unsuitable for the study.

• Corrected (QTc) interval >450 milliseconds (msec) or QTc >480 msec in participants with bundle branch block.

• Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study drug, unless in the opinion of the Investigator and GlaxoSmithKline (GSK) Medical Monitor the medication will not interfere with the study procedures or compromise participant safety.

• Use of a listed precluded medication, including strong inhibitors or inducers of cytochrome P450 (CYP) 3A or p-glycoprotein, within the restricted timeframe relative to the first dose of the study treatment.

• Participation in the study would result in loss of blood or blood products in excess of 500 milliliter within 3 months from screening.

• Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day.

• Current enrollment, or past participation within the last 60 days, of any clinical study involving an investigational study intervention, or any other type of medical research, before signing of consent for this study.

• Positive human immunodeficiency virus (HIV) antibody test.

• Presence of Hepatitis B surface antigen (HBsAg) at screening or within 3 months prior to first dose of study intervention.

• Positive Hepatitis C antibody test result at screening or within 3 months prior to starting study intervention.

• Positive Hepatitis C ribonucleic acid (RNA) test result at screening or within 3 months prior to first dose of study intervention.

• Cardiac troponin at screening > ULN for the assay.

• Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the Investigator or Medical Monitor, contraindicates participation in the study.

• Regular substance abuse including drug and/or alcohol consumption within 6 months prior to the study. Alcohol consumption is defined as: An average weekly intake of > 14 units. One unit is equivalent to 8 gram of alcohol: a half-pint (equivalent to 240 milliliters[mL]) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.