HIV InfectionsPhase 1/2NCT01975012
Safety, Tolerability, Drug Interactions, and Antiviral Activity of Rilpivirine in Antiretroviral-Naive HIV-Infected Children Less Than 12 Years of Age
A Phase 1/2 study testing Rilpivirine in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID).
Trial summary
Development of tolerable and effective antiretroviral (ARV) drugs for use in children and adolescents remains a high priority. First-line therapy with non-nucleoside reverse transcriptase inhibitors (NNRTIs) has proven to be effective for HIV-1-infected infants, children, and adolescents. Read more about this study
- Who is it for?
- Ages 2 to 11 years
- Conditions the study is for
- HIV Infections
- What is being tested?
- Rilpivirine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Sep 2014to May 2018
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 11 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- A confirmed HIV-1 infection. More information on this criterion can be found in the protocol.
- Participant has never been treated with an HIV vaccine
- No evidence of prior ARV drug use with the exception of prior use of zidovudine (AZT) for up to 6 weeks to prevent mother-to-child transmission
- HIV-1 plasma viral load (VL) at screening greater than 500 HIV-1 RNA copies/mL but less than or equal to 100,000 HIV-1 RNA copies/mL (assayed by RNA polymerase chain reaction [PCR] standard specimen procedure) Note: Participants may be re-screened once only, if their baseline VL does not meet the entry criteria.
- In the judgment of the investigator, it is appropriate to initiate ARV therapy based on the participant's medical condition and taking into account guidelines for the treatment of HIV-1 infection in children
- Results from the genotypic resistance testing at screening demonstrate sensitivity to the selected NRTIs for the chosen background regimen
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- Able to swallow whole tablets (Cohort 1 initial dose only)
- Female participants who are of childbearing potential and who are engaging in sexual activity that could lead to pregnancy, must use two adequate birth control methods while on study and for 4 weeks after stopping study drug. More information on this criterion can be found in the protocol.
- Participants belonging to a cohort that failed Stage 1 Step 1 initial dose that meet the following criteria (as determined by the study team): Are able to have an adjustment in study drug dose (and the new dose would not exceed 25 mg) and appear to have room to stay within therapeutic range on the new dose
Who cannot join
- Having documented genotypic evidence of RPV resistance. More information on this criterion can be found in the protocol.
- Documented evidence of infection during breastfeeding by a mother taking NNRTI-based ART. If there are no data or no history available then the participant would be eligible as long as all other inclusion and exclusion criteria are fulfilled.
- Documented evidence of maternal NNRTI use during pregnancy. If there are no data or no history available then the participant would be eligible as long as all other inclusion and exclusion criteria are fulfilled.
- Previously documented HIV-2 infection in participant or participant's mother. If there are no data or no history available then the participant would be eligible as long as all other inclusion and exclusion criteria are fulfilled.
- Use of disallowed medication from 4 weeks prior to the entry visit or anticipated use of any disallowed medications
- A) Participant has used chronic systemic immunosuppressive agents within 30 days prior to entry or is anticipated to need chronic systemic immunosuppressive agents during the study. Short courses of systemic corticosteroids (e.g., prednisone or equivalent up to 2 mg/kg/day for less than or equal to 7 days) are permitted, as long as the use was greater than 30 days prior to entry; B) participant has used both chronic inhaled and intranasal steroids within 30 days prior to entry. Use of either inhaled or intranasal steroids are allowed.
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- Participant has any active AIDS-defining illness (Category C conditions according to the Centers for Disease Control and Prevention [CDC] revised Classification System for HIV Infection 1994), within 30 days prior to screening. Stable not currently active conditions that are not likely to interfere with safety assessments may be allowed with permission from the protocol team.
- Any active clinically significant disease or findings (other than HIV infection) during screening or medical history or physical examination that in the investigator's opinion, would compromise the outcome of the study
- Any confirmed Grade 3 or 4 laboratory toxicity according to the Division of AIDS (DAIDS) grading table at screening, except for: asymptomatic Grade 3 absolute neutrophil count decrease; asymptomatic Grade 3 platelet count decrease; asymptomatic Grade 3 total amylase, triglyceride, cholesterol elevation
- Participant has active tuberculosis and/or is being treated for tuberculosis at screening
- Participant has one or more of the following risk factors for ECG QTc prolongation:
- A confirmed prolongation of QT/QTc interval, (e.g., repeated demonstration of QTcF [Fridericia correction] interval greater than 450 ms in the screening ECG (i.e., retesting to reassess eligibility will be allowed once using an unscheduled visit during the screening period)
- Pathological Q-waves (defined as Q-wave greater than 40 ms or depth greater than 0.4-0.5 mV)
- Evidence of ventricular pre-excitation
- Electrocardiographic evidence of complete right or complete or incomplete left bundle branch block
- Evidence of second or third degree heart block
- Intraventricular conduction delay with QRS duration greater than 120 ms
- Bradycardia as defined by sinus rate less than 50 bpm
- Personal or family history of long QT syndrome
- Personal history of cardiac disease, symptomatic or asymptomatic arrhythmias, with the exception of sinus arrhythmia
- Syncopal episodes
- Risk factors for Torsade de Pointes (e.g., heart failure, hypokalemia)
- Participant's family is unlikely to adhere to the study procedures, keep appointments, or is planning to relocate to a non-IMPAACT study site during the study
- Hepatitis B virus surface antigen (HBsAg) positive or hepatitis C virus (HCV) antibody positive
- Any history of malignancy
- Participant enrolled in another clinical trial of an investigational agent or experimental vaccine or a compound or device which is not commercially available
- Any history of adrenal insufficiency
- Pregnancy or breastfeeding if of childbearing potential
About this study
Official title: A Phase I/II, Open-Label Trial to Evaluate the Safety, Tolerability, Pharmacokinetics and Antiviral Activity of Rilpivirine in Antiretroviral Naive HIV-1 Infected Children, < 12 Years of Age
Development of tolerable and effective antiretroviral (ARV) drugs for use in children and adolescents remains a high priority. First-line therapy with non-nucleoside reverse transcriptase inhibitors (NNRTIs) has proven to be effective for HIV-1-infected infants, children, and adolescents. This study will evaluate the safety, effectiveness, and dosing levels of the NNRTI rilpivirine (RPV) when given with two other ARV drugs in treatment-naive, HIV-1-infected children less than 12 years of age.
Read the detailed description
This study will enroll HIV-1-infected children less than 12 years of age who are naive to antiretroviral therapy (ART) (have never taken ARV drugs). Study participants will be assigned to 1 of 2 cohorts based on age. Cohort 1 will include children at least 6 years of age to less than 12 years of age. Cohort 2 will include children at least 2 years of age to less than 6 years of age. Each cohort will consist of two stages: Stage 1 and Stage 2. Stage 1 will be the initial dose finding stage. Participants will begin treatment with daily RPV and 2 nucleoside reverse transcriptase inhibitors (NRTIs). The 2 NRTIs will be selected by the site investigator but will not be provided through the study. This stage of the study will involve intense pharmacokinetic (PK) sampling to evaluate the safety, tolerability, and antiviral activity of RPV, which will allow for the selection of an RPV dose to use in Stage 2 of the study. Participants in both cohorts will remain on RPV-based therapy for up to 48 weeks.
Study enrollment will begin with Cohort 1. Once data from Cohort 1 has been reviewed and an RPV dose has been approved, enrollment for Cohort 2 will begin.
Study participation will include at least 12 study visits over 48 weeks. Participants who complete 48 weeks of RPV treatment and are benefiting from the drug will continue on the study and receive RPV as part of a long-term safety follow-up for a minimum of 4 additional years. Study visits in this stage of the study will occur every 24 weeks.
At most visits, participants will give a medical history and undergo a physical exam, blood collection, and urine collection. At some visits, participants will also undergo an electrocardiogram (ECG), adrenocorticotropic hormone (ACTH) stimulation test (consisting of blood collection and an injection of ACTH), and determination of the participant's stage of sexual development.
- Conditions
- HIV Infections
- Being tested
- Rilpivirine
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RilpivirineDrug
Also called RPV, TMC278, Edurant
For Cohort 1, Stage 1: RPV will be given orally as a 25-mg film-coated tablet (or for dosing in younger children, as granules [2.5 mg/g]) each day with a meal.
For Cohort 1, Stage 2: The dose of RPV will be determined once Cohort 1, Stage 1 data are available.
For Cohort 2: The dose of RPV will be determined once Cohort 1 data are available.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1: 6 to less than 12 years of age | Experimental | Participants in this arm will be at least 6 but younger than 12 years of age; they will receive the study drug RPV together with 2 other NRTIs. Receives: Drug: Rilpivirine |
| Cohort 2: 2 to less than 6 years of age | Experimental | Participants in this arm will be at least 2 but younger than 6 years of age; they will receive the study drug RPV together with 2 other NRTIs. Receives: Drug: Rilpivirine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Failure to meet PK guidelines
Main PK parameters include the area under the plasma concentration-time curve over 24 hours (AUC24h) and the maximum observed plasma concentration (Cmax)
Measured: Measured through Week 48
Toxicity endpoint: termination from treatment due to a suspected adverse drug reaction (SADR)
Measured: Measured through Week 24
Toxicity endpoint: adverse events (AEs) or laboratory toxicities of Grade 3 or higher severity judged to be at least possibly attributable to the study medication
Measured: Measured through Week 24
Toxicity endpoint: death
Measured: Measured through Week 24
Secondary outcomes (8)
AEs or laboratory toxicities of Grade 3 or higher severity judged to be at least possibly attributable to the study medications
Measured: Measured through Week 48
Adverse events meeting the International Conference on Harmonisation (ICH) seriousness criteria
Measured: Measured through participant's last study visit (through Week 48 or, for participants in long-term safety follow-up, through Week 240)
Treatment discontinued due to toxicity or virologic failure
Measured: Measured through participant's last study visit (through Week 48 or, for participants in long-term safety follow-up, through Week 240)
Failure to suppress plasma HIV RNA to less than 400 copies/mL (confirmed within 2 to 4 weeks)
Measured: Measured at Week 24 and Week 48
Failure to achieve undetectable plasma HIV RNA (less than 40 copies/mL on Abbott RealTime HIV-1 assay, confirmed within 2 to 4 weeks)
Measured: Measured at Week 24 and Week 48
Virologic outcome as per Snapshot and time to loss of virologic response (TLOVR)
Measured: Measured at Week 24 and Week 48
Sustained decline in absolute CD4 percent of greater than 5% any time after 12 weeks of therapy
Measured: Measured through Week 48
Long-term safety (AEs, toxicities of Grade 3 or higher severity, or deaths at least possibly related to treatment) after 48 weeks
Measured: Measured through Week 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 2013 (estimated)
- Study startSep 2014
- Primary completionMay 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Sponsor
- Investigators
- Ann Melvin, MD, MPH, Study chair, Seattle Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01975012
- Sponsor's protocol ID
- P1111
- Other IDs
- 11902
- Status last verified
- Oct 2021
- First submitted
- 28 Oct 2013
- Last updated
- 1 Nov 2021
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 1 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II, Open-Label Trial to Evaluate the Safety, Tolerability, Pharmacokinetics and Antiviral Activity of Rilpivirine in Antiretroviral Naive HIV-1 Infected Children, < 12 Years of Age
- ClinicalTrials.gov ID
- NCT01975012
- Acronym / sponsor ID
- P1111
- Conditions
- HIV Infections
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- Sep 2014
- Primary completion
- May 2018 (estimated)
- First posted
- 4 Nov 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Development of tolerable and effective antiretroviral (ARV) drugs for use in children and adolescents remains a high priority. First-line therapy with non-nucleoside reverse transcriptase inhibitors (NNRTIs) has proven to be effective for HIV-1-infected infants, children, and adolescents. This study will evaluate the safety, effectiveness, and dosing levels of the NNRTI rilpivirine (RPV) when given with two other ARV drugs in treatment-naive, HIV-1-infected children less than 12 years of age.
Detailed description
This study will enroll HIV-1-infected children less than 12 years of age who are naive to antiretroviral therapy (ART) (have never taken ARV drugs). Study participants will be assigned to 1 of 2 cohorts based on age. Cohort 1 will include children at least 6 years of age to less than 12 years of age. Cohort 2 will include children at least 2 years of age to less than 6 years of age. Each cohort will consist of two stages: Stage 1 and Stage 2. Stage 1 will be the initial dose finding stage. Participants will begin treatment with daily RPV and 2 nucleoside reverse transcriptase inhibitors (NRTIs). The 2 NRTIs will be selected by the site investigator but will not be provided through the study. This stage of the study will involve intense pharmacokinetic (PK) sampling to evaluate the safety, tolerability, and antiviral activity of RPV, which will allow for the selection of an RPV dose to use in Stage 2 of the study. Participants in both cohorts will remain on RPV-based therapy for up to 48 weeks.
Study enrollment will begin with Cohort 1. Once data from Cohort 1 has been reviewed and an RPV dose has been approved, enrollment for Cohort 2 will begin.
Study participation will include at least 12 study visits over 48 weeks. Participants who complete 48 weeks of RPV treatment and are benefiting from the drug will continue on the study and receive RPV as part of a long-term safety follow-up for a minimum of 4 additional years. Study visits in this stage of the study will occur every 24 weeks.
At most visits, participants will give a medical history and undergo a physical exam, blood collection, and urine collection. At some visits, participants will also undergo an electrocardiogram (ECG), adrenocorticotropic hormone (ACTH) stimulation test (consisting of blood collection and an injection of ACTH), and determination of the participant's stage of sexual development.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort 1: 6 to less than 12 years of age | Experimental | Drug: RilpivirineParticipants in this arm will be at least 6 but younger than 12 years of age; they will receive the study drug RPV together with 2 other NRTIs. |
| Cohort 2: 2 to less than 6 years of age | Experimental | Drug: RilpivirineParticipants in this arm will be at least 2 but younger than 6 years of age; they will receive the study drug RPV together with 2 other NRTIs. |
Who may qualify
- Ages
- 2 to 11 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (9 listed)
- A confirmed HIV-1 infection. More information on this criterion can be found in the protocol.
- Participant has never been treated with an HIV vaccine
- No evidence of prior ARV drug use with the exception of prior use of zidovudine (AZT) for up to 6 weeks to prevent mother-to-child transmission
- HIV-1 plasma viral load (VL) at screening greater than 500 HIV-1 RNA copies/mL but less than or equal to 100,000 HIV-1 RNA copies/mL (assayed by RNA polymerase chain reaction [PCR] standard specimen procedure) Note: Participants may be re-screened once only, if their baseline VL does not meet the entry criteria.
- In the judgment of the investigator, it is appropriate to initiate ARV therapy based on the participant's medical condition and taking into account guidelines for the treatment of HIV-1 infection in children
Key exclusion criteria (28 listed)
- Having documented genotypic evidence of RPV resistance. More information on this criterion can be found in the protocol.
- Documented evidence of infection during breastfeeding by a mother taking NNRTI-based ART. If there are no data or no history available then the participant would be eligible as long as all other inclusion and exclusion criteria are fulfilled.
- Documented evidence of maternal NNRTI use during pregnancy. If there are no data or no history available then the participant would be eligible as long as all other inclusion and exclusion criteria are fulfilled.
- Previously documented HIV-2 infection in participant or participant's mother. If there are no data or no history available then the participant would be eligible as long as all other inclusion and exclusion criteria are fulfilled.
- Use of disallowed medication from 4 weeks prior to the entry visit or anticipated use of any disallowed medications
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RilpivirineAlso: RPV, TMC278, EdurantFor Cohort 1, Stage 1: RPV will be given orally as a 25-mg film-coated tablet (or for dosing in younger children, as granules [2.5 mg/g]) each day with a meal. For Cohort 1, Stage 2: The dose of RPV will be determined once Cohort 1, Stage 1 data are available. For Cohort 2: The dose of RPV will be determined once Cohort 1 data are available. | Drug | Cohort 1: 6 to less than 12 years of age, Cohort 2: 2 to less than 6 years of age |
Primary outcome
Failure to meet PK guidelines
Time frame: Measured through Week 48
Main PK parameters include the area under the plasma concentration-time curve over 24 hours (AUC24h) and the maximum observed plasma concentration (Cmax)
Toxicity endpoint: termination from treatment due to a suspected adverse drug reaction (SADR)
Time frame: Measured through Week 24
Toxicity endpoint: adverse events (AEs) or laboratory toxicities of Grade 3 or higher severity judged to be at least possibly attributable to the study medication
Time frame: Measured through Week 24
Toxicity endpoint: death
Time frame: Measured through Week 24
8 secondary outcomes
AEs or laboratory toxicities of Grade 3 or higher severity judged to be at least possibly attributable to the study medications
Time frame: Measured through Week 48
Adverse events meeting the International Conference on Harmonisation (ICH) seriousness criteria
Time frame: Measured through participant's last study visit (through Week 48 or, for participants in long-term safety follow-up, through Week 240)
Treatment discontinued due to toxicity or virologic failure
Time frame: Measured through participant's last study visit (through Week 48 or, for participants in long-term safety follow-up, through Week 240)
Failure to suppress plasma HIV RNA to less than 400 copies/mL (confirmed within 2 to 4 weeks)
Time frame: Measured at Week 24 and Week 48
Failure to achieve undetectable plasma HIV RNA (less than 40 copies/mL on Abbott RealTime HIV-1 assay, confirmed within 2 to 4 weeks)
Time frame: Measured at Week 24 and Week 48
Virologic outcome as per Snapshot and time to loss of virologic response (TLOVR)
Time frame: Measured at Week 24 and Week 48
Sustained decline in absolute CD4 percent of greater than 5% any time after 12 weeks of therapy
Time frame: Measured through Week 48
Long-term safety (AEs, toxicities of Grade 3 or higher severity, or deaths at least possibly related to treatment) after 48 weeks
Time frame: Measured through Week 48
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Nov 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ann Melvin, MD, MPH study chair
Seattle Children's Hospital
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Rilpivirine in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID).
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 1 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Failure to meet PK guidelines (time frame: Measured through Week 48). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Nov 2021.