Study to Identify and Determine Best Implementation Practices for Injectable Cabotegravir+Rilpivirine in the United States (US)

• Status: Active, not recruiting
• Trial end date: 2021-10-20
• Target enrollment: 0
• Participant gender: All

Summary

Chronic human immunodeficiency virus (HIV) infection in adults continues to be characterized by increased development of resistant virus, increased transmission of resistant virus and issues associated with the long-term toxicity of anti-retroviral therapy (ART), despite advances in development of new ART, which provides extensive insight in management of HIV-infected individuals. Cabotegravir (CAB) is a potent integrase inhibitor (INI) and rilpivirine (RPV) is a potent non-nucleoside reverse transcriptase inhibitor (NNRTI). A two-drug regimen (DR)with CAB plus RPV long acting (LA) product offers many potential advantages over daily oral regimens including better tolerability, improved compliance, adherence, less likely to develop resistance, and overall treatment satisfaction in virologically suppressed subjects. This is a single-arm, open-label, multicenter, short term facilitation study to evaluate the effect of an implementation strategy on the degree of acceptability, appropriateness, feasibility, fidelity and sustainability of clinical practices to deliver the CAB+RPV LA regimen to HIV infected subjects and to also measure subject satisfaction by recording timeliness of visits, length of visit and their education. Approximately 135 subjects will be enrolled in the study and the total duration of the study will be approximately 52-weeks.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: ViiV Healthcare
• Treatments: Rilpivirine

Criteria

Inclusion Criteria:

• Be able to understand and comply with protocol requirements, instructions, and restrictions;

• Understand the long-term commitment to the study and be likely to complete the study as planned;

• Be considered appropriate candidates for participation in an investigative clinical trial with oral and intramuscularly injectable medications (e.g., no active substance use disorder, acute major organ disease, or planned long-term work assignments out of the country, etc.).

All Participants eligible for enrolment in the study must meet all of the following criteria:

• Aged 18 years or older at the time of signing the informed consent.

• HIV-1 infected and must be on an active highly active antiretroviral therapy (HAART) (2 or 3 drug) regimen for at least 6 months prior to Screening. Any prior switch, defined as a change of a single drug or multiple drugs simultaneously, must have occurred due to tolerability/safety, access to medications, or convenience/simplification, and must NOT have been done for treatment failure (HIV-1 RNA >=200 c/mL).

Acceptable stable ARV regimens prior to Screening include 2 NRTIs plus:

• INI (either the initial or second Combination antiretroviral therapy (cART) regimen)

• NNRTI (either the initial or second cART regimen)

• Boosted prediction interval (PI) (or atazanavir [ATV] unboosted) (must be either the initial cART regimen or one historical within class switch is permitted due to safety/tolerability)

• Any suppressed participants on a triple ART regimen for at least 6 months who had their regimen switched to a 2DR of dolutegravir (DTG)/RPV

• Documented evidence of at least two plasma HIV-1 RNA measurements <50 c/mL in the 12 months prior to Screening: at least one within 6 months prior to Screening;

• Plasma HIV-1 RNA <50 c/mL at Screening;

• A female participant is eligible to participate if she is not pregnant (as confirmed by a negative urine human chorionic gonadotrophin (hCG) test at screen and at Day 1), 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:

• Documented tubal ligation

• Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion

• Hysterectomy

• 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 (refer to laboratory reference ranges for confirmatory levels)]. 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 enrolment.

b. 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, and 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.

• Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the consent form and in this protocol. Eligible participants or their legal guardians (and next of kin when locally required), must sign a written Informed Consent Form before any protocol-specified assessments are conducted. Enrolment of participants who are unable to provide direct informed consent is optional and will be based on local legal/regulatory requirements and site feasibility to conduct protocol procedures.

Exclusion Criteria:

• Within 6 months prior to Screening, plasma HIV-1 RNA measurement >=50 c/mL;

• During the previous 12 months, any confirmed HIV-1 RNA measurement >=200 c/mL Exclusionary medical conditions

• 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 (CD4+) counts <200 cells/microliter are not exclusionary

• 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 enrolment if the Investigator believes the risk of seizure recurrence is low.

• 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.

• The participant has a tattoo or other dermatological condition overlying the gluteus region which may interfere with interpretation of injection site reactions.

• Evidence of Hepatitis B virus (HBV) infection based on the results of testing for Hepatitis B surface antigen (HBsAg), Hepatitis B core antibody (anti-HBc), Hepatitis B surface antibody (anti-HBs) and HBV Deoxyribonucleic acid (DNA) as follows:

• Participants positive for HBsAg are excluded;

• Participants negative for anti-HBs but positive for anti-HBc (negative HBsAg status) and positive for HBV DNA are excluded Note: Participants positive for anti-HBc (negative HBsAg status) and positive for anti-HBs (past and/or current evidence) are immune to HBV and are not excluded.

• Participants who are anticipated to require HCV treatment within 12 months must be excluded. Asymptomatic individuals with chronic hepatitis C virus (HCV) infection will not be excluded; investigators must carefully assess if therapy specific for HCV infection is required. (HCV treatment on study may be permitted, following consultation and approval of the direct acting antiviral (DAA) drug based therapy being considered with the medical monitor).

• Participants with HCV co-infection will be allowed entry into this study if:

• Liver enzymes meet entry criteria

• HCV Disease has undergone appropriate work-up, and is not advanced. Additional information (where available) on participants with HCV coinfection at screening should include results from any liver biopsy, Fibroscan, ultrasound, or other fibrosis evaluation, history of cirrhosis or other decompensated liver disease, prior treatment, and timing/plan for HCV treatment.

• In the event that recent biopsy or imaging data is not available or inconclusive, the Fib-4 score will be used to verify eligibility

• Fib-4 score >3.25 is exclusionary

• Fib-4 scores 1.45 - 3.25 requires Medical Monitor consultation Fibrosis 4 Score Formula: (Age x AST) / (Platelets x ( sqr [ ALT ])

• 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 inclusion.

• 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.

• Current or anticipated need for chronic anti-coagulation with the exception of the use of low dose acetylsalicylic acid (<=325 milligram (mg) per day) or hereditary coagulation and platelet disorders such as haemophilia or Von Willebrand Disease.

• Corrected QT interval (QTc [Bazett]) >450 milli second (msec) or QTc (Bazett) >480 msec for subjects with bundle branch block). Exclusionary Laboratory Values or Clinical Assessments (a single repeat to determine eligibility is allowed).

• Any evidence of primary resistance based on the presence of any major known INI or NNRTI resistance-associated mutation, except for K103N, (International acquired immune deficiency syndrome [AIDS] Society [IAS]-USA) by any historical resistance test result.

• ALT >=5 × Upper Limit Normal (ULN) or ALT >=3xULN and bilirubin >=1.5xULN (with >35% direct bilirubin) over the last 6 months.

• Any verified Grade 4 laboratory abnormality. A single repeat test is allowed during the Screening phase to verify a result.

• Participant has estimated creatinine clearance <50 mL/min/1.73meter^2 via the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.

Concomitant Medications

• Exposure to an experimental drug or experimental vaccine within either 28 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 Day 1:

• radiation therapy;

• cytotoxic chemotherapeutic agents;

• tuberculosis therapy with the exception of isoniazid (isonicotinylhydrazid [INH]);

• anti-coagulation agents;

• Immunomodulators that alter immune responses such as chronic systemic corticosteroids, interleukins, or interferons. Note: Participants using short-term (e.g. <=21 days) systemic corticosteroid treatment; topical, inhaled and intranasal corticosteroids are eligible for enrolment.

• Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of Screening.

• Use of medications which are associated with Torsade de Pointes must be discussed with the Medical Monitor to determine eligibility.

• Subjects receiving any prohibited medication and who are unwilling or unable to switch to an alternate medication. Note: Any prohibited medications that decrease CAB or RPV concentrations should be discontinued for a minimum of four weeks or a minimum of three half-lives (whichever is longer) prior to the first dose and any other prohibited medications should be discontinued for a minimum of two weeks or a minimum of three half-lives (whichever is longer) prior to the first dose.