Oral vs Injectable Therapy for HIV

(VOLITION Trial)

Recruiting at 60 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: ViiV Healthcare

Must not be taking: Anticoagulants, Immunomodulators, Torsade drugs

Disqualifiers: Pregnancy, Cardiovascular disease, Hepatitis B, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

171 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing two treatments for people with HIV-1 who haven't had previous treatments. Participants start with a pill to manage the virus and may later switch to an injection. The study aims to see how well these treatments work and how patients feel about them.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you are taking certain medications that are not allowed by the study protocol, and you must be willing to switch to an alternative if needed.

What data supports the effectiveness of the drug CAB + RPV LA for HIV treatment?

Research shows that the long-acting injectable drug CAB + RPV LA is effective in maintaining HIV suppression in patients whose viral load is already undetectable. It offers a convenient alternative to daily pills, with high rates of sustained viral suppression and positive patient feedback on convenience and tolerability. ^{1 2 3 4 5}

Is the long-acting injectable HIV treatment CAB + RPV LA safe for humans?

The long-acting injectable treatment CAB + RPV LA has been shown to have a favorable safety profile in clinical trials for people living with HIV, with patients reporting positive experiences regarding the convenience and tolerability of the injections. ^{1 2 5 6 7}

What makes the CAB + RPV LA drug unique for HIV treatment?

CAB + RPV LA is unique because it is the first long-acting injectable treatment for HIV, allowing patients to receive injections every 4 or 8 weeks instead of taking daily pills. This can help reduce the stigma, pill fatigue, and adherence challenges associated with daily oral medications. ^{1 5 8 9 10}

Eligibility Criteria

Adults with HIV-1 who haven't taken antiretroviral therapy before can join this trial. They must have a certain level of HIV in their blood and be able to consent to the study's requirements. People with severe liver issues, heart conditions, risk of suicide, untreated syphilis or hepatitis B infection, recent exposure to experimental drugs or vaccines, or those on certain medications are excluded.

Inclusion Criteria

Participants enrolled in France must be affiliated to, or a beneficiary of, a social security category

Participants having plasma HIV-1 RNA ≥1,000 c/mL at Screening

I have never taken antiretroviral drugs before.

Exclusion Criteria

Participants with treatment with any of the following agents within 28 days of Screening: radiation therapy, cytotoxic chemotherapeutic agents, tuberculosis therapy with the exception of isoniazid (isonicotinylhydrazid, INH), anti-coagulation agents, with the exception of the use of low dose acetylsalicylic acid (≤325 mg), 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, Treatment with any agent with documented activity against HIV-1 in vitro within 28 days of first dose of study treatment. Treatment with acyclovir/valacyclovir is permitted, Use of medications which are associated with Torsade de Pointes, Participants receiving any protocol-defined prohibited medication and who are unwilling or unable to switch to an alternate medication, Any verified Grade 4 laboratory abnormality, with the exception of Grade 4 lipid abnormalities, Any acute laboratory abnormality at Screening, which, in the opinion of the Investigator, would preclude the participant's participation in an interventional clinical trial, Participant has estimated creatine clearance <30 milliliter per minute (mL/min) per 1.73 square meter (m^2) using the refitted, race-neutral Chronic Kidney Disease Epidemiology Collaboration (CKDEPIcr_R) method, Alanine aminotransferase (ALT) ≥5 times the upper limit of normal (ULN); or ALT ≥3xULN and bilirubin ≥1.5xULN (with >35 percentage (%) direct bilirubin), Participants known or suspected to have acquired HIV-1 concurrent with use of protease-exposure prophylaxis (PrEP) or post-exposure prophylaxis (PEP) must be discussed with the Medical Monitor prior to enrolment, Participant has a gluteal implant/enhancements (including fillers); or tattoo or other dermatological condition overlying the gluteus region which may interfere with interpretation of injection site reactions, 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 drugs, 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, Participant is currently participating in, or anticipates being selected for, any other interventional study

My liver disease is stable and does not include severe symptoms or conditions.

I do not have untreated syphilis or have completed treatment for it at least 7 days ago.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Initial Treatment

Participants receive oral DTG/3TC once daily until virologic suppression is attained

Approximately 20 weeks

Maintenance Treatment

Participants choose to either continue oral DTG/3TC or switch to CAB + RPV LA every two months

11 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• CAB + RPV LA
• DTG/3TC

Trial Overview The trial is testing two drug regimens for treating HIV-1: an oral tablet (DTG/3TC) taken daily and long-acting injectable drugs (CAB + RPV LA) given every two months. Participants start with the oral tablet and after viral suppression can choose to switch to injections or continue pills.

Participant Groups

Group I: Participants Receiving DTG/3TC Fixed Dose Combination (FDC) Experimental Treatment 1 Intervention

Group II: Participants Receiving CAB + RPV LA Experimental Treatment 2 Interventions

Who Is Running the Clinical Trial?

ViiV Healthcare

Lead Sponsor

Trials

379

Recruited

479,000+

Founded

2009

Headquarters

London, England, UK

Known For

HIV Research

Top Products

- Tivicay (dolutegravir), - Triumeq (abacavir/dolutegravir/lamivudine), - Juluca (dolutegravir/rilpivirine), - Apretude (cabotegravir)

Dr. Harmony Garges

ViiV Healthcare

Chief Medical Officer

MD

Deborah Waterhouse

ViiV Healthcare

Chief Executive Officer since 2017

Bachelor's degree in Business Administration

PPD DEVELOPMENT, LP

Industry Sponsor

Trials

167

Recruited

38,000+

David Simmons

PPD DEVELOPMENT, LP

Chief Executive Officer since 2012

BSc in Applied Science from Georgia Institute of Technology

Martina Flammer

PPD DEVELOPMENT, LP

Chief Medical Officer since 2024

MD

PPD Development, LP

Industry Sponsor

GlaxoSmithKline

Industry Sponsor

Trials

4,834

Recruited

8,389,000+

Headquarters

London, UK

Known For

Vaccines & Medicines

Top Products

**Advair (salmeterol, fluticasone propionate)**, **Shingrix (shingles vaccine)**, **Augmentin (amoxicillin/clavulanate potassium)**, **Ventolin (salbutamol sulfate)

Dame Emma Walmsley

GlaxoSmithKline

Chief Executive Officer since 2017

MA in Classics and Modern Languages from Oxford University

Dr. Hal Barron

GlaxoSmithKline

Chief Medical Officer since 2018

MD from Harvard Medical School

PPD

Industry Sponsor

Trials

162

Recruited

36,600+

Dr. Austin Smith

PPD

Chief Medical Officer since 2020

Doctor of Medicine from the Royal College of Surgeons in Ireland

David Simmons

PPD

Chief Executive Officer since 2012

Bachelor’s degree in Applied Mathematics and Industrial Management from Carnegie Mellon University

Findings from Research

Long-acting injectable antiretroviral (ARV) treatments, like cabotegravir/rilpivirine (LA-CAB/RPV), offer a simplified alternative to daily oral medications for HIV, potentially improving adherence and health outcomes for patients.

LA-CAB/RPV is currently the only approved long-acting injectable regimen for HIV treatment in adults and adolescents who are already virologically suppressed, with ongoing studies exploring its use in broader populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-acting injectable antiretroviral therapy: will it change the future of HIV treatment? Brizzi, M., Pérez, SE., Michienzi, SM., et al.[2023]

Cabotegravir/rilpivirine (CAB/RPV) is the first complete injectable antiretroviral therapy approved for HIV treatment, offering a monthly intramuscular injection option that improves adherence compared to daily oral medications.

Clinical trials have shown CAB/RPV to achieve high rates of sustained viral suppression with a favorable safety profile, while also enhancing patient satisfaction due to its convenience and confidentiality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic review of cabotegravir/rilpivirine long-acting antiretroviral injectable and implementation considerations at an HIV specialty clinic. Howe, ZW., Norman, S., Lueken, AF., et al.[2022]

Long-acting injectable cabotegravir (CAB) combined with rilpivirine (RPV) is an effective maintenance therapy for HIV suppression in patients who have maintained an undetectable viral load for 3 to 6 months, providing an alternative to daily oral medications.

There is a growing interest in developing new long-acting injectable antiretroviral agents with different mechanisms of action, which are currently being tested in phase 2 and 3 clinical trials to further improve treatment options for patients unable to adhere to daily oral therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Acting Injectable Antiretroviral Agents for HIV Treatment and Prevention. Kim, YS.[2022]

Cabotegravir (CAB) combined with rilpivirine (RPV) is the first long-acting dual therapy approved for HIV-1 treatment, showing comparable maintenance of viral suppression over 160 weeks with low rates of virological failure.

This regimen offers a convenient alternative to daily oral therapy, as it is administered via intramuscular injections every 4 weeks, with minimal adverse effects and no negative impact on renal or bone health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabotegravir-Rilpivirine: The First Complete Long-Acting Injectable Regimen for the Treatment of HIV-1 Infection. Durham, SH., Chahine, EB.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Long-acting injectable antiretroviral therapy: will it change the future of HIV treatment? [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Therapeutic review of cabotegravir/rilpivirine long-acting antiretroviral injectable and implementation considerations at an HIV specialty clinic. [2022]

3. Korea (South) pubmed.ncbi.nlm.nih.gov

Long-Acting Injectable Antiretroviral Agents for HIV Treatment and Prevention. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Real-world implementation of dolutegravir plus lamivudine in people living with HIV in Southwest China. [2022]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Patient-Reported Outcomes Through 1 Year of an HIV-1 Clinical Trial Evaluating Long-Acting Cabotegravir and Rilpivirine Administered Every 4 or 8 Weeks (ATLAS-2M). [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Cabotegravir-Rilpivirine: The First Complete Long-Acting Injectable Regimen for the Treatment of HIV-1 Infection. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Clinical implementation of long-acting antiretroviral treatment in high-income countries: challenges and advantages. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Identifying appropriate candidates for long-acting antiretroviral therapy: findings from a survey of health care providers in the ATLAS-2M trial. [2021]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Frequency of genotypic factors possibly associated with cabotegravir/rilpivirine failure in antiretroviral treatment-naïve and -experienced HIV-1- infected population. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Demonstration Project of Long-Acting Antiretroviral Therapy in a Diverse Population of People With HIV. [2023]