Cabotegravir + Rilpivirine for HIV Infection

(MOCHA Trial)

No longer recruiting at 26 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the optimal dosage and assess the safety of new HIV treatments in children and teens who have successfully controlled the virus with current medications. It tests different combinations of pills and long-acting injections of cabotegravir and rilpivirine to evaluate their effectiveness and how the body processes them. Participants must have been on a stable HIV treatment for at least three months and maintained low virus levels in their blood. As a Phase 1 and Phase 2 trial, this research seeks to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking HIV treatment advancements.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that long-acting injectable cabotegravir (CAB LA) is safe and generally well-tolerated. Studies have found few safety issues, though there is a chance of developing resistance to a type of HIV drug called INSTI. Most people found the CAB injections acceptable.

For long-acting injectable rilpivirine (RPV LA), studies indicate it is safe and causes few problems for most people. It is considered safe and acceptable when administered every eight weeks.

Oral cabotegravir is also safe to use. Safety data for teenagers are similar to those for adults, indicating young people handle it well.

Oral rilpivirine is safe and effective in both adults and teens with HIV, causing few side effects.

Overall, these treatments have been safe and well-tolerated in previous studies. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the treatments involving Cabotegravir and Rilpivirine because they offer a promising alternative to the standard daily oral therapies for HIV, such as combinations of antiretroviral drugs like tenofovir/emtricitabine and efavirenz. These treatments are unique due to their long-acting injectable forms, which can maintain viral suppression with just bi-monthly injections, reducing the burden of daily pill intake. Additionally, Cabotegravir and Rilpivirine work together by integrating into the virus’s replication process, preventing it from multiplying effectively. This approach could improve adherence and quality of life for those living with HIV, making these treatments a game-changer in HIV management.

What evidence suggests that this trial's treatments could be effective for HIV?

Research has shown that long-acting injectable cabotegravir and rilpivirine, studied in this trial, effectively control the HIV virus. Studies found that over 85% of participants remained on this treatment and maintained viral control 48 weeks after initiation. The trial includes different cohorts, such as those receiving both oral and injectable forms, and those receiving only the injectable forms. These combinations perform well in real-life situations, keeping the virus at very low levels, similar to daily pills. Participants using these long-acting treatments report higher satisfaction because they avoid daily medication. Overall, these treatments are promising for managing HIV and offer a convenient option for those seeking to reduce the hassle of daily medication. ^{2 6 7 8 9}

Who Is on the 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

Are You a Good Fit for This Trial?

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

Adolescent participant must have confirmed HIV-1-infection based on documented testing

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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]

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 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]

Citations

1. viivhealthcare.com viivhealthcare.com/hiv-news-and-media/news/press-releases/2024/october/real-world-studies-for-apretude/

ViiV Healthcare shows more than 99% effectiveness in real ... Findings from two real-world evidence studies (from OPERA and Trio Health cohorts) showed more than 99% effectiveness of CAB LA for PrEP in ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10090368/

Safety and efficacy of long-acting injectable cabotegravir as ... CAB-LA is highly efficacious for HIV prevention with few safety concerns. CAB-LA may lead to an increased risk of INSTI resistance.

3. viivhealthcare.com viivhealthcare.com/hiv-news-and-media/news/press-releases/2025/july/long-acting-injectables-for-hiv-at-ias-2025/

ViiV Healthcare presents new data demonstrating positive ... 24-month outcomes of cabotegravir+rilpivirine long-acting every 2 months in a real‑world setting: effectiveness, adherence to injections, and ...

4. academic.oup.com academic.oup.com/cid/article/81/3/543/8082057

Long-Acting Injectable HIV Therapy Outcomes Among ... In this real-world observational study, over 85% of PWH remained on therapy and virally suppressed 48 weeks after initiating LAI-CAB/RPV.

5. thelancet.com thelancet.com/journals/lanhiv/article/PIIS2352-3018(23)00261-8/fulltext

Efficacy and safety of long-acting cabotegravir compared ... HPTN 083 and 084 demonstrated 66% and 89% reductions in incident HIV infections for long-acting compared with daily oral PrEP in their ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36723489/

Safety and efficacy of long-acting injectable cabotegravir as ... Conclusions: CAB-LA is highly efficacious for HIV prevention with few safety concerns. CAB-LA may lead to an increased risk of INSTI resistance ...

7. thelancet.com thelancet.com/journals/lanhiv/article/PIIS2352-3018(24)00310-2/fulltext

Safety, tolerability, and acceptability of long-acting ... Long-acting injectable cabotegravir is a safe, tolerable, and acceptable option for the prevention of HIV in adolescent girls. Our study ...

8. viivhealthcare.com viivhealthcare.com/hiv-news-and-media/news/press-releases/2025/october/viiv-healthcare-clarity-study/

ViiV Healthcare's CLARITY study shows long-acting ... After a single dose of CAB LA and LEN, 69% (n=42/61) of individuals found CAB injections to be “totally or very acceptable” vs 48% (n=29/60) for ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT04692077

Study Details | NCT04692077 | Safety, Tolerability and ... This study will establish the minimum safety, tolerability and acceptability data needed to support the use of cabotegravir long-acting injection (CAB LA) in an ...