ING200336, Pharmacokinetic and Safety Study in Pregnant Women With Human Immuno Virus Infection

ING200336: A Prospective, Interventional Pharmacokinetic and Safety Study of DTG/ABC/3TC in Pregnant Women

In this study, the dolutegravir/abacavir/lamivudine (DTG/ABC/3TC) fixed dose combination (FDC) tablet is being made available to women who become pregnant while participating in study ING117172. Continuation of antiretroviral therapy (ART) is key to both mother and the unborn fetus in order to maintain virologic suppression in the mother (thereby decreasing the risk for maternal disease progression), but also to reduce the risk of maternal-fetal transmission of human immunodeficiency virus type 1 (HIV-1) to her unborn child. This study also offers the first opportunity to investigate the impact of pregnancy on DTG pharmacokinetics (PK). This is an open-label, single arm interventional study. The number of women that will be enrolled into this study cannot be established a priori, as unintended pregnancies cannot be determined in advance. The maximum number of women would include all of those women randomized to DTG/ABC/3TC FDC (approximately 237), though unintended pregnancies in all of these women would not be anticipated.

Inclusion Criteria:

• HIV infected females participating in ING117172 on the DTG/ABC/3TC treatment arm who became pregnant with a singleton and have not met any safety or confirmed virologic withdrawal criteria.
• Signed and dated written informed consent is obtained from the subject or the subject's legal representative prior to screening.
• Willingness and intent to continue pregnancy
• Willingness to continue to receive DTG/ABC/3TC FDC.
• Willingness to enter the Antiretroviral Pregnancy Registry.
• Willingness to share medical information about herself and her infant for collection of delivery and infant outcomes as it relates to this study.
• Subjects enrolled in France: a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.

Exclusion Criteria:

• History of allergy/sensitivity to DTG, ABC and/or 3TC.
• History of severe pre-clampsia, eclampsia, or hemolysis, elevated liver enzymes and low platelet count (HELLP)
• Any evidence of an active Center for Disease Control and Prevention (CDC) Category C disease, except cutaneous Kaposi's sarcoma not requiring systemic therapy or historic or current CD4+ cell levels <200 cells/millimeter^3.
• Subjects with any degree of hepatic impairment.
• Ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous cell carcinoma, or cervical intraepithelial neoplasia; other localized malignancies require agreement between the investigator and the Study medical monitor for inclusion of the subject.
• Subjects who in the investigator's judgment, poses a significant suicidality risk. Recent history of suicidal behavior and/or suicidal ideation may be considered as evidence of serious suicide risk.
• Subjects with evidence of ongoing hepatitis B infection at screening, or anticipated need for Hepatitis C Virus therapy during the study.
• Treatment with any of the following agents within 28 days of Baseline: radiation therapy; cytotoxic chemotherapeutic agents; any immunomodulators that alter immune responses.
• Subjects enrolled in France: the subject has participated in any study using an investigational drug during the previous 60 days or 5 half-lives, or twice the duration of the biological effect of the experimental drug or vaccine, whichever is longer, prior to screening for the study or the subject will participate simultaneously in another clinical study.
• Any verified Grade 4 laboratory abnormality with the exception of Grade 4 lipid abnormalities (total cholesterol, triglycerides, high density lipoprotein [HDL] cholesterol, low density lipoprotein [LDL] cholesterol). A single repeat test is allowed during the Screening period to verify a result.
• Any acute laboratory abnormality observed in ING117172 or in any Screening laboratory assessments for ING200336, which, in the opinion of the Investigator, would preclude the subject's participation in the study.
• Hyperbilirubinemia of unknown etiology.
• Confirmed (with no more than 1 repeat evaluation) Grade >= 2 urine protein (dipstick), serum creatinine, total bilirubin, alanine aminotransferase or aspartate aminotransferase at the time of the screening lab.
• Subject has Creatinine Clearance of <50 mL/minute via Cockroft-Gault method at the time of the screening visit