Doravirine for Pediatric HIV

Recruiting at 13 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

Trial Summary

What is the purpose of this trial?

This is a single-group, open-label, multi-site study in pediatric participants with human immunodeficiency virus type 1 (HIV-1) infection, aged 4 weeks to \<12 years and weighing \<45 kg, who are treatment-naive (TN) or have been virologically suppressed (VS) on stable combination antiretroviral therapy (cART) for ≥3 months with no history of treatment failure. The first primary objective is to evaluate the steady state pharmacokinetics (PK) of doravirine (DOR) \[MK-1439\] when given in combination with 2 nucleoside/nucleotide analog reverse transcriptase inhibitors (NRTIs) or as part of the fixed dose combination (FDC) of DOR/lamivudine (3TC)/tenofovir disproxil fumarate (TDF) in participants ≥6 to \<12 years and weighing ≥14 to \<45 kg. The second primary objective is to evaluate the safety and tolerability of DOR when given with 2 NRTIs or as part of the FDC of DOR/3TC/TDF, in participants ≥6 to 12 years and weighing ≥14 to \<45 kg, through Week 24.

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.

What data supports the effectiveness of the drug Doravirine for treating pediatric HIV?

Doravirine is effective in adults for suppressing HIV-1 when used as part of a combination therapy, and it has shown safety and effectiveness in adolescents with HIV-1. It also remains active against certain drug-resistant strains of the virus, suggesting it could be a valuable option for treating pediatric HIV. ^{1 2 3 4 5}

Is doravirine safe for use in humans?

Doravirine is generally considered safe and well-tolerated in adults with HIV-1, with fewer side effects compared to some other treatments. It has been approved in several countries and shows a favorable safety profile in clinical trials. ^{1 2 4 6 7}

How is the drug Doravirine unique for treating pediatric HIV?

Doravirine is unique because it is a new type of drug called a non-nucleoside reverse transcriptase inhibitor (NNRTI) that works by blocking a specific enzyme the HIV virus needs to multiply. It has a novel resistance pathway, meaning it can still work against some common drug-resistant strains of HIV, and it has fewer side effects and drug interactions compared to older NNRTIs. ^{1 2 4 7 8}

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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 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 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]

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, 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, 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, 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]

References

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

Doravirine: First Global Approval. [2021]

2. England 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. [2020]

3. United States 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. [2023]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Residual phenotypic susceptibility to doravirine in multidrug-resistant HIV-1 from subjects enrolled in the PRESTIGIO Registry. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Etravirine-based highly active antiretroviral therapy in HIV-1-infected paediatric patients. [2022]

6. Germany pubmed.ncbi.nlm.nih.gov

Efficacy and safety of doravirine in treatment-naive HIV-1-infected adults: a systematic review and meta-analysis. [2021]

7. Spain pubmed.ncbi.nlm.nih.gov

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

8. New Zealand 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. [2023]