RILPIVIRINE for HIV-1 infection

Inclusion criteria

• {"criterion_text":"- Be able to understand and comply with protocol requirements, instructions, and restrictions."}
• {"criterion_text":"- Understand the long-term commitment to the study and be likely to complete the study as planned."}
• {"criterion_text":"- 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.)."}
• {"criterion_text":"- Must be on a stable antiretroviral regimen without present or past evidence of viral resistance, and no prior virological failure with agents of the NNRTI and INI class."}
• {"criterion_text":"- Plasma HIV-1 RNA <50 copies/mL at screening."}
• {"criterion_text":"- A female subject is eligible to participate if she is not pregnant (as confirmed by a negative serum hCG test at screening) and not lacting."}
• {"criterion_text":"- Adults ≥60 years, currently receiving an antiretroviral regimen for ≥6 months."}
• {"criterion_text":"- Patients who have given written informed consent."}

Exclusion criteria

• {"criterion_text":"- Plasma HIV-1 RNA measurement ≥50 copies/mL within 6 months prior to screening. Blips are allowed (increased viral load ≥50 copies/mL but <200 copies/mL preceded and followed by a viral load less than 50 copies/mL)"}
• {"criterion_text":"- Any acute laboratory abnormality at screening, which, in the opinion of the investigator, would preclude the subject’s participation in the study of an investigational compound."}
• {"criterion_text":"- Subject has estimated creatinine clearance <50mL/min per 1.73m2 via Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) method."}
• {"criterion_text":"- Subjects who are currently participating in or anticipate being selected for any other interventional and non-interventional study Observational studies and clinical trials that do not include treatments are allowed."}
• {"criterion_text":"- Alanine aminotransferase (ALT) ≥5 × upper limit of normal (ULN). Or ALT ≥3x ULN and bilirubin ≥1.5x ULN (with >35% direct bilirubin)."}
• {"criterion_text":"- Subjects who, in the investigator's judgment, posed a significant suicide risk. Subject’s recent history of suicidal behaviour and/or suicidal ideation should be considered when evaluating for suicide risk."}
• {"criterion_text":"- Any drug holiday during the window between initiating first HIV ART and 6 months prior to screening, except for brief periods (less than 1 month) where all ART was stopped due to tolerability and/or safety concerns."}
• {"criterion_text":"- Any switch to a second line regimen, defined as change of a single drug or multiple drugs simultaneously, due to virologic failure to NNRTI or INSTI (defined as a confirmed plasma HIV-1 RNA measurement ≥200 copies/mL after initial suppression to <50 copies/mL while on first line HIV therapy regimen)"}
• {"criterion_text":"- Subjects with HCV co-infection were allowed entry into this study if additional information (where available) on subjects with HCV co-infection at screening should include results from any liver biopsy, FibroScan-CAP, ultrasound, or other fibrosis evaluation, history of cirrhosis or other decompensated liver disease, prior treatment, and timing/plan for HCV treatment."}
• {"criterion_text":"- Subjects with HCV co-infection were allowed entry into this study if 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 Aspartate aminotransferase) / (Platelets x (sqr [alanine aminotransferase])."}
• {"criterion_text":"- Any pre-existing physical or mental condition (including substance use disorder) which, in the opinion of the investigator, may interfere with the subject’s ability to comply with the dosing schedule and/or protocol evaluations or which may compromise the safety of the subject."}
• {"criterion_text":"- Unstable liver disease (as defined by any of the following: presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, oesophageal 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)."}
• {"criterion_text":"- 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 subject unable to receive study medication."}
• {"criterion_text":"- 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 pharmacokinetic sampling, subjects with a history of sensitivity to heparin or heparin-induced thrombocytopenia must not be enrolled."}
• {"criterion_text":"- Current or anticipated need for chronic anti-coagulation with the exception of the use of low dose acetylsalicylic acid (≤325 mg) or hereditary coagulation and platelet disorders such as haemophilia or Von Willebrand Disease."}
• {"criterion_text":"- The subject has a tattoo or other dermatological condition overlying the gluteus region which may interfere with interpretation of injection site reactions."}
• {"criterion_text":"- Evidence of hepatitis B virus (HBV) infection based on the results of testing at screening for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), hepatitis B surface antibody (anti- HBs) and HBV DNA as follows: Subjects positive for HBsAg are excluded. Subjects negative for anti-HBs but positive for anti-HBc (negative HBsAg status) and positive for HBV DNA are excluded."}
• {"criterion_text":"- Asymptomatic individuals with chronic hepatitis C virus (HCV) infection were not excluded. Treatment for HCV is allowed if the patient requires it during the development of the study."}
• {"criterion_text":"- Subjects deemed at high risk of seizure (such as those with an existing poorly controlled seizure disorder, or considered at high risk of recurrence based on medical history)."}
• {"criterion_text":"- Participants receiving any prohibited medication and who are unwilling or unable to switch to an alternative medication (refer to section 11.1.4. for additional information)"}
• {"criterion_text":"- History of liver cirrhosis with or without hepatitis viral co-infection."}
• {"criterion_text":"- Participants with severe hepatic impairment (Class C) as determined by Child-Pugh classification."}
• {"criterion_text":"- No clinically important pharmacokinetic differences between subjects with severe renal impairment (CrCL <30 mL/min and not on dialysis) and matching healthy subjects were observed. No dosage adjustment is necessary for patients with mild to severe renal impairment (not on dialysis). Cabotegravir has not been studied in patients on dialysis."}
• {"criterion_text":"- Subjects with HCV co-infection were allowed entry into this study if liver enzymes meet entry criteria."}
• {"criterion_text":"- Subjects with HCV co-infection were allowed entry into this study if investigators should consult current treatment guidelines when considering choice of therapy for individuals with chronic hepatitis C virus infection. Participants with hepatitis C virus infection should have undergone appropriate work-up, the chronic hepatitis C infection should not be advanced, and not anticipated to require introduction of new HCV therapy (e.g. with oral direct acting antivirals) during the course of the study"}
• {"criterion_text":"- Any evidence of primary resistance based on the presence of any major known INSTI or NNRTI resistance-associated mutation."}

Primary endpoints

• {"endpoint_text":"- Proportion of PLHIV ≥ 60 years on stable ART that switch to CAB LA + RPV LA with plasma HIV-1 RNA ≥50 copies per mL at month 12 in the intention-to-treat exposed (ITT-E) population, per the US Food and Drug Administration’s Snapshot algorithm.","definition_or_measurement_approach":"Measured as the proportion of participants aged ≥60 years on stable ART who have plasma HIV-1 RNA ≥50 copies/mL at month 12 in the ITT-E population, assessed using the US FDA Snapshot algorithm."}

Spain

Earliest CTIS Part Ii Submission Date

10-12-2024

Latest Decision Or Authorization Date

05-05-2025

Processing Time Days

146

Number Of Sites

9

Number Of Participants

120

Primary sponsor

Full Name

Fundacion Para La Formacion E Investigacion Sanitaria De La Region De Murcia

Organisation Type

Educational Institution

Country Of Registered Address

Spain

Third parties

• {"country":"","full_name":"JANSSEN-CILAG INTERNATIONAL NV","duties_or_roles":"Listed as product organisation for REKAMBYS (product dictionary entry / marketing authorisation holder nameOrg)","organisation_type":"Commercial"}
• {"country":"","full_name":"VIIV HEALTHCARE B.V.","duties_or_roles":"Listed as product organisation for Vocabria (product dictionary entry / marketing authorisation holder nameOrg)","organisation_type":"Commercial"}