Dolutegravir + Rilpivirine for HIV

Recruiting at 5 trial locations

Overseen By EU GSK Clinical Trials Call Center

Age: < 18

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: ViiV Healthcare

Must be taking: Antiretroviral therapy

Must not be taking: Interferon, Torsades de Pointes

Disqualifiers: Cardiac disease, Liver disease, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

20 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to provide data on the pharmacokinetic (PK), safety, tolerability, efficacy and acceptability of this fixed dose combination (FDC) single tablet 2-drug regimen for virologically suppressed (HIV-1 RNA \[Ribonucleic Acid\] \< 50 \[cells per milliliter\] c/mL) children 6 to less than 12 years of age, weighing at least 25 kilogram (kg).

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop your current medications, but it requires that participants have been on the same antiretroviral therapy (ART) regimen for the 6 months before joining. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug Dolutegravir/Rilpivirine for HIV?

Research shows that switching to the drug Dolutegravir/Rilpivirine helps maintain control of the HIV virus in patients who are already successfully managing their condition with other treatments. It is generally well tolerated and may have benefits for kidney and bone health compared to other treatments. ^{1 2 3 4 5}

Is Dolutegravir + Rilpivirine safe for humans?

Dolutegravir + Rilpivirine is generally well tolerated in humans, with common side effects including headache and diarrhea. It has shown favorable effects on kidney and bone health compared to other treatments and is considered safe for people who are already stable on their current HIV treatment. ^{1 2 3 6 7}

What makes the drug Dolutegravir/Rilpivirine unique for treating HIV?

Dolutegravir/Rilpivirine is unique because it is the first two-drug single-tablet regimen approved for HIV-1 treatment, offering a simpler alternative to the standard triple-drug therapies. It is taken once daily and is effective for patients who are already virologically suppressed, with benefits like fewer drug interactions and positive effects on kidney and bone health. ^{1 2 3 5 7}

Research Team

GSK Clinical Trials

Principal Investigator

ViiV Healthcare

Eligibility Criteria

This trial is for HIV-1 infected children aged 6 to less than 12 years, weighing at least 25 kg. They must have been on the same antiretroviral therapy for the past six months and have a viral load of less than 50 copies/mL. Participants should not be pregnant or breastfeeding and if of reproductive potential, agree to use two contraception methods.

Inclusion Criteria

For participants of reproductive potential (defined as having reached menarche), not pregnant based on testing performed at Screening (i.e., from a specimen collected within 30 days prior to entry) and at Baseline/Day 1

For participants of reproductive potential who are engaging in sexual activity that could lead to pregnancy, willing to use two methods of contraception while receiving study drug and for approximately one month after permanently discontinuing study drug, based on participant/parent/guardian report at entry

I am a child aged 6-11 with HIV-1.

Exclusion Criteria

Documented HIV-1 RNA result greater than or equal to the lower limit of detection of the assay based on a specimen collected in the 12 months (365 days) prior to Screening

Any ≥ grade 3 result for the following based on grading per the Division of Acquired Immunodeficiency Syndrome (AIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events: Haemoglobin (<8.5 gram per deciliter [g/dL] or <5.25 millimoles per liter [mmol/L]); Absolute neutrophil count (<600 cells/mm^3 or <0.600 x 10^9 cells/L); Platelet count (<50,000 cells/mm^3 or <50.00 x 10^9 cells/L); Estimated glomerular filtration rate (eGFR: <60 ml/min/1.73m^2); ALT (≥5.0 x Upper limit of Normal [ULN]); Aspartate Aminotransferase (AST) (≥5.0 x ULN)

Has the following combination of laboratory test results at screening: Alanine transaminase [ALT] greater than or equal to 3 x ULN and total bilirubin greater than or equal to 1.5 x ULN and direct bilirubin greater than 35% of total bilirubin

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive the fixed dose combination of Dolutegravir/Rilpivirine

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Dolutegravir/Rilpivirine FDC

Trial Overview The study tests the pharmacokinetics (how the drug moves through a child's body), safety, tolerability, efficacy, and acceptability of Dolutegravir/Rilpivirine in tablet form for kids who are already responding well to HIV treatment.

Participant Groups

Group I: Dolutegravir(DTG)/Rilpivirine (RPV) Experimental Treatment 1 Intervention

Dolutegravir/Rilpivirine FDC is already approved in United States, European Union for the following indications:

Approved in United States as Juluca for:

• HIV-1 infection in adults who are virologically suppressed (HIV-1 RNA <50 copies/mL) on a stable antiretroviral regimen for at least 6 months with no history of treatment failure and no known mutations associated with resistance to the individual components of Juluca

Approved in European Union as Dolutegravir/Rilpivirine for:

• HIV-1 infection in adults who are virologically suppressed (HIV-1 RNA <50 copies/mL) on a stable antiretroviral regimen for at least 6 months with no history of treatment failure and no known mutations associated with resistance to the individual components of Dolutegravir/Rilpivirine

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

Janssen Research & Development, LLC

Industry Sponsor

Trials

1,022

Recruited

6,408,000+

Giacomo Salvadore

Janssen Research & Development, LLC

Chief Medical Officer since 2023

MD from the University of Rome, Tor Vergata

Ricardo Attar

Janssen Research & Development, LLC

Chief Executive Officer since 2008

PhD in Molecular Biology from the University of Buenos Aires

Findings from Research

Dolutegravir/rilpivirine (Juluca®) is the first two-drug single-tablet regimen approved for HIV-1 treatment, showing maintained virological suppression over 48 weeks in treatment-experienced patients who switched from their current antiretroviral regimen in two phase III trials (SWORD-1 and SWORD-2).

The regimen was well tolerated, with better renal and bone health outcomes compared to traditional ART, and demonstrated durable virological suppression for up to 100 weeks, making it a convenient option for adults with HIV-1 who are virologically suppressed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dolutegravir/Rilpivirine: A Review in HIV-1 Infection. Blair, HA.[2022]

In a study of 145 patients followed for a median of 101 weeks, switching to dolutegravir (DTG) plus rilpivirine (RPV) resulted in 95.2% of patients achieving viral suppression with less than 50 copies/mL of HIV-1 RNA, demonstrating the efficacy of this treatment strategy.

The treatment also led to significant improvements in metabolic health, including a notable decrease in the LDL-C/HDL-C cholesterol ratio and normalization of various laboratory parameters, indicating a positive safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dolutegravir Plus Rilpivirine as a Switch Option in cART-Experienced Patients: 96-Week Data. Capetti, AF., Cossu, MV., Sterrantino, G., et al.[2020]

In a real-world study of 348 patients with a long history of HIV infection, the DTG/RPV regimen demonstrated an efficacy rate of 89.7% in achieving viral suppression at 48 weeks, indicating its effectiveness as a treatment option.

The switch to DTG/RPV was well-tolerated with minimal adverse effects, showing favorable changes in lipid and liver profiles, while kidney function remained stable, suggesting a safe profile for patients with complex treatment histories.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of dolutegravir/rilpivirine in real-world clinical practice. GeSIDA study 1119. Palacios, R., Gómez-Ayerbe, C., Casado, JL., et al.[2023]

In a study of 209 people living with HIV/AIDS on dolutegravir (DTG) and rilpivirine (RPV) dual therapy, 92.9% maintained viral loads below 50 copies/mL, indicating the therapy's overall efficacy in maintaining virological suppression.

However, 40% of those with viral loads above 50 copies/mL had subtherapeutic drug concentrations, suggesting that low drug levels may contribute to virological failure in some patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic drug monitoring and virological response at week 48 in a cohort of HIV-1-infected patients switching to dolutegravir/rilpivirine dual maintenance therapy (ANRS-MIE-BIRIDER study). Lemaitre, F., Lagoutte-Renosi, J., Gagnieu, MC., et al.[2023]

In a study of 35 treatment-experienced patients switching to a dolutegravir (DTG) plus rilpivirine (RPV) regimen, 91.4% achieved virological suppression (viral load <50 copies/mL) at 48 weeks, indicating high effectiveness.

The switch to DTG plus RPV not only maintained virological suppression without significant adverse effects but also improved patient adherence to ART from 65.6% to 93.8%, while reducing annual treatment costs by €665.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness, Safety, and Costs of a Treatment Switch to Dolutegravir Plus Rilpivirine Dual Therapy in Treatment-Experienced HIV Patients. Revuelta-Herrero, JL., Chamorro-de-Vega, E., Rodríguez-González, CG., et al.[2020]

In a study of 104 HIV-infected patients who switched to dolutegravir/rilpivirine (DTG/RPV), the treatment showed an efficacy rate of 88.4% at 24 weeks, indicating it effectively maintains viral suppression.

The treatment was well-tolerated with no patients discontinuing due to adverse events, and it resulted in a significant reduction in triglyceride levels, suggesting an improvement in the lipid profile of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Dolutegravir Plus Rilpivirine in Treatment-Experienced HIV-Infected Patients: The DORIVIR Study. Palacios, R., Mayorga, M., González-Domenech, CM., et al.[2020]

The combination of dolutegravir (DTG) and rilpivirine (RPV) is an effective dual therapy for HIV-1, maintaining virological suppression for up to 100 weeks with low rates of failure, making it a viable option for patients who have been stable on triple therapy.

This single-tablet regimen is convenient, has a high barrier to resistance, and is associated with fewer drug interactions and positive effects on lipid, renal, and bone health, particularly beneficial for patients with complex health conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dolutegravir-Rilpivirine, Dual Antiretroviral Therapy for the Treatment of HIV-1 Infection. Hester, EK., Astle, K.[2020]

References

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

Dolutegravir/Rilpivirine: A Review in HIV-1 Infection. [2022]

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

Dolutegravir Plus Rilpivirine as a Switch Option in cART-Experienced Patients: 96-Week Data. [2020]

3. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of dolutegravir/rilpivirine in real-world clinical practice. GeSIDA study 1119. [2023]

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

Therapeutic drug monitoring and virological response at week 48 in a cohort of HIV-1-infected patients switching to dolutegravir/rilpivirine dual maintenance therapy (ANRS-MIE-BIRIDER study). [2023]

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

Effectiveness, Safety, and Costs of a Treatment Switch to Dolutegravir Plus Rilpivirine Dual Therapy in Treatment-Experienced HIV Patients. [2020]

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

Safety and Efficacy of Dolutegravir Plus Rilpivirine in Treatment-Experienced HIV-Infected Patients: The DORIVIR Study. [2020]

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

Dolutegravir-Rilpivirine, Dual Antiretroviral Therapy for the Treatment of HIV-1 Infection. [2020]