Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 2 of 11 for:    rifapentine AND children

Tuberculosis Clinical Trials Consortium Study 35

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03730181
Recruitment Status : Not yet recruiting
First Posted : November 5, 2018
Last Update Posted : June 24, 2019
Sponsor:
Collaborators:
University of Stellenbosch
Johns Hopkins University
Sanofi
University of Cape Town
Chris Hani Baragwanath Academic Hospital
Washington D.C. Veterans Affairs Medical Center
Information provided by (Responsible Party):
Centers for Disease Control and Prevention

Brief Summary:
Hypotheses: Rifapentine (given as water-dispersible monolayer and/or fixed dose combination with isoniazid) dosing in HIV-infected and uninfected children ≤ 12 years of age with latent TB infection (LTBI) or with exposure to Mycobacterium tuberculosis (M. tuberculosis) will require higher mg/kg rifapentine dosing than adults to achieve adult- exposures which are correlated with efficacy in trials of TB prevention. Investigators further hypothesize that rifapentine will be safe and well-tolerated in HIV-infected and uninfected children who require treatment for LTBI.

Condition or disease Intervention/treatment Phase
Latent Tuberculosis Drug: Rifapentine Drug: Isoniazid Phase 1 Phase 2

  Show Detailed Description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 72 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Phase I/II Dose Finding and Safety Study of Rifapentine and Isoniazid in HIV-Infected and HIV-Uninfected Children With Latent Tuberculosis Infection
Estimated Study Start Date : September 2019
Estimated Primary Completion Date : February 2021
Estimated Study Completion Date : February 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Single Arm Rifapentine and Isoniazid
Single arm, open label and exposure-controlled. Intervention is rifapentine given in a new fixed dose combination once-weekly, in combination with isoniazid for 12 weeks, in HIV-infected and HIV-uninfected children aged 0-12 years in whom LTBI treatment is indicated. The protocol allows for parallel enrolment of children into cohorts 1 and 2, simultaneously, using a predetermined modeled initial dose for each cohort, separately. Similarly, cohorts 3 and 4 will be enrolled in parallel, using modeled doses for each cohort, based on data from cohorts 1 and 2 and historical data from TBTC trials.
Drug: Rifapentine
Rifapentine. Initial dose will be 25mg/kg. Based on interim analysis, this may be adjusted throughout the study to achieve target exposures. The standalone water-dispersible rifapentine tablet may be used to adjust the rifapentine doses, if needed.

Drug: Isoniazid
Isoniazid. 25mg/kg




Primary Outcome Measures :
  1. Rifapentine exposure among participants by median area under the curve (AUC) [ Time Frame: 12 weeks ]
    Target AUC is no more than 25% lower than, and no more than 75% higher than, the target AUC of 522 mcg*h/L. Data to be used for dose adjustments throughout the study and to create dosing algorithm for pediatric subgroups.


Secondary Outcome Measures :
  1. Number of participants with Grade 3 or 4 adverse events [ Time Frame: 24 weeks ]
    Cumulative number will be reported

  2. Proportion of participants with Grade 3 or 4 adverse events [ Time Frame: 24 weeks ]
    Cumulative proportion will be reported

  3. Number of participants who discontinue study drug due to an adverse event [ Time Frame: 12 weeks ]
    Cumulative number will be reported

  4. Proportion of participants who discontinue study drug due to an adverse event [ Time Frame: 12 weeks ]
    Cumulative proportion will be reported

  5. Estimation of rifapentine absorption rate constant (ka) from plasma drug levels [ Time Frame: 12 weeks ]
    Absorption rate constant will be estimated from plasma rifapentine blood levels, using population pharmacokinetic modeling methods. Models will be controlled for between-subject variability terms such as age and weight.

  6. Estimation of rifapentine volume of distribution (Vd) from plasma drug levels [ Time Frame: 12 weeks ]
    Volume of distribution will be estimated from plasma rifapentine blood levels, using population pharmacokinetic modeling methods. Models will be controlled for between-subject variability terms such as age and weight.

  7. Estimation of rifapentine oral clearance (Cl/F) from plasma drug levels [ Time Frame: 12 weeks ]
    Oral clearance will be estimated from plasma rifapentine blood levels, using population pharmacokinetic modeling methods. Models will be controlled for between-subject variability terms such as age and weight.

  8. Post-hoc Bayesian prediction of rifapentine and metabolite peak concentration (Cmax) [ Time Frame: 12 weeks ]
    Peak concentration will be predicted from plasma rifapentine and metabolite blood levels, using population pharmacokinetic modeling methods.

  9. Post-hoc Bayesian prediction of rifapentine and metabolite time to peak concentration (Tmax) [ Time Frame: 12 weeks ]
    Time to peak concentration will be predicted from plasma rifapentine and metabolite blood levels, using population pharmacokinetic modeling methods.

  10. Post-hoc Bayesian prediction of rifapentine and metabolite area-under-the-curve (AUC0-24) [ Time Frame: 12 weeks ]
    Area-under-the-curve will be predicted from plasma rifapentine and metabolite blood levels, using population pharmacokinetic modeling methods.

  11. Post-hoc Bayesian prediction of rifapentine and metabolite half life (t 1/2) [ Time Frame: 12 weeks ]
    Half life will be predicted from plasma rifapentine and metabolite blood levels, using population pharmacokinetic modeling methods.

  12. Palatability scores [ Time Frame: 12 weeks ]
    Using a standard validated Wong-Baker Faces tool which is a tool developed to help children communicate pain. For this outcome, the scale has been adapted to communicate like and dislike, and in-depth interviews

  13. Acceptability scores [ Time Frame: 12 weeks ]
    Using a standard validated Wong-Baker Faces tool which is a tool developed to help children communicate pain. For this outcome, the scale has been adapted to communicate like and dislike, and in-depth interviews

  14. Incidence of tuberculosis [ Time Frame: 24 weeks ]
    frequency of incident tuberculosis will be reported

  15. Estimation of isoniazid absorption rate constant (ka) from plasma drug levels [ Time Frame: 12 weeks ]
    Absorption rate constant will be estimated from plasma isoniazid blood levels, using population pharmacokinetic modeling methods. Models will be controlled for N-acetyltransferase 2 (NAT2) metabolizer genotype

  16. Estimation of isoniazid volume of distribution (Vd) from plasma drug levels [ Time Frame: 12 weeks ]
    Volume of distribution will be estimated from plasma isoniazid blood levels, using population pharmacokinetic modeling methods. Models will be controlled for N-acetyltransferase 2 (NAT2) metabolizer genotype

  17. Estimation of isoniazid oral clearance (Cl/F) from plasma drug levels [ Time Frame: 12 weeks ]
    Oral clearance will be estimated from plasma isoniazid blood levels, using population pharmacokinetic modeling methods. Models will be controlled for N-acetyltransferase 2 (NAT2) metabolizer genotype

  18. Post-hoc Bayesian prediction of isoniazid peak concentration (Cmax) [ Time Frame: 12 weeks ]
    Peak concentration will be predicted from plasma isoniazid blood levels, using population pharmacokinetic modeling methods, and accounting for N-acetyltransferase 2 (NAT2) metabolizer genotype

  19. Post-hoc Bayesian prediction of isoniazid time to peak concentration (Tmax) [ Time Frame: 12 weeks ]
    Time to peak concentration will be predicted from plasma isoniazid blood levels, using population pharmacokinetic modeling methods, and accounting for N-acetyltransferase 2 (NAT2) metabolizer genotype

  20. Post-hoc Bayesian prediction of isoniazid area-under-the-curve (AUC0-24) [ Time Frame: 12 weeks ]
    Area-under-the-curve will be predicted from plasma isoniazid blood levels, using population pharmacokinetic modeling methods, and accounting for N-acetyltransferase 2 (NAT2) metabolizer genotype

  21. Post-hoc Bayesian prediction of isoniazid half life (t 1/2) [ Time Frame: 12 weeks ]
    Half life will be predicted from plasma isoniazid blood levels, using population pharmacokinetic modeling methods, and accounting for N-acetyltransferase 2 (NAT2) metabolizer genotype



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   up to 12 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Aged 0 - 12 years
  2. Documented close (household or other close exposure) for at least an average 4 hours a day over the past 6 months to a bacteriologically confirmed adult (18 years or older) source case with pulmonary TB. The adult TB source case should have confirmed drug sensitive (sputum culture confirmed or XPERT MTB/Rif [Cepheid] positive TB and without any evidence of drug resistance, i.e., at least XPERT MTB/Rif rifampicin susceptible or an alternative molecular or phenotypic test indicating rifampicin susceptible M. tb) OR:
  3. Evidence of M. tb infection (positive TST ≥ 10 mm in HIV-uninfected and TST ≥ 5 mm in HIV-infected participants or a positive commercial interferon-gamma release assay, as defined by the manufacturer)
  4. Confirmed HIV status:

    HIV status will be confirmed by DNA PCR and Plasma HIV-RNA if the participant is <18 months of age.

    In participants ≥18 month of age HIV-ELISA testing will be completed. If any HIV test is positive in a child participant, regardless of age, the test result needs to be confirmed with a second HIV test, using HIV DNA or RNA PCR, from an independent sample.

  5. HIV-infected participants should be on an ART regimen for at least 12 weeks prior to enrolment and should be clinically stable before entering the study, regardless of CD 4 count and HIV viral load. While on study, participants must be on an efavirenz- or raltegravir-based ART regimen which should have been given for at least 14 days prior to enrolment.
  6. Caregiver (parent or legal guardian) gives written informed consent and assent from the child where applicable
  7. Weight > 2.5 kg but < 40 kg

Exclusion Criteria:

  1. Active TB disease (evidenced by: symptoms suggestive of TB, or suggestive findings on clinical examination, or suggestive chest radiographic findings, or positive mycobacterial culture/molecular TB tests -if culture/molecular testing was clinically indicated and was completed-, or currently on TB treatment for active disease).
  2. Any documented drug resistant TB (DR TB) in an identified adult source case, defined as rifampicin resistance on Xpert or any other relevant approved molecular test, or phenotypic evidence of rifampicin resistance.
  3. Receipt of a once-daily isoniazid regimen for > 30 days which was given for at least 14 consecutive days in the 30 days prior to enrolment.
  4. Hb < 10 mg/dl
  5. Weight for age z score below 2 or severe clinical malnutrition
  6. Known allergy or hypersensitivity to isoniazid or rifapentine
  7. Documented hepatic disorder including > 5 fold elevated upper limit of normal (ULN) ALT and/or bilirubin
  8. Lansky play score < 50
  9. Documentation of Hepatitis A or B infection
  10. Female adolescents who have reached menarche will not be eligible.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03730181


Contacts
Layout table for location contacts
Contact: Rosanna Boyd, MPH 4045537434 RBoyd1@cdc.gov
Contact: Barbara DeCausey, MPH 404.639.5330 dfv3@cdc.gov

Sponsors and Collaborators
Centers for Disease Control and Prevention
University of Stellenbosch
Johns Hopkins University
Sanofi
University of Cape Town
Chris Hani Baragwanath Academic Hospital
Washington D.C. Veterans Affairs Medical Center

Layout table for additonal information
Responsible Party: Centers for Disease Control and Prevention
ClinicalTrials.gov Identifier: NCT03730181     History of Changes
Other Study ID Numbers: 6993
First Posted: November 5, 2018    Key Record Dates
Last Update Posted: June 24, 2019
Last Verified: October 2018

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Rifapentine
Tuberculosis
Latent Tuberculosis
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Isoniazid
Rifampin
Antitubercular Agents
Anti-Bacterial Agents
Anti-Infective Agents
Fatty Acid Synthesis Inhibitors
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Antibiotics, Antitubercular
Leprostatic Agents
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Cytochrome P-450 CYP2B6 Inducers
Cytochrome P-450 Enzyme Inducers
Cytochrome P-450 CYP2C8 Inducers
Cytochrome P-450 CYP2C19 Inducers
Cytochrome P-450 CYP2C9 Inducers
Cytochrome P-450 CYP3A Inducers