Resumen

Este estudio evaluará la eficacia, la seguridad y la durabilidad de una terapia antirretroviral (TAR) de acción prolongada con CAB LA + RPV LA en personas con VIH que presentan niveles detectables de virus a pesar de recibir TAR oral. El estudio también considerará los comentarios de los pacientes sobre su experiencia con este tratamiento.

Elegibilidad

Edad mínima: 12 YearsSexo: ALL

Criterios de inclusión

Age
\. Aged \>=12 years and \>=35 kg (at the time of obtaining informed consent).
Type of Participant and Disease Characteristics 2.HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, plasma HIV-1 RNA VL.
Plasma HIV-1 RNA \>1 000 c/mL and greater than (\<) 100 000 c/mL at Screening. 4.Evidence of insufficient virologic response to participant's current oral ART regimen within 18 months prior to study entry according to at least 1 of the following criteria: i.\<1 log10 decrease in HIV-1 RNA or HIV-1 RNA \>200 c/mL at 2 time points at least 4 weeks apart in individuals who have been prescribed oral ART for at least 3 consecutive months.
ii. Documented lapse in current oral ART regimen usage expected to result in HIV-1 viremia (defined as at least a 30-day consecutive period of non-use of oral ART) iii. Documented need for change from oral ART regimen that investigator attributes as primary reason for insufficient virologic response (e.g., safety findings and/or limited tolerability, clinically relevant DDIs).
Currently being treated with an oral ART regimen specific regimen to be recorded at Screening, and willing to continue taking that regimen until approximately 1 week after the Month 6 visit.
Pregnancy, Sex and Contraceptive/Barrier Requirements 5. Person of childbearing potential (POCBP) must have a negative serum or urine pregnancy test at screening and on Day 1.
Informed Consent/Assent 6.Informed consent/Assent must be provided as follows:
Adult participants (\>=18 years old) must be capable of giving signed informed consent as described in the full study protocol, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and stated in the full study protocol.
For adolescent participants (12 to \<18 years of age at screening), the parent(s) or legal guardian must be capable of giving signed informed consent.

Criterios de exclusión

• Medical Conditions
HIV-1 Subtype A6, if known from historical result.
Participants who are pregnant, breast/chest feeding or plan to become pregnant or breast/chest feed during the study.
Unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice), cirrhosis, known biliary abnormalities (with the exception of hyperbilirubinemia or jaundice due to Gilbert's syndrome or asymptomatic gallstones).
Individuals with both HIV and Hepatitis B virus (HBV) will be excluded from participating in studies where they would not be able to receive appropriate therapy for their HBV co-infection and therefore may be at risk of hepatitis B flare. Exclusion will be determined by evidence of HBV infection based on the results of testing at Screening for HBsAg, HBcAb, HBsAb and HBV.
History of liver cirrhosis with or without hepatitis viral co-infection.
Participants with severe hepatic impairment (Class C) as determined by Child-Pugh classification.
Participants with HCV co-infection will be excluded entry into this study if they are currently receiving anti-HCV therapy at baseline (Day 1).
Participants determined by the investigator to have a high risk of seizures, including participants with an unstable or poorly controlled seizure disorder.
History of sensitivity to any of the study medications or their components or drugs of their class, or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation.
Participants who in the investigator's judgment, pose a significant suicidality risk. Participant's history of suicidal behaviour and/or suicidal ideation should be considered when evaluating for suicide risk.
Any pre-existing physical or mental condition 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.
• Prior/Concomitant Therapy
Any previous use of CAB.
Current or anticipated need for chronic anti-coagulants.
Use of concomitant medications which are associated with Torsades de Pointes (TdP).
Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of Screening.
Treatment with any of the following agents within 28 days of Screening:
radiation therapy;
cytotoxic chemotherapeutic agents;
tuberculosis therapy with the exception of isoniazid;
anti-coagulation agents, with the exception of the use of low dose acetylsalicylic acid (\<=325mg);
immunomodulators that alter immune responses such as chronic systemic corticosteroids, interleukins, or interferons.
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 the first dose of investigational medicinal product (IP).
Participants receiving any protocol-prohibited medication and who are unwilling or unable to switch to an alternate medication.
• Prior/Concurrent Clinical Study Experience
Participant is currently participating in, or anticipates being selected for, any other interventional study.
• Diagnostic assessments
Any evidence of viral drug resistance based on the presence of any major RAM to INSTIs or NNRTIs in the Screening result; or, if known, in any historical resistance test 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.
Any verified Grade 4 laboratory abnormality, with the exception of Grade 4 lipid abnormalities. A single repeat test is allowed during the Screening period to verify a result.
ALT \>=5 times ULN or ALT \>=3×ULN and bilirubin \>=1.5×ULN (with \>35% direct bilirubin).
eGFR of \<30 mL/min/1.73 m2 via refitted, race-neutral CKD-EPIcr\_R method (adult participants) or \<50 mL/min/1.73 m2 using the Bedside Schwartz equation (adolescent participants).
Hemoglobin \<9.0 g/dL.
Corrected QT interval (QTc \>450 msec or QTc \>480 msec for participants with bundle branch block, calculated using ECGs performed in triplicate).
• Other exclusions
Unwilling to receive injections, or unable to receive gluteal injections.
The participant has gluteal implants or prosthesis; or a tattoo or other dermatological condition overlying the gluteus region which may interfere with interpretation of injection site reaction (ISRs).
Evidence of alcohol or substance use disorder within the previous 12 months, using standard methods for their site, that would interfere with the participant's safety.
Adolescents who are wards of the state or government. To assess any potential impact on participant eligibility with regard to safety, the investigator must refer to the Investigator's brochure (IB) and supplements, approved product labels, and/or local prescribing information for detailed information regarding warnings, precautions, contraindications, AEs, drug interactions, and other significant data pertaining to the study drugs.

Ubicaciones

GSK Investigational Site

Buenos Aires, Argentina

US GSK Clinical Trials Call Center · GSKClinicalSupportHD@gsk.com · 877-379-3718

RECRUITING

GSK Investigational Site

Buenos Aires, Argentina

US GSK Clinical Trials Call Center · GSKClinicalSupportHD@gsk.com · 877-379-3718

RECRUITING

GSK Investigational Site

Buenos Aires, Argentina

US GSK Clinical Trials Call Center · GSKClinicalSupportHD@gsk.com · 877-379-3718

RECRUITING

GSK Investigational Site

Capital Federal, Argentina

US GSK Clinical Trials Call Center · GSKClinicalSupportHD@gsk.com · 877-379-3718

RECRUITING

GSK Investigational Site

Ciudad Autonoma de Bueno, Argentina

US GSK Clinical Trials Call Center · GSKClinicalSupportHD@gsk.com · 877-379-3718

RECRUITING

GSK Investigational Site

Córdoba, Argentina

US GSK Clinical Trials Call Center · GSKClinicalSupportHD@gsk.com · 877-379-3718

RECRUITING

GSK Investigational Site

Rosario, Argentina

US GSK Clinical Trials Call Center · GSKClinicalSupportHD@gsk.com · 877-379-3718

RECRUITING

Estudio de fase 3b, abierto, aleatorizado, con brazo de control de atención estándar, multicéntrico y de superioridad, para evaluar la eficacia, seguridad y tolerabilidad de CAB LA + RPV LA inyectables en participantes virémicos que viven con VIH-1 (CROWN)

Resumen

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

CAB LA + RPV LA

Oral ART

Ubicaciones

GSK Investigational Site

GSK Investigational Site

GSK Investigational Site

GSK Investigational Site

GSK Investigational Site

GSK Investigational Site

GSK Investigational Site

Patrocinadores

Contactos

US GSK Clinical Trials Call Center

EU GSK Clinical Trials Call Center