ING200336, Pharmacokinetic and Safety Study in Pregnant Women With Human Immuno Virus Infection
Condition: Infection, Human Immunodeficiency Virus; HIV Infections; Arthralgia
MeSH terms: Infections; Communicable Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; Arthralgia
Intervention: DTG 50 mg /ABC 600 mg /3TC 300 mg FDC tablets
Intervention description: The DTG 50 mg /ABC 600 mg /3TC 300 mg FDC tablet is a purple, oval, biconvex tablets. The tablet contains 52.6 mg DTG sodium which is equivalent to 50 mg DTG free acid, 702 mg ABC sulphate which is equivalent to 600 mg ABC and 300 mg 3TC.
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 4.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: dolutegravir/abacavir/lamivudine fixed dose combination; pregnant women; once daily; antiretroviral therapy-naive; HIV-1 Infection; integrase inhibitor

Summary:

      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.
    

Eligibility criteria:

        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