A Sub-study of Cabotegravir (CAB) and Rilpivirine (RPV) in Human Immunodeficiency Viruses (HIV)-Infected Participants
Condition: Human Immunodeficiency Virus Type 1 (HIV-1)
MeSH terms: Acquired Immunodeficiency Syndrome; HIV Infections; Immunologic Deficiency Syndromes
Intervention: Cabotegravir Injectable Suspension; Rilpivirine Injectable Suspension
Intervention description: CAB LA injectable suspension is a sterile white to slightly pink suspension containing 200 milligrams per milliliter (mg/mL) of GSK1265744 as free acid for administration by IM injection. CAB LA injectable suspension is to be stored at up to 30 degree Celsius and should not be frozen.; RPV LA injectable suspension is a sterile white suspension containing 300 mg/mL of RPV as the free base for administration by IM injection. RPV LA injectable suspension should be kept in the outer package and stored at 2-8 degree Celsius and should not be frozen. RPV LA should also be protected from light.
Intervention MeSH terms: Rilpivirine; Cabotegravir
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 118.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Cabotegravir; Efficacy; Human immunodeficiency virus; Pharmacokinetic; Rilpivirine; Safety; Tolerability

Summary:

      This sub-study will assess the pharmacokinetics (PK), safety, tolerability, virologic
      efficacy and health outcomes of CAB (GSK1265744) and RPV long acting (LA) in HIV-infected
      adult participants currently enrolled in the Antiretroviral Therapy as Long Acting
      Suppression every 2 Months (ATLAS2M [A2M]) study (NCT03299049).
    

Eligibility criteria:

        Inclusion Criteria:

        Sub-study specific Inclusion Criteria:

          -  Capable of giving sub-study specific informed consent.

          -  Eligible participants must have been on CAB LA + RPV LA regimen for a minimum of 152
             weeks while on the ATLAS2-M study. Any disruptions in dosing during ATLAS2-M must be
             discussed with the Medical Monitor for a final determination of eligibility into the
             sub-study.

          -  Plasma HIV-1 RNA <50 copies/mL at Sub-Study Screening.

        Inclusion criteria detailed for the ATLAS-2M main study apply to the sub-study:

          -  A female participant is eligible to participate if she is not pregnant (as confirmed
             by a negative serum human chorionic gonadotropin [hCG] test) not lactating, and at
             least one of the following conditions applies:

               1. Non-reproductive potential defined as:

                    -  Pre-menopausal females with one of the following:

                       i. Documented tubal ligation ii. Documented hysteroscopic tubal occlusion
                       procedure with follow-up confirmation of bilateral tubal occlusion iii.
                       Hysterectomy iv. Documented Bilateral Oophorectomy

                    -  Postmenopausal defined as 12 months of spontaneous amenorrhea [in
                       questionable cases a blood sample with simultaneous follicle stimulating
                       hormone (FSH) and estradiol levels consistent with menopause. Females on
                       hormone replacement therapy (HRT) and whose menopausal status is in doubt
                       will be required to use one of the highly effective contraception methods if
                       they wish to continue their HRT during the study. Otherwise, they must
                       discontinue HRT to allow confirmation of post-menopausal status prior to
                       study enrollment.

               2. Reproductive potential and agrees to follow one of the options listed in the
                  Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of
                  Reproductive Potential (FRP) from 30 days prior to the first dose of study
                  medication, throughout the study, for at least 30 days after discontinuation of
                  all oral study medications, and for at least 52 weeks after discontinuation of
                  CAB LA and RPV LA.

          -  The investigator is responsible for ensuring that participants understand how to
             properly use these methods of contraception.

        Exclusion Criteria:

        Sub-study specific Exclusion Criteria:

          -  Participants with more than 1 plasma HIV-1 RNA measurement >=50 copies/mL to <200
             copies/mL (virologic blip) within 24 weeks prior to sub-study Screening visit.

          -  Any Suspected Virologic Failure (HIV-RNA greater than [>]200 copies/mL as defined in
             during ATLAS-2M study.

          -  Participants planning to require oral bridging during participation in the ATLAS-2M
             sub-study.

          -  The participant has a tattoo or any dermatological condition overlying the thigh
             region which may interfere with interpretation of injection site reactions.

          -  Any condition which, in the opinion of the Investigator, may interfere with the
             absorption, distribution, metabolism or excretion of the study drugs or render the
             participant unable to receive study medication.

        Exclusion criteria detailed for the ATLAS-2M main study apply to the sub-study:

          -  Women who are pregnant, breastfeeding or plan to become pregnant or breastfeed during
             the study.

          -  Any evidence of a current Center for Disease Control and Prevention (CDC) Stage 3
             disease, except cutaneous Kaposi's sarcoma not requiring systemic therapy, and Cluster
             of Differentiation 4 positive (CD4+) counts <200 cells per microliter are not
             exclusionary.

          -  Participants with moderate to severe hepatic impairment.

          -  Any pre-existing physical or mental condition (including substance use disorder)
             which, in the opinion of the Investigator, may interfere with the participant's
             ability to comply with the dosing schedule and/or protocol evaluations or which may
             compromise the safety of the participant.

          -  Participants determined by the Investigator to have a high risk of seizures, including
             participants with an unstable or poorly controlled seizure disorder. A participant
             with a prior history of seizure may be considered for enrollment if the Investigator
             believes the risk of seizure recurrence is low. All cases of prior seizure history
             should be discussed with the Medical Monitor prior to enrollment.

          -  Participants who, in the investigator's judgment, pose a significant suicide risk.
             Participant's recent history of suicidal behavior and/or suicidal ideation should be
             considered when evaluating for suicide risk.

          -  Unstable liver disease (as defined by any of the following: presence of ascites,
             encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or
             persistent jaundice or cirrhosis), known biliary abnormalities (with the exception of
             Gilbert's syndrome or asymptomatic gallstones or otherwise stable chronic liver
             disease per investigator assessment).

          -  History of liver cirrhosis with or without hepatitis viral co-infection.

          -  Ongoing or clinically relevant pancreatitis.

          -  Clinically significant cardiovascular disease, as defined by history/evidence of
             congestive heart failure, symptomatic arrhythmia, angina/ischemia, coronary artery
             bypass grafting (CABG) surgery or percutaneous transluminal coronary angioplasty
             (PTCA) or any clinically significant cardiac disease.

          -  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 participant prior to randomization.

          -  Any condition which, in the opinion of the Investigator, may interfere with the
             absorption, distribution, metabolism or excretion of the study drugs or render the
             participant unable to receive study medication.

          -  History or presence of allergy or intolerance to the study drugs or their components
             or drugs of their class. In addition, if heparin is used during PK sampling,
             participants with a history of sensitivity to heparin or heparin-induced
             thrombocytopenia must not be enrolled.

          -  Current or anticipated need for chronic anti-coagulation with the exception of the use
             of low dose acetylsalicylic acid lesser than or equal to (<=)325 mg or hereditary
             coagulation and platelet disorders such as hemophilia or Von Willebrand Disease.

          -  Any verified Grade 4 laboratory abnormality. A single repeat test is allowed during
             the Screening phase to verify a result.

          -  Any acute laboratory abnormality at Screening, which, in the opinion of the
             investigator, would preclude the participant's participation in the study of an
             investigational compound.

          -  Participant has estimated creatine clearance <50mL per minute per 1.73 square meter
             via Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) Method.

          -  Alanine aminotransferase (ALT) >=3 × upper limit of normal (ULN) at Screening.

          -  Exposure to an experimental drug (with the exception of those in the ATLAS-2M study
             including CAB, CAB LA, and RPV, RPV LA) or experimental vaccine within either 30 days,
             5 half-lives of the test agent, or twice the duration of the biological effect of the
             test agent, whichever is longer, prior to Day 1 of this study.

          -  Treatment with any of the following agents within 28 days of Screening:

             i. radiation therapy; ii. cytotoxic chemotherapeutic agents; iii. tuberculosis therapy
             with the exception of isoniazid (isonicotinylhydrazid [INH]); iv. anti-coagulation
             agents; v. Immunomodulators that alter immune responses such as chronic systemic
             corticosteroids, interleukins, or interferons

          -  Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of Screening.

          -  Use of medications which are associated with Torsade de Pointes.

          -  Participants receiving any prohibited medication and who are unwilling or unable to
             switch to an alternate medication.