Cabotegravir + Rilpivirine for HIV Infection

(MOCHA Trial)

Recruiting at 25 trial locations

Age: < 18

Sex: Any

Trial Phase: Phase 1 & 2

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

Must be taking: Antiretrovirals

Must not be taking: Protease inhibitors

Disqualifiers: Cardiac disease, Tuberculosis, Hepatitis, 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: Unknown

168 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it requires that participants have been on a stable antiretroviral therapy (cART) regimen for at least 3 months before joining. This suggests you may need to continue your current HIV medications.

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

Research shows that the long-acting injectable combination of cabotegravir and rilpivirine is as effective as daily oral therapy in maintaining HIV-1 viral suppression over several years. Studies also indicate that patients find the injections acceptable, even with some injection-site reactions. ^{1 2 3 4 5}

Is the combination of long-acting cabotegravir and rilpivirine safe for humans?

The combination of long-acting cabotegravir and rilpivirine has been studied for up to 5 years and is generally considered safe, though some people experience injection-site reactions (like pain or swelling where the shot is given). ^{1 2 3 4 5}

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

Cabotegravir and Rilpivirine are unique because they are long-acting injectable drugs that can be administered every 4 to 8 weeks, offering an alternative to daily oral pills. This can be particularly beneficial for people who have difficulty adhering to daily medication schedules. ^{1 2 4 6 7}

What is the purpose of this trial?

This trial tests new HIV medications in pill and injection forms for children and teens. The medications work by stopping the virus from growing.

Research Team

Carolyn Bolton Moore, MSc, MBBCh

Principal Investigator

Centre for Infectious Disease Research in Zambia/University of Alabama Birmingham

Aditya H. Gaur, MD

Principal Investigator

St. Jude Children's Research Hospital

Eligibility Criteria

This trial is for HIV-infected children and adolescents aged 12 to less than 18 years, weighing at least 35 kg (77 lbs), with a BMI ≤31.5 kg/m^2, who have been on stable antiretroviral therapy for at least three months. Participants must have suppressed viral loads and be able to follow the study schedule. Those with certain medical conditions or taking disallowed medications cannot join.

Inclusion Criteria

I have been on the same HIV treatment for at least 3 months.

Participants enrolling into Cohort 1 must have completed all scheduled product injections and Week 16 visit in Cohort 1 Step 2

My BMI is 31.5 or lower.

Exclusion Criteria

I am a teenager on specific HIV treatments or have resistance to some HIV medications.

I am a teenager who has had multiple seizures this year and may have other health issues that could affect the study.

Parents or caregivers will be excluded if they have any condition or social circumstance that may make study participation unsafe or interfere with achieving study objectives

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Cohort 1 Step 1 (Oral Phase)

Participants receive oral CAB or RPV for 4-6 weeks

4-6 weeks

Cohort 1 Step 2 (Injection Phase)

Participants receive intramuscular injections of CAB LA or RPV LA

12 weeks

Cohort 2 Step 3 (Oral Phase)

Participants receive both oral CAB and RPV for 4-6 weeks

4-6 weeks

Cohort 2 Step 4 (Injection Phase)

Participants receive intramuscular injections of CAB LA and RPV LA every 8 weeks

92 weeks

Long-term Safety Follow-up (LSFU)

Participants are monitored for long-term safety after completing the injection phase

48 weeks

Treatment Details

Interventions

• Long-Acting Injectable Cabotegravir
• Long-Acting Injectable Rilpivirine
• Oral Cabotegravir
• Oral Rilpivirine

Trial Overview The MOCHA trial is testing oral and injectable forms of Cabotegravir (CAB) and Rilpivirine (RPV) in young patients with controlled HIV infection. The goal is to find the right dosages, assess safety, acceptability, tolerability, and understand how these drugs work in the body over time.

Participant Groups

Group I: Cohort 2B: CAB LA + RPV LA Experimental Treatment 2 Interventions

Step 5: First and second injections: CAB LA administered as a 600 mg IM injection AND RPV LA administered as a 900 mg IM injection at Entry and at Week 4. Subsequent injections: starting at Week 12, CAB LA administered as a 600 mg IM injection AND RPV LA administered as 900 mg IM injection every eight weeks through Week 92 or final safety extension visit.

Group II: Cohort 2A: Oral CAB + Oral RPV and CAB LA + RPV LA Experimental Treatment 4 Interventions

Step 3: CAB administered orally as one 30 mg tablet once daily AND RPV administered orally as one 25 mg tablet once daily, beginning at the Entry visit for 4-6 weeks. Step 4: First and second injections: CAB LA administered as a 600 mg IM injection AND RPV LA administered as a 900 mg IM injection at Week 4b and at Week 8. Subsequent injections: starting at Week 16, CAB LA administered as a 600 mg IM injection AND RPV LA administered as a 900 mg IM injection every eight weeks through Week 96 or final safety extension visit.

Group III: Cohort 1R: RPV Experimental Treatment 3 Interventions

Step 1: RPV administered orally as one 25 mg tablet once daily, beginning at the Entry visit, for 4-6 weeks. Step 2 (Q4W dosing): RPV LA administered as three single IM injections four weeks apart (900 mg injection at Week 4b, 600 mg injection at Week 8, 600 mg injection at and Week 12). Step 2 (Q8W dosing): RPV LA administered as two single IM injections four weeks apart (900 mg injection at Week 4b and 900 mg injection at Week 8).

Group IV: Cohort 1C: CAB Experimental Treatment 3 Interventions

Step 1: CAB administered orally as one 30 mg tablet once daily, beginning at the Entry visit, for 4-6 weeks. Step 2 (Q4W dosing): CAB LA administered as three single intramuscular (IM) injections four weeks apart (600 mg injection at Week 4b, 400 mg injection at Week 8, and 400 mg injection at Week 12). Step 2 (Q8W dosing): CAB LA administered as two single IM injections four weeks apart (600 mg injection at Week 4b and 600 mg injection at Week 8).

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

ViiV Healthcare

Industry 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

Findings from Research

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]

In a Phase 2b study involving 97 adults living with HIV-1, the long-acting formulation of cabotegravir and rilpivirine (CAB+RPV) administered every 2 months successfully maintained virologic suppression, with no participants showing HIV-1 RNA levels above 50 copies/ml after 12 months.

The long-acting CAB+RPV treatment had a favorable safety profile, with no new safety concerns identified, and 88% of participants preferred this regimen over their previous daily oral treatment, indicating high treatment satisfaction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-acting cabotegravir and rilpivirine for HIV-1 suppression: switch to 2-monthly dosing after 5 years of daily oral therapy. Mills, A., Richmond, GJ., Newman, C., et al.[2023]

Long-acting injectable cabotegravir-rilpivirine (CAB-RPV) significantly improves viral suppression rates in people with HIV who have adherence challenges, achieving 60% suppression at 3 months compared to only 13% with standard oral treatment.

In a model projecting outcomes over 3 years, CAB-RPV combined with supportive services is expected to lead to a 44% viral suppression rate and a life expectancy of 9.4 years, outperforming both standard oral treatments and those with additional support services.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Projected Benefits of Long-Acting Antiretroviral Therapy in Nonsuppressed People With Human Immunodeficiency Virus Experiencing Adherence Barriers. Chen, W., Gandhi, M., Sax, PE., et al.[2023]

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

Long-acting intramuscular cabotegravir and rilpivirine in adults with HIV-1 infection (LATTE-2): 96-week results of a randomised, open-label, phase 2b, non-inferiority trial. [2022]

2. 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]

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

The New Era of Long-Acting Antiretroviral Therapy: When and Why to Make the Switch. [2023]

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

Long-acting cabotegravir and rilpivirine for HIV-1 suppression: switch to 2-monthly dosing after 5 years of daily oral therapy. [2023]

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

Efficacy, Safety, and Durability of Long-Acting Cabotegravir and Rilpivirine in Adults With Human Immunodeficiency Virus Type 1 Infection: 5-Year Results From the LATTE-2 Study. [2022]

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

Projected Benefits of Long-Acting Antiretroviral Therapy in Nonsuppressed People With Human Immunodeficiency Virus Experiencing Adherence Barriers. [2023]

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

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