Safety, Tolerability, Drug Interactions, and Antiviral Activity of Rilpivirine in Antiretroviral-Naive HIV-Infected Children Less Than 12 Years of Age

NCT01975012 | Withdrawn Phase 1 DMC

• 2 other identifiers: P111111902
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief 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. 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.

Conditions

HIV Infections

Outcome Measures

Primary Outcomes (4)

• 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 through Week 48

• Toxicity endpoint: termination from treatment due to a suspected adverse drug reaction (SADR)

  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 through Week 24

• Toxicity endpoint: death

  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 through Week 48

• Adverse events meeting the International Conference on Harmonisation (ICH) seriousness criteria

  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 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 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 at Week 24 and Week 48

Study Arms (2)

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.

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.

Drug: Rilpivirine

Interventions

Rilpivirine DRUG

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.

Also known as: RPV, TMC278, Edurant

Cohort 1: 6 to less than 12 years of age; Cohort 2: 2 to less than 6 years of age

Eligibility Criteria

• Age: 2 Years - 11 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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
• 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

You may not qualify if:

• Having documented genotypic evidence of RPV resistance. More information on this criterion can be found in the protocol.
• 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.
• 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

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• National Institute of Mental Health (NIMH): collaborator

MeSH Terms

Conditions

HIV Infections

Interventions

Rilpivirine

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Ann Melvin, MD, MPH

  Seattle Children's Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 28, 2013
• First Posted: November 4, 2013
• Study Start: September 1, 2014
• Primary Completion: May 1, 2018
• Last Updated: November 1, 2021

Record last verified: 2021-10