Evaluation of Dolutegravir/Lamivudine and Cabotegravir/Rilpivirine for Virologic Suppression in Antiretroviral-Naive HIV-1 Infected Adults
- Trial ID
- 2023-503893-19-00
- Protocol
- 219700
- Sponsor
- Viiv Healthcare UK Limited
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the length of time required to achieve **virologic suppression** in antiretroviral-naive adult participants with **HIV-1 infection** using a regimen of dolutegravir/lamivudine (DTG/3TC). Additionally, the study aims to demonstrate the maintenance of virologic suppression over one year following a participant-determined switch to a long-acting regimen of cabotegravir plus rilpivirine (CAB + RPV LA) administered every two months. This is clinically relevant as it addresses the effectiveness of a simplified treatment regimen in maintaining viral suppression, which is crucial for long-term management of HIV-1.
Secondary objectives include:
- Evaluating the antiviral activity, immunologic effects, and incidence of disease progression with CAB + RPV LA and DTG/3TC over time.
- Assessing the development of viral resistance in participants experiencing confirmed virologic failure.
- Evaluating the safety and tolerability of CAB + RPV LA every two months and DTG/3TC administered once daily.
- Assessing patient-reported treatment satisfaction and bother from HIV-related symptoms.
- Evaluating health-related quality of life, anxiety, and depression.
- Assessing HIV-related stigma, feelings about diagnosis and treatment choice, and change in mood due to therapy.
- Exploring the association between treatment modality/frequency and fear of disclosure, daily reminder of HIV status, and adherence anxiety.
Participants
The clinical trial involves a total of **165 participants** diagnosed with **HIV-1 infection**. The study population includes both male and female adults aged **18 years and older**, who are antiretroviral-naïve, meaning they have not received any prior therapy with antiretroviral agents following their diagnosis. Participants are required to have a plasma HIV-1 RNA level of at least 1,000 copies/mL at screening. The trial includes individuals capable of providing written informed consent, with specific considerations for those enrolled in France, who must be affiliated with or beneficiaries of a social security category. The trial population was selected based on these criteria, ensuring a focus on adults who have not yet undergone antiretroviral treatment. The study does not specify any particular lifestyle considerations such as diet or physical activity. Both genders are represented, and the trial includes a vulnerable population, although specific details about this aspect are not provided.
Plans and Procedures
The clinical trial is a Phase IIIb, multi-center, non-randomized, parallel-group, open-label study designed to evaluate the efficacy, safety, and implementation effectiveness of **dolutegravir/lamivudine** as a first-line regimen, followed by an optional switch to long-acting intramuscular **cabotegravir** plus **rilpivirine** for the maintenance of virologic suppression in antiretroviral therapy-naive adults living with **HIV-1 infection**. The trial is expected to commence on December 26, 2023, and conclude by August 25, 2026. Participants will initially receive oral dolutegravir/lamivudine once daily, with the option to switch to a long-acting injectable regimen every two months after achieving virologic suppression.
The study involves several key visits, beginning with a screening visit to confirm eligibility based on criteria such as age, HIV-1 RNA levels, and antiretroviral-naive status. Following the screening, participants will undergo regular follow-up visits to monitor virologic suppression, safety, and patient-reported outcomes. The primary endpoint is the time to achieve virologic suppression, defined as an HIV viral load of less than 50 copies per milliliter. Secondary endpoints include maintaining virologic suppression over one year and assessing changes in CD4+ cell count and health-related quality of life.
Participants are expected to be involved in the study for a maximum of 28 days for the initial treatment period with dolutegravir/lamivudine, followed by up to 24 months for those who opt for the long-acting injectable regimen. Conditions that may lead to early termination from the study include confirmed virologic failure, occurrence of serious adverse events, or withdrawal of consent. The study aims to provide comprehensive data on the effectiveness and patient satisfaction of transitioning from an oral to a long-acting injectable regimen for the treatment of HIV-1.
Treatment
The clinical trial involves the administration of several experimental medications, each with specific pharmaceutical forms, dosages, and routes of administration. **Dovato** 50 mg/300 mg film-coated tablets, containing the active substances **lamivudine** and **dolutegravir sodium**, are administered orally. The dosage is set at one tablet per day, with a maximum treatment period of 28 days. The tablets are manufactured by VIIV Healthcare B.V. and are not formulated for pediatric use. The study-specific labeling is applied to the product, and participant compliance is monitored through regular assessments.
Another experimental medication used in the trial is **Vocabria** 400 mg prolonged-release suspension for injection, which contains the active substance **cabotegravir**. This medication is administered via intramuscular injection, with a maximum treatment period of 24 days. The suspension is also produced by VIIV Healthcare B.V. and is not intended for pediatric use. The study-specific labeling is applied, and compliance is ensured through scheduled injections and monitoring.
Additionally, **REKAMBYS** 900 mg prolonged-release suspension for injection, containing the active substance **rilpivirine**, is utilized in the trial. This medication is administered intramuscularly, with a maximum treatment period of 24 days. Manufactured by Janssen-Cilag International NV, the product is labeled specifically for the study and is not designed for pediatric use. Compliance is monitored through regular injection schedules and participant assessments.
Lastly, **Vocabria** 600 mg prolonged-release suspension for injection, also containing **cabotegravir**, is administered intramuscularly. The maximum treatment period is 24 days, and the product is manufactured by VIIV Healthcare B.V. The study-specific labeling is applied, and compliance is monitored through scheduled injections and participant evaluations. This formulation is not intended for pediatric use.
Efficacy
The efficacy of the clinical trial will be assessed through a series of primary and secondary endpoints focused on the suppression of the HIV virus in antiretroviral-naive adults living with HIV-1. The primary endpoints include the **time to virologic suppression**, defined as achieving an HIV viral load of less than 50 copies per milliliter (c/mL) from Day 1 with the use of dolutegravir/lamivudine (DTG/3TC), and maintaining this suppression after one year of treatment with cabotegravir plus rilpivirine long-acting (CAB + RPV LA) every two months.
Secondary endpoints will evaluate various parameters, including the proportion of participants with plasma HIV-1 RNA levels below 50 c/mL at Month 12, changes in plasma HIV-1 RNA and CD4+ cell counts over time, and the occurrence of virologic failure and disease progression. Additionally, the trial will assess the occurrence of viral resistance and adverse events, as well as changes in treatment satisfaction and health-related quality of life using validated tools such as the HIV Treatment Satisfaction Status Questionnaire (HIVTSQs), Symptom Distress Module (SDM), and WHOQoL-HIV-BREF. These assessments will be conducted at specified timepoints, including Day of Choice, Month 6, and Month 12 for participants on DTG/3TC, and Month 5 and Month 11 for those on CAB + RPV LA.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Age ≥18 years (or older, if required by local regulations) at the time of obtaining informed consent.
- Male or female. A female participant is eligible to participate if she is not pregnant (as confirmed by a negative serum human chorionic gonadotropin (hCG) test at Screening and a negative urine hCG test at Enrolment) and not lactating.
- Plasma HIV-1 RNA ≥1,000 c/mL at Screening.
- Antiretroviral-naïve (defined as no prior therapy with any antiretroviral agent following a diagnosis of HIV-1 infection) prior to enrolment.
- Participant is capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form and in this protocol. Eligible participants must sign a written ICF 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.
- Participants enrolled in France must be affiliated to, or a beneficiary of, a social security category.
Exclusion Criteria
- Women who are pregnant or breastfeeding or plan to become pregnant or breastfeed during the study.
- History or presence of allergy or intolerance to the study drugs 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 study participation.
- Ongoing or clinically relevant pancreatitis.
- Clinically significant cardiovascular disease, as defined by recent history (within the last 6 months) or current 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 Medical Monitor for inclusion of the participant prior to enrolment.
- Hereditary coagulation and platelet disorders (e.g. haemophilia or von Willebrand Disease); or current or anticipated need for chronic anti-coagulation, with the exception of the use of low-dose acetylsalicylic acid (≤325 mg).
- Participants with severe hepatic impairment (Class C) as determined by Child-Pugh classification.
- 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, or decompensated cirrhosis (e.g. ascites, encephalopathy, or variceal bleeding), 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.
- 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. All cases of prior seizure history should be discussed with the Medical Monitor prior to enrolment.
- 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.
- Signs and symptoms which, in the opinion of the Investigator, are suggestive of active SARS-CoV-2 infection within 14 days prior to enrolment.
- Untreated syphilis infection (positive rapid plasma reagin [RPR] at Screening without clear documentation of treatment) are excluded. Participants with a false positive RPR (with negative treponemal test) or serofast RPR result (persistence of a reactive nontreponemal syphilis test despite history of adequate therapy and no evidence of re-exposure) may enroll after consultation with the Medical Monitor. Participants who completed treatment at least 7 days prior to Screening are eligible.
- Exposure to an experimental drug 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 first dose of study treatment.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 France | Not Recruiting | 26 Dec 2023 | 15 |
 Germany | Not Recruiting | 26 Dec 2023 | 12 |
 Italy | Not Recruiting | 26 Dec 2023 | 16 |
 Spain | Not Recruiting | 26 Dec 2023 | 24 |
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 |
|---|---|---|---|---|---|---|
Dovato 50 mg/300 mg film-coated tablets | Test | FILM-COATED TABLETS | ORAL | 50999300 | 28 | PRD7413972 |
Dovato 50 mg/300 mg film-coated tablets | Test | FILM-COATED TABLETS | ORAL | 50999300 | 28 | PRD7413993 |
REKAMBYS 900 mg prolonged-release suspension for injection | Test | PROLONGED-RELEASE SUSPENSION FOR INJECTION | INTRAMUSCULAR INJECTION | 9009993 | 24 | PRD8603225 |
Vocabria 400 mg prolonged-release suspension for injection | Test | PROLONGED-RELEASE SUSPENSION FOR INJECTION | INTRAMUSCULAR INJECTION | 4009992 | 24 | PRD8594098 |
Vocabria 600 mg prolonged-release suspension for injection | Test | PROLONGED-RELEASE SUSPENSION FOR INJECTION | INTRAMUSCULAR INJECTION | 6009993 | 24 | PRD8594142 |