Cabotegravir + Rilpivirine for HIV During Pregnancy

Recruiting at 7 trial locations

Overseen By Rachel Scheckter

Age: 18+

Sex: Female

Trial Phase: Phase 1 & 2

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Must be taking: Antiretrovirals

Must not be taking: Nevirapine, Anticoagulants

Disqualifiers: Hepatitis B, Hepatitis C, Tuberculosis, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 4

Duration: Throughout pregnancy

45 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a Phase I/II, multicenter, open-label, non-randomized study with four groups to characterize the pharmacokinetics and safety of Cabotegravir (CAB) and Rilpivirine (RPV) long-acting injectable (LA) during pregnancy and postpartum among people with HIV-1 viral suppression and their infants.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications. However, it mentions that participants should not have taken any prohibited medication within seven days prior to entry, except for antiviral agents that are part of their current HIV treatment. It's best to discuss your specific medications with the study team.

What data supports the effectiveness of the drug Cabotegravir + Rilpivirine for HIV during pregnancy?

Research shows that Cabotegravir and Rilpivirine, when used together as a long-acting injection, are effective in maintaining HIV suppression in adults. This combination is as effective as other oral treatments, and people generally find the injections acceptable, even though they may cause some reactions at the injection site. ^{1 2 3 4 5}

Is Cabotegravir + Rilpivirine safe for use in humans?

Cabotegravir and Rilpivirine have been shown to have a favorable safety profile in adults with HIV, with high rates of sustained virus control and positive patient feedback on convenience and tolerability. However, there is limited safety data specifically for pregnant women. ^{1 2 3 5 6}

How is the drug Cabotegravir + Rilpivirine unique for treating HIV during pregnancy?

Cabotegravir + Rilpivirine is unique because it is a long-acting injectable treatment that can be administered every 2 months, offering an alternative to daily oral medications. This can be particularly beneficial for individuals who have difficulty adhering to daily pill regimens. ^{1 2 3 4 7}

Eligibility Criteria

This trial is for pregnant individuals with HIV-1 who have managed to suppress the virus. It's open to those in any trimester and continues into the postpartum period. Participants must be on a stable antiretroviral regimen, with no plans to modify it except for participating in this study.

Inclusion Criteria

Intending to deliver at a study-associated medical facility, remain in the geographic area of the study, and attend regularly scheduled study visits

Negative hepatitis C antibody test result at screening

Has documented plasma HIV-1 RNA result less than 50 copies/mL within specified timeframes

Exclusion Criteria

Plasma HIV-1 RNA measurement greater than or equal to 200 copies/mL within specified timeframe

My seizures are not well-controlled.

Specific conditions during current or previous pregnancies

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Cabotegravir and Rilpivirine long-acting injectables every 4 or 8 weeks during pregnancy

Throughout pregnancy

Visits every 4 or 8 weeks

Postpartum Follow-up

Participants and their infants are monitored for safety and pharmacokinetics postpartum

6 months postpartum

Treatment Details

Interventions

• Cabotegravir & Rilpivirine

Trial Overview The CREATE trial is testing two long-acting injectable drugs: Cabotegravir (CAB) at doses of either 400mg or 600mg, and Rilpivirine (RPV) at doses of either 900mg or 600mg. The goal is to see how these medications work and are processed by the body during pregnancy and after birth.

Participant Groups

Group I: Q8W Switch Experimental Treatment 2 Interventions

Pregnant people between 10 0/7 and 19 4/7 weeks gestation with HIV-1 viral suppression on oral antiretroviral therapy willing to switch to an every eight week (Q8W) CAB LA + RPV LA regimen.

Group II: Q8W Continuation Experimental Treatment 2 Interventions

Pregnant people between 10 0/7 and 19 4/7 weeks gestation with HIV-1 viral suppression who were using every 8 week CAB LA + RPV LA at and since conception and are willing to continue their current CAB LA + RPV LA regimen.

Group III: Q4W Switch Experimental Treatment 4 Interventions

Pregnant people between 10 0/7 and 19 4/7 weeks gestation with HIV-1 viral suppression on oral antiretroviral therapy willing to switch to an every four week (Q4W) CAB LA + RPV LA regimen.

Group IV: Q4W Continuation Experimental Treatment 2 Interventions

Pregnant people 19 4/7 weeks gestation or less with HIV-1 viral suppression who were using every 4 week CAB LA + RPV LA at and since conception and are willing to continue their current CAB LA + RPV LA regimen.

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

Findings from Research

In a study of 25 pregnancies involving women exposed to cabotegravir and rilpivirine (CAB + RPV), there were 10 live births, indicating that these medications can be used during conception with monitored outcomes.

The plasma levels of CAB and RPV during pregnancy were similar to those found in non-pregnant women, suggesting that the pharmacokinetics of these drugs remain stable and safe during pregnancy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pregnancy outcomes and pharmacokinetics in pregnant women living with HIV exposed to long-acting cabotegravir and rilpivirine in clinical trials. Patel, P., Ford, SL., Baker, M., et al.[2023]

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]

Cabotegravir and rilpivirine, as long-acting injectable therapy for HIV-1, have shown to be non-inferior to traditional oral triple-therapy in phase II and III trials, indicating their effectiveness as a treatment option.

Patients generally accept the 4-weekly or 8-weekly injections despite some experiencing injection-site reactions, but there are still important questions regarding missed doses, drug interactions, and the therapy's efficacy across different HIV-1 subtypes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluating cabotegravir/rilpivirine long-acting, injectable in the treatment of HIV infection: emerging data and therapeutic potential. Fernandez, C., van Halsema, CL.[2020]

Long-acting injectable therapies, cabotegravir (CAB) and rilpivirine (RPV), have been shown to be as effective as traditional oral antiretroviral therapy (ART) for HIV-1, maintaining efficacy over 96 weeks in clinical trials with virologically suppressed adults.

CAB has also demonstrated effectiveness as a preexposure prophylaxis (PrEP) option, significantly reducing HIV infections compared to daily oral medication, indicating its potential for broader use in HIV prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A new paradigm for antiretroviral delivery: long-acting cabotegravir and rilpivirine for the treatment and prevention of HIV. Bares, SH., Scarsi, KK.[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 cabotegravir/rilpivirine (CAB/RPV) was effective in achieving undetectable HIV RNA levels in a patient with a history of virologic failure within just two months of treatment initiation.

The case also highlights the occurrence of immune reconstitution inflammatory syndrome (IRIS) due to Mycobacterium avium-intracellulare infection after starting CAB/RPV, indicating that while the treatment is effective, it can lead to complications in patients with underlying infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune Reconstitution Inflammatory Syndrome in Aids Patient After Successful Induction of Virological Suppression with Cabotegravir/Rilpivirine. Al-Handola, R., Chinnappan, J., Bakeer, M., et al.[2023]

References

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

Pregnancy outcomes and pharmacokinetics in pregnant women living with HIV exposed to long-acting cabotegravir and rilpivirine in clinical trials. [2023]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Efficacy, safety, and tolerability of switching to long-acting cabotegravir plus rilpivirine versus continuing fixed-dose bictegravir, emtricitabine, and tenofovir alafenamide in virologically suppressed adults with HIV, 12-month results (SOLAR): a randomised, open-label, phase 3b, non-inferiority trial. [2023]

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

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

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

Evaluating cabotegravir/rilpivirine long-acting, injectable in the treatment of HIV infection: emerging data and therapeutic potential. [2020]

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

A new paradigm for antiretroviral delivery: long-acting cabotegravir and rilpivirine for the treatment and prevention of HIV. [2023]

6. 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]

7. Italy pubmed.ncbi.nlm.nih.gov

Immune Reconstitution Inflammatory Syndrome in Aids Patient After Successful Induction of Virological Suppression with Cabotegravir/Rilpivirine. [2023]