Doravirine for Pediatric HIV

Recruiting at 18 trial locations

Overseen By Toll Free Number

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: Merck Sharp & Dohme Corp.

Must be taking: Antiretrovirals

Must not be taking: Immunosuppressives, Immune modulators

Disqualifiers: Renal disease, Liver disease, Pancreatitis, others

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

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 96 weeks

84 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests doravirine, a medication for children with HIV-1. The main goal is to understand how the drug behaves in the body and assess its safety and tolerability when combined with other HIV medications. Children with HIV-1 who weigh less than 45 kg (approximately 99 lbs) and have managed their condition well on other treatments might be suitable candidates. This study helps researchers determine if doravirine could be a viable option for young patients with HIV. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group, contributing to important findings for young patients.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but it mentions that participants should not be on systemic immunosuppressive therapy or other prohibited therapies. It's best to discuss your current medications with the trial team to see if they are allowed.

Is there any evidence suggesting that doravirine is likely to be safe for pediatric patients?

Research shows that the HIV treatment doravirine is generally well-tolerated. Studies with children and teens have examined its safety and metabolism. So far, results have been positive, with no major safety concerns reported.

The FDA has approved doravirine for treating HIV in children weighing at least 35 kg (about 77 pounds), indicating a good safety record for children around this weight. For younger or lighter children, ongoing studies are investigating its use.

Overall, the available safety data suggest that doravirine is a safe option for treating HIV in children. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for HIV?

Doravirine is unique because it targets HIV-1 by inhibiting the reverse transcriptase enzyme, which the virus uses to replicate. This non-nucleoside reverse transcriptase inhibitor (NNRTI) is noteworthy for its potential to be effective in pediatric patients, as it's being evaluated in doses adjusted by weight. Researchers are excited about Doravirine because it offers a promising option that could simplify treatment regimens and improve adherence in children, which is crucial for managing HIV effectively over the long term.

What evidence suggests that doravirine might be an effective treatment for pediatric HIV?

Research has shown that doravirine effectively treats HIV-1. In earlier studies, doravirine helped 91.5% of patients maintain low virus levels (HIV-1 RNA <50 copies/mL) after 48 weeks. Another study found that 90.8% of patients using doravirine with certain other medications achieved similar success. In this trial, participants will receive doravirine combined with two NRTIs. Doravirine is also approved for children weighing at least 35 kg, demonstrating its effectiveness for younger patients. Overall, doravirine shows promise in controlling the virus in people with HIV-1. ^{4 6 7 8 9}

Who Is on the Research Team?

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Are You a Good Fit for This Trial?

This trial is for HIV-infected children from 4 weeks to under 12 years old, weighing less than 45 kg. They must be either new to treatment or have had their virus levels controlled for at least three months without any history of treatment failure. Girls who can have babies must not be pregnant, breastfeeding, and should use birth control or practice abstinence.

Inclusion Criteria

I understand the study details and agree to continue treatment as advised for up to 224 weeks.

I am not pregnant or breastfeeding, and if I can have children, I use contraception or practice abstinence.

Has completed the Week 96 visit

Exclusion Criteria

I am not taking, nor do I need, any drugs that weaken my immune system.

I have had cancer before.

I have kidney disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive DOR in combination with 2 NRTIs for 96 weeks

96 weeks

Regular visits for monitoring and PK sampling

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Extension

Participants may continue to receive DOR until it is commercially available or for up to an additional 224 weeks

Up to 224 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Doravirine

Trial Overview The study tests Doravirine (DOR), an HIV medication, in combination with two other antiretroviral drugs (NRTIs) in young patients. It aims to understand how the body processes DOR and assess its safety over a period of up to six months.

How Is the Trial Designed?

Group I: Doravirine + 2 NRTIs Experimental Treatment 2 Interventions

Participants receive DOR (3.2 mg to 100 mg based on weight) in combination with 2 NRTIs (based on local label) for 96 weeks.

Doravirine is already approved in United States, European Union for the following indications:

Approved in United States as Pifeltro for:

• HIV-1 infection

Approved in United States as Delstrigo for:

• HIV-1 infection

Approved in European Union as Delstrigo for:

• HIV-1 infection

Who Is Running the Clinical Trial?

Merck Sharp & Dohme Corp.

Lead Sponsor

Trials

2,287

Recruited

4,582,000+

Chirfi Guindo

Merck Sharp & Dohme Corp.

Chief Medical Officer

Engineering degree from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme Corp.

Chief Executive Officer since 2021

J.D. from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Merck Sharp & Dohme LLC

Lead Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Published Research Related to This Trial

Doravirine is a newly approved non-nucleoside reverse transcriptase inhibitor (NNRTI) for treating HIV-1 infection, available as both a single-agent tablet and a fixed-dose combination with other antiretroviral drugs.

It is specifically indicated for adults with no prior antiretroviral treatment and has received positive regulatory opinions in the USA and EU, highlighting its safety and efficacy for treatment-naïve patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Doravirine: First Global Approval. Deeks, ED.[2021]

In a study involving 55 adolescents with HIV-1, doravirine and the fixed-dose combination (DOR FDC) of doravirine/lamivudine/tenofovir disoproxil fumarate demonstrated effective pharmacokinetics similar to those seen in adults, indicating its potential for use in this age group.

The treatment was well-tolerated, with no serious drug-related adverse events, and 93.3% of participants maintained undetectable HIV-1 RNA levels (<40 copies/mL) after 24 weeks, showcasing its efficacy in managing HIV-1 in adolescents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, Tolerability, and Safety of Doravirine and Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate Fixed-Dose Combination Tablets in Adolescents Living With HIV: Week 24 Results From IMPAACT 2014. Melvin, AJ., Yee, KL., Gray, KP., et al.[2023]

Doravirine, a new treatment for HIV-1, is taken once daily and shows a favorable pharmacokinetic profile, with no significant impact from age, gender, or mild to moderate renal and hepatic impairments, making it suitable for diverse patient populations.

The drug has a low potential for drug-drug interactions, allowing it to be safely combined with other antiretroviral medications, although it should not be used with strong CYP3A inducers like rifampin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Pharmacokinetics of the Novel HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitor Doravirine: An Assessment of the Effect of Patient Characteristics and Drug-Drug Interactions. Khalilieh, S., Yee, KL., Sanchez, R., et al.[2023]

Doravirine, particularly at a dose of 100 mg, demonstrated the highest efficacy in treating HIV-1 among various treatment options, based on a meta-analysis of six randomized controlled trials.

While doravirine showed a good safety profile, the placebo group had the least adverse events, indicating that doravirine is a safe and well-tolerated option for initial HIV-1 therapy, comparable to other standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of doravirine in treatment-naive HIV-1-infected adults: a systematic review and meta-analysis. Afify, MA., Ahmed, IGG., Alkahtani, TA., et al.[2021]

Doravirine is a safe and effective part of antiretroviral therapy for both treatment-naive and treatment-experienced adults with HIV-1, showing no resistance after 48 weeks in virologically suppressed individuals switching to a regimen including doravirine.

Emergent drug resistance to doravirine is rare (<2%) in treatment-naive patients, and it remains effective against the common K103N resistance mutation, suggesting that resistance to doravirine-based therapies is expected to be uncommon.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmaceutical, clinical, and resistance information on doravirine, a novel non-nucleoside reverse transcriptase inhibitor for the treatment of HIV-1 infection. Pham, HT., Xiao, MA., Principe, MA., et al.[2020]

In a study of 23 multidrug-resistant pediatric patients with HIV-1, etravirine treatment led to a significant antiviral response, with 87% of patients achieving HIV-1 RNA levels below 400 copies/mL and 78% below 50 copies/mL after therapy.

The treatment was generally safe and well-tolerated, with most patients showing improved CD4 T-cell counts, although some experienced mild to moderate skin rashes and laboratory abnormalities like hypercholesterolemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Etravirine-based highly active antiretroviral therapy in HIV-1-infected paediatric patients. Briz, V., Palladino, C., Navarro, M., et al.[2022]

Doravirine, a new non-nucleoside reverse transcriptase inhibitor (NNRTI) approved for HIV treatment, has shown noninferior efficacy compared to efavirenz- and darunavir-based regimens while causing fewer adverse events in clinical trials.

It retains effectiveness against common NNRTI resistance mutations and has a favorable drug interaction profile, as it does not affect the cytochrome P450 3A4 enzyme, making it a recommended option in certain clinical situations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Doravirine: a new non-nucleoside reverse transcriptase inhibitor for the treatment of HIV infection. Talwani, R., Temesgen, Z.[2020]

Doravirine shows promise as a treatment option for multidrug-resistant HIV-1, with 23% of cases demonstrating full susceptibility, compared to only 18% for etravirine and 5% for rilpivirine, based on a study of 22 participants with a long history of HIV treatment.

The study found that higher numbers of NNRTI mutations in the virus correlated with increased resistance to doravirine, but doravirine's effectiveness can still be predicted accurately using the Stanford HIVdb algorithm.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Residual phenotypic susceptibility to doravirine in multidrug-resistant HIV-1 from subjects enrolled in the PRESTIGIO Registry. Saladini, F., Giammarino, F., Maggiolo, F., et al.[2023]

Citations

1. rsc.niaid.nih.gov rsc.niaid.nih.gov/sites/default/files/Doravirine%20%28Pifeltro%29%20PI_dated%20June%202022.pdf

Doravirine (Pifeltro) PI_dated June 2022.pdf The safety and efficacy of PIFELTRO for the treatment of HIV-1 infection have been established in pediatric patients weighing at least 35 kg [see Indications ...

2. merckconnect.com merckconnect.com/doravirine/pifeltro-clinical-efficacy/

Clinical Efficacy Data for PIFELTRO® (doravirine) Tablets 20% of patients at baseline had HIV-1 RNA >100,000 copies/mL. PIFELTRO showed consistent virologic suppression regardless of baseline viral load. View DRIVE- ...

3. clinicalinfo.hiv.gov clinicalinfo.hiv.gov/en/guidelines/pediatric-arv/doravirine?view=full

Pediatric Antiretroviral Drug Information - Doravirine | NIH Long-term efficacy in the extension arm at Week 144 showed virologic suppression (HIV RNA<50 copies/mL) in 80.1% of ISG (351 out of 438) and 83.7% of DSG (175 ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11302240/

Long-term effectiveness, safety, and tolerability of doravirine in ... At week 48, the effectiveness of DOR plus ABV/3TC by ITT was 90.8% (CI95, 88.0–93.6), better than with TFV/FTC [73.3% (66.7–79.9); P = 0.003].

5. merck.com merck.com/news/merck-announces-positive-data-from-phase-3-trials-that-show-the-investigational-once-daily-oral-two-drug-regimen-of-doravirine-islatravir-dor-isl-maintained-hiv-1-viral-suppression-at-week-48/

Merck Announces Positive Data from Phase 3 Trials that ... At Week 48, 91.5% of participants who switched to DOR/ISL maintained viral suppression (HIV-1 RNA <50 copies/mL) compared to 94.2% of ...

6. clinicalinfo.hiv.gov clinicalinfo.hiv.gov/en/guidelines/pediatric-arv/doravirine

Pediatric Antiretroviral Drug Information - Doravirine | NIH In the FDA snapshot analysis, HIV RNA <50 copies/mL was maintained in 457 (83%) of 550 participants who continued DOR-based ART and 404 (80%) of 502 ...

7. rsc.niaid.nih.gov rsc.niaid.nih.gov/sites/default/files/Doravirine%20%28Pifeltro%29%20PI%20dated%20Jan%202022.pdf

Doravirine (Pifeltro) PI dated Jan 2022.pdf The safety and efficacy of PIFELTRO for the treatment of HIV-1 infection have been established in pediatric patients weighing at least 35 kg [see Indications ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT03332095

NCT03332095 | Evaluating the Pharmacokinetics, Safety, ... This study evaluated the pharmacokinetics (PK), safety, and tolerability of DOR and DOR/3TC/TDF in HIV-1-infected children and adolescents.

9. ema.europa.eu ema.europa.eu/en/documents/variation-report/delstrigo-h-c-ws2065-epar-assessment-report-variation_en.pdf

CHMP extension of indication variation assessment report The main concern here is with regards to lack of long-term tenofovir safety data; with a limited paediatric program, the PK should be well ...