Long Acting Cabotegravir plus Rilpivirine in People Living with HIV-1 (PLHIV) Aged ≥ 60 Years for 96 weeks.
- Trial ID
- 2022-502882-53-00
- Protocol
- IMIB-LOVER60-2022-03
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the proportion of participants aged 60 years or older, who are on stable oral antiretroviral therapy (ART), that switch to **Cabotegravir** (CAB) LA plus **Rilpivirine** (RPV) LA with plasma HIV-1 RNA levels of less than 50 copies/mL at month 12. This is assessed in the intention-to-treat exposed (ITT-E) population using the US FDA's Snapshot algorithm. This objective is clinically relevant as it aims to determine the efficacy of a long-acting injectable regimen in maintaining virological suppression in older adults living with HIV-1, potentially offering a more convenient treatment option compared to daily oral ART.
Secondary objectives include: - Evaluating other estimations of virological control at months 6, 12, and 24. - Assessing factors associated with confirmed virological failure (CVF). - Assessing the incidence of treatment-emergent genotypic and phenotypic resistance in participants with CVF. - Evaluating the immune effects of switching to CAB LA + RPV LA at months 6, 12, and 24. - Evaluating the safety and tolerability of CAB LA + RPV LA. - Assessing changes in metabolic control parameters at months 6, 12, and 24. - Evaluating changes in liver steatosis by controlled attenuation parameter (CAP) at months 12 and 24. - Evaluating changes in cardiovascular risk by Framingham REGICOR risk chart at months 12 and 24. - Assessing adherence to study and intramuscular injection visits through month 24. - Assessing changes in patient-reported outcomes (PROs) for HIV treatment satisfaction, preference, and perception of injection at months 6, 12, and 24. - Assessing changes in PROs related to stigma, anxiety, depression, loneliness, cognitive impairment, sleep disturbance, frailty, and illness intrusiveness at months 12 and 24. - Evaluating the number of episodes of plasma HIV-1 RNA ≥50 copies/mL that do not meet the criteria for confirmed virological failure throughout the study. - Evaluating the number of participants experiencing confirmed virological failures (CVF: two consecutive plasma HIV-1 RNA ≥200 copies/mL) throughout the study. - Assessing changes in the CD4/CD8 ratio from baseline to months 12 and 24.
Participants
The clinical trial involves participants diagnosed with **HIV-1**, focusing on individuals aged 60 years and older. Both male and female subjects are included in the study, with no specific vulnerable populations being targeted. Participants are required to be on a stable antiretroviral regimen for at least six months, with plasma HIV-1 RNA levels below 50 copies/mL at screening. The trial population was selected based on their ability to understand and comply with protocol requirements, and their likelihood to complete the study as planned. Participants must not have any active substance use disorder, acute major organ disease, or planned long-term work assignments out of the country. The sponsor has not provided information regarding the total number of participants. Lifestyle considerations such as diet and physical activity are not specified in the available data.
Plans and Procedures
The clinical trial is designed to evaluate the efficacy of a combination therapy involving **cabotegravir** and **rilpivirine** in individuals aged 60 years and older living with **HIV-1**. This study is structured as a randomized, double-blind, controlled trial, with a total duration of 96 weeks. Participants will be randomly assigned to receive either the investigational treatment or a control, ensuring that neither the participants nor the investigators are aware of the group assignments, thus maintaining the integrity of the trial results.
The trial will commence with an inclusion (screening) visit, where potential participants will be assessed against the inclusion criteria, such as being on a stable antiretroviral regimen with plasma HIV-1 RNA levels below 50 copies/mL. Eligible participants will then proceed to the baseline visit, where they will receive their first dose of the investigational treatment via **intramuscular injection**. Follow-up visits will occur at regular intervals to monitor the participants' health, adherence to the treatment protocol, and any adverse events. These visits are crucial for collecting data on the primary endpoint, which is the proportion of participants with plasma HIV-1 RNA levels below 50 copies/mL at month 12, as per the US FDA's Snapshot algorithm.
The end-of-study visit will mark the conclusion of the participant's involvement in the trial, where final assessments will be conducted to evaluate the long-term effects of the treatment. The expected length of participant involvement is approximately 24 months, with conditions for early termination including non-compliance with the study protocol, withdrawal of consent, or the occurrence of significant adverse events. The trial aims to provide valuable insights into the effectiveness of long-acting antiretroviral therapy in an older population, potentially informing future treatment strategies for **HIV-1**.
Treatment
The clinical trial involves the administration of **REKAMBYS**, a **900 mg prolonged-release suspension for injection** containing the active substance **rilpivirine**. This pharmaceutical form is designed for **intramuscular injection** and is administered once every four weeks. The maximum treatment period for this medication is 24 months. Rilpivirine is a chemical substance, and its administration is intended to maintain therapeutic drug levels over an extended period, reducing the frequency of dosing compared to oral formulations. Participant compliance is monitored through scheduled visits and assessments to ensure adherence to the dosing schedule.
In addition to REKAMBYS, the trial also includes the administration of **Vocabria**, a **600 mg prolonged-release suspension for injection** containing the active substance **cabotegravir**. Similar to REKAMBYS, Vocabria is administered via **intramuscular injection** every four weeks, with a maximum treatment duration of 24 months. Cabotegravir is also a chemical substance, and its prolonged-release formulation is designed to provide consistent drug exposure, minimizing the need for daily oral intake. Compliance with the dosing regimen is monitored through regular clinical evaluations and participant feedback.
No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are utilized in this study. The trial focuses solely on the efficacy and safety of the combination of REKAMBYS and Vocabria in the specified patient population. The study protocol includes detailed instructions for drug administration, dosing schedules, and monitoring procedures to ensure the integrity and reliability of the trial outcomes.
Efficacy
Efficacy in this clinical trial will be assessed by evaluating the primary endpoint, which is the proportion of participants aged 60 years and older, living with HIV-1, who switch from a stable oral antiretroviral therapy (ART) to a combination of long-acting cabotegravir (CAB LA) and **rilpivirine** (RPV LA), and maintain plasma HIV-1 RNA levels below 50 copies per mL at month 12. This assessment will be conducted in the intention-to-treat exposed (ITT-E) population, following the US Food and Drug Administration's Snapshot algorithm. The trial aims to monitor the efficacy of the treatment regimen over a 96-week period, with the primary efficacy measurement scheduled at the 12-month mark. The trial will utilize validated laboratory tests to measure plasma HIV-1 RNA levels, ensuring accurate and reliable data collection for efficacy analysis.
Inclusion and Exclusion 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.).
- 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.
- Plasma HIV-1 RNA <50 copies/mL at screening.
- 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.
- Adults ≥60 years, currently receiving an antiretroviral regimen for ≥6 months.
- Patients who have given written informed consent.
Exclusion Criteria
- 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)
- 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).
- 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)
- History of liver cirrhosis with or without hepatitis viral co-infection.
- Participants with severe hepatic impairment (Class C) as determined by Child-Pugh classification.
- 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.
- Subjects with HCV co-infection were allowed entry into this study if liver enzymes meet entry criteria.
- 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
- Any evidence of primary resistance based on the presence of any major known INSTI or NNRTI resistance-associated mutation.
- 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.
- Subject has estimated creatinine clearance <50mL/min per 1.73m2 via Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) method.
- 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.
- Alanine aminotransferase (ALT) ≥5 × upper limit of normal (ULN). Or ALT ≥3x ULN and bilirubin ≥1.5x ULN (with >35% direct bilirubin).
- 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.
- 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.
- 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)
- 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.
- 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]).
- 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.
- 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.
- 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.
- 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.
- The subject 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 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.
- 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.
- 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).
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Spain | Not Recruiting | 01 Jan 2025 | 120 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Vocabria 600 mg prolonged-release suspension for injection | Test | PROLONGED-RELEASE SUSPENSION FOR INJECTION | INTRAMUSCULAR INJECTION | 600 | 24 | PRD8594142 |
REKAMBYS 900 mg prolonged-release suspension for injection | Test | PROLONGED-RELEASE SUSPENSION FOR INJECTION | INTRAMUSCULAR INJECTION | 900 | 24 | PRD8603225 |