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Pharmacokinetics, Safety, and Efficacy of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Disoproxil Fumarate Single Tablet Regimen (STR) in Adolescents

20 luglio 2018 aggiornato da: Gilead Sciences

A Phase 2/3, Open-Label Study of the Pharmacokinetics, Safety, and Antiviral Activity of the Elvitegravir/ Cobicistat/Emtricitabine/Tenofovir Disoproxil Fumarate Single Tablet Regimen (STR) in HIV-1 Infected Antiretroviral Treatment-Naive Adolescents

The primary objectives of this study are to evaluate the steady-state pharmacokinetics (PK) and confirm the dose of the elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (EVG/COBI/FTC/TDF) single-tablet regimen (STR) (Part A) and to evaluate the safety and tolerability of EVG/COBI/FTC/TDF STR through Week 48 (Part B) in HIV-1 infected, antiretroviral (ARV) treatment-naive adolescents.

A total of 50 adolescent participants (12 to < 18 years of age) will be enrolled to receive EVG/COBI/FTC/TDF as follows:

  • Part A: Twelve to 16 eligible participants will be enrolled to evaluate steady-state PK, and confirm the dose, with the intent to enroll at least 4 participants 12 to < 15 and at least 4 participants 15 to < 18 years of age.
  • Part B: Following confirmation of EVG exposure in at least 12 participants from Part A, 34 to 38 participants in addition to those enrolled in Part A will be enrolled to evaluate the safety, tolerability, and antiviral activity of EVG/COBI/FTC/TDF STR.

Panoramica dello studio

Stato

Completato

Condizioni

Intervento / Trattamento

Tipo di studio

Interventistico

Iscrizione (Effettivo)

50

Fase

  • Fase 2
  • Fase 3

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Luoghi di studio

  • Stati Uniti
    • California
      • Oakland, California, Stati Uniti, 94609
        • East Bay AIDS Center Medical Group
    • Florida
      • Tampa, Florida, Stati Uniti, 33606
        • University of South Florida - Department of Pediatrics
    • Illinois
      • Chicago, Illinois, Stati Uniti, 60637
        • University of Chicago
    • New York
      • Bronx, New York, Stati Uniti, 10467
        • Montefiore Medical Center
      • New York, New York, Stati Uniti, 10016
        • New York University School of Medicine
    • Pennsylvania
      • Philadelphia, Pennsylvania, Stati Uniti, 19134
        • St. Christopher's Hospital for Children
    • Tennessee
      • Memphis, Tennessee, Stati Uniti, 38105
        • St. Jude Children's Research Hospital
  • Sud Africa
      • Cape Town, Sud Africa, 7925
        • Desmond Tutu HIV Research Centre
      • Dundee, Sud Africa, 3000
        • Mpati Medical Center
      • Johannesburg, Sud Africa, 2092
        • Clinical HIV Research Unit
      • Soweto, Sud Africa, 2013
        • Perinatal HIV Research Unit
      • Stellenbosch, Sud Africa, 7602
        • University of Stellenbosch
    • Gauteng
      • Johannesburg, Gauteng, Sud Africa, 2112
        • Rahima Moosa Mother and Child Hospital (Wits)
    • Kwazulu-Natal
      • Durban, Kwazulu-Natal, Sud Africa, 4001
        • Dr Latiff Private Practice
  • Tailandia
      • Bangkok, Tailandia, 10330
        • The HIV Netherlands Australia Thailand Research collaboration (HIV-NAT)
      • Bangkok, Tailandia, 10700
        • Siriraj Hospital, Mahidol University
      • Chon Buri, Tailandia, 20110
        • Queen Savang Vadhana Memorial Hospital
      • Khon Kaen, Tailandia, 40002
        • Srinakarind Hospital

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

Da 12 anni a 17 anni (Bambino)

Accetta volontari sani

No

Sessi ammissibili allo studio

Tutto

Descrizione

Key Inclusion Criteria:

  • 12 years to < 18 years of age at baseline
  • Able to give written assent prior to any screening evaluations
  • Parent or guardian able to give written informed consent prior to any screening evaluations and willing to comply with study requirements
  • Plasma HIV-1 RNA levels of ≥ 1,000 copies/mL
  • CD4+ cell count > 100 cells/µL
  • Weight ≥ 35 kg (77 lbs)
  • Screening genotype report must show sensitivity to FTC and TDF
  • Able to swallow oral tablets
  • Adequate renal function
  • Clinically normal ECG
  • Documented screening for active pulmonary tuberculosis per local standard of care within 6 months of a screening visit
  • Hepatic transaminases ≤ 5 x upper limit of normal
  • Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin
  • Individuals with a positive Hepatitis B surface antigen screening test can participate in the study, providing that alternate therapy (other than TDF) for chronic Hepatitis B infection is available as a part of local standard of care
  • Adequate hematologic function
  • Negative serum pregnancy test for all females
  • Males and females of childbearing potential must agree to utilize highly effective contraception methods while on study treatment or agree to abstain from heterosexual intercourse throughout the study period and for 30 days following the last dose of study drug
  • Males must agree to utilize a highly effective method of contraception during heterosexual intercourse throughout the study period and for 30 days following discontinuation of investigational medicinal product
  • Must be willing and able to comply with all study requirements
  • Life expectancy ≥ 1 year

Key Exclusion Criteria:

  • A new AIDS-defining condition diagnosed within the 30 days prior to screening
  • Prior treatment with any approved or investigational or experimental anti HIV-1 drug for any length of time (other than that given for prevention of mother-to-child transmission)
  • Evidence of active pulmonary or extra-pulmonary tuberculosis disease within 3 months of the screening visit
  • Anticipated to require rifamycin treatment for mycobacterial infection while participating in the study. Note: prophylactic Isoniazid (INH) therapy for latent tuberculosis (TB) treatment is allowed.
  • Individuals experiencing decompensated cirrhosis
  • Pregnant or lactating females
  • Have any serious or active medical or psychiatric illness which would interfere with treatment, assessment, or compliance with the protocol. This would include uncontrolled renal, cardiac, hematological, hepatic, pulmonary, endocrine, central nervous, gastrointestinal, vascular, metabolic, immunodeficiency disorders, active infection, or malignancy that are clinically significant or requiring treatment within 30 days prior to the study dosing.
  • Current alcohol or substance abuse that will potentially interfere with compliance
  • Have history of significant drug sensitivity or drug allergy
  • Known hypersensitivity to the study drugs, the metabolites or formulation excipients
  • Have been treated with immunosuppressant therapies or chemotherapeutic agents within 3 months of study screening or expected to receive these agents during the study
  • A history of malignancy within the past 5 years or ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous carcinoma
  • Have previously participated in an investigational trial involving administration of any investigational agent within 30 days prior to the study dosing
  • Participation in any other clinical trial without prior approval from sponsor is prohibited while participating in this trial
  • Receiving ongoing therapy with any disallowed medications, including drugs not to be used with EVG, COBI, FTC, TDF or individuals with any known allergies to the excipients of EVG/COBI/FTC/TDF STR tablets

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Trattamento
  • Assegnazione: N / A
  • Modello interventistico: Assegnazione di gruppo singolo
  • Mascheramento: Nessuno (etichetta aperta)

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Sperimentale: EVG/COBI/FTC/TDF
Participants will receive treatment for 48 weeks and then had the option to enter an Extension Phase to receive EVG/COBI/FTC/TDF until 1) the age of 18, 2) EVG/COBI/FTC/TDF becomes commercially available in the country the participant is enrolled, or 3) Gilead elects to terminate the development of EVG/COBI/FTC/TDF in that country.
Droga: EVG/COBI/FTC/TDF
150/150/200/300 mg STR administered orally once daily with food
Altri nomi:
  • Stribild®

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
For Part A, Pharmacokinetic (PK) Parameter: AUCtau of EVG
Lasso di tempo: Predose, 2, 4, 4.5, 5, 8, and 12 hours postdose on Day 10
AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
Predose, 2, 4, 4.5, 5, 8, and 12 hours postdose on Day 10
Incidence of Treatment-Emergent Serious Adverse Events (SAEs) and All Treatment-Emergent Adverse Events (AEs)
Lasso di tempo: Up to Week 48 plus 30 days
Up to Week 48 plus 30 days

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
For Part A, PK Parameter: Ctau of EVG, FTC, Tenofovir (TFV), and COBI
Lasso di tempo: Predose, 2, 4, 4.5, 5, 8, and 12 hours postdose on Day 10
Ctau is defined as the observed drug concentration at the end of the dosing interval.
Predose, 2, 4, 4.5, 5, 8, and 12 hours postdose on Day 10
For Part A, PK Parameter: Cmax of EVG, FTC, TFV, and COBI
Lasso di tempo: Predose, 2, 4, 4.5, 5, 8, and 12 hours postdose on Day 10
Cmax is defined as the maximum concentration of drug.
Predose, 2, 4, 4.5, 5, 8, and 12 hours postdose on Day 10
For Part A, PK Parameter: AUCtau of FTC, TFV, and COBI
Lasso di tempo: Predose, 2, 4, 4.5, 5, 8, and 12 hours postdose on Day 10
AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
Predose, 2, 4, 4.5, 5, 8, and 12 hours postdose on Day 10
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Weeks 24 and 48 as Defined by the FDA Snapshot Analysis
Lasso di tempo: Weeks 24 and 48
Weeks 24 and 48
Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Weeks 24 and 48 as Defined by the FDA Snapshot Analysis
Lasso di tempo: Weeks 24 and 48
Weeks 24 and 48
Change From Baseline in Plasma log10 HIV-1 RNA at Weeks 24 and 48
Lasso di tempo: Baseline; Weeks 24 and 48
Baseline; Weeks 24 and 48
Variazione rispetto al basale nella conta delle cellule CD4+ alle settimane 24 e 48
Lasso di tempo: Linea di base; Settimane 24 e 48
Linea di base; Settimane 24 e 48
Change From Baseline in CD4 Percentage at Weeks 24 and 48
Lasso di tempo: Baseline; Weeks 24 and 48
Baseline; Weeks 24 and 48

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

Gilead Sciences

Pubblicazioni e link utili

La persona responsabile dell'inserimento delle informazioni sullo studio fornisce volontariamente queste pubblicazioni. Questi possono riguardare qualsiasi cosa relativa allo studio.

Pubblicazioni generali

  • Gaur A, Fourie J, Chokephaibulkit K, Bekker L-G, Yin X, Custodio J, Bennett S, Cheng A, Quirk E. Pharmacokinetics, Efficacy and Safety of an Integrase Inhibitor-Based Single-Tablet Regimen in HIV-Infected Treatment-Naïve Adolescents. 21st Conference on Retroviruses and Opportunistic Infections (CROI). March 2014. Boston, MA, USA
  • Chokephaibulkit K, Gaur A, Fourie J, Bekker L-G, Shao Y, Custodio J, Bennett S, Cheng A, Quirk E. Safety and Efficacy of the Integrase Inhibitor-Based Stribild Single-Tablet Regimen in HIV-Infected Adolescents Through 24 Weeks of Treatment. 20th International AIDS Conference. July 2014. Melbourne, Australia
  • Porter DP, Bennett S, Quirk E, Miller MD, White KL. Lack of Emergent Resistance in HIV-1-Infected Adolescents on Elvitegravir-Based STRs. 22nd Conference on Retroviruses and Opportunistic Infections (CROI). February 2015. Seattle, WA, USA
  • Kizito H, Gaur A, Prasitsuebsai W, Rakhmanina N, Chokephaibulkit K, Fourie J, Bekker LG, Shao Y, Bennett S, Quirk E. Changes in renal laboratory markers and bone mineral density in treatment-naïve HIV-1-infected adolescents initiating INSTI-based single-tablet regimens containing tenofovir alafenamide (TAF) or tenofovir disoproxil fumarate (TDF). 8th IAS Conference on HIV Pathogenesis, Treatment & Prevention. July 2015. Vancouver, Canada

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio (Effettivo)

6 dicembre 2012

Completamento primario (Effettivo)

22 ottobre 2015

Completamento dello studio (Effettivo)

29 gennaio 2018

Date di iscrizione allo studio

Primo inviato

1 novembre 2012

Primo inviato che soddisfa i criteri di controllo qualità

1 novembre 2012

Primo Inserito (Stima)

4 novembre 2012

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

17 agosto 2018

Ultimo aggiornamento inviato che soddisfa i criteri QC

20 luglio 2018

Ultimo verificato

1 luglio 2018

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • GS-US-236-0112
  • 2015-000313-40 (Numero EudraCT)

Informazioni su farmaci e dispositivi, documenti di studio

Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti

Sì

Studia un dispositivo regolamentato dalla FDA degli Stati Uniti

No

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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