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Study of Grazoprevir (MK-5172) and Elbasvir (MK-8742) in Japanese Participants With Chronic Hepatitis C (MK-5172-058)

23 agosto 2018 aggiornato da: Merck Sharp & Dohme LLC

A Phase II, Randomized Clinical Trial to Study the Safety, Tolerability, and Efficacy of the Combination Regimen of MK-5172 and MK-8742 in Japanese Subjects With Chronic Hepatitis C and a Phase III, Randomized Placebo-Controlled Clinical Trial to Study the Safety, Tolerability, and Efficacy of the Combination Regimen of MK-5172 and MK-8742 in Japanese Subjects With Chronic Hepatitis C

This is a two-part study of grazoprevir (MK-5172) + elbasvir (MK-8742) in Japanese participants with chronic hepatitis C virus (HCV) genotype 1 (GT1). Part I is a dose-finding study; in Part II, participants will be randomly assigned to receive grazoprevir at the dose determined in Part I in combination with elbasvir. The primary study hypothesis is that the percentage of treatment-naïve participants in the Immediate Treatment Arm of Part II who achieve sustained viral response at 12 weeks after the end of all treatment (SVR12) will be greater than the reference rate of 75%. A separate study arm for cirrhotic participants will also be included in Part II; these participants will receive grazoprevir at the determined dose in combination with elbasvir.

Panoramica dello studio

Stato

Completato

Condizioni

Intervento / Trattamento

Descrizione dettagliata

In Part 1, HCV GT1 participants are randomized into one of two arms: 50 mg grazoprevir plus 50 mg elbasvir for 12 weeks during the double blinded (DB) period followed by 24 weeks of follow-up (FU) during an open-label (OL) period [Arm 1]; or 100 mg grazoprevir plus 50 mg elbasvir for 12 weeks during the DB followed by 24 weeks of FU during the OL [Arm 2]. Unblinding will occur after all participants complete FU Week 4 at which time the grazoprevir dose will be selected.

In Part 2, non-cirrhotic HCV GT1 participants and GT1 participants with compensated liver cirrhosis all receive the selected dose of grazoprevir (50 mg or 100 mg from Part 1) with 50 mg elbasvir for 12 weeks. Non-cirrhotic GT1 participants are randomized to receive either a) 12 weeks of active treatment immediately during the DB with 24 weeks of FU in the OL [Arm 1/Immediate Arm] or b) placebo for 12 weeks with 4 weeks of follow-up during the DB followed by 12 weeks of active treatment and 24 weeks of follow-up during the OL [Arm 2/Deferred Arm]. All cirrhotic participants [Arm 3/Cirrhotic] receive the selected dose immediately for 12 weeks during the DB with 24 weeks of FU during the OL.

Safety analyses for Part 1 and Part 2 arms will focus on the 12 week treatment phase plus the first 4 FU weeks. For the Part 2 Deferred Arm this will include the initial 12 week placebo treatment and first 4 weeks of FU. Efficacy analyses for Parts 1 and 2 will evaluate active treatment only (Weeks 1-12 for all arms except for Part 2 Deferred Arm which is weeks 16-28).

Part 1:

50 mg grazoprevir + 50 mg elbasvir treatment for 12 weeks, 24 weeks follow-up (Arm 1) 100 mg grazoprevir + 50 mg elbasvir treatment for 12 weeks, 24 weeks follow-up (Arm 2)

Part 2:

Selected dose of grazoprevir + 50 mg elbasvir treatment for 12 weeks, 24 weeks follow-up (Arm 1/Immediate) Placebo treatment for 12 weeks, 4 weeks follow-up, selected dose of grazoprevir + 50 mg elbasvir treatment for 12 weeks, 24 weeks follow-up (Arm 2/Deferred) Selected dose of grazoprevir + 50 mg elbasvir treatment for 12 weeks, 24 weeks follow-up (Arm 3/Cirrhotic)

Tipo di studio

Interventistico

Iscrizione (Effettivo)

399

Fase

  • Fase 2
  • Fase 3

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 20 anni a 80 anni (Adulto, Adulto più anziano)

Accetta volontari sani

No

Sessi ammissibili allo studio

Tutto

Descrizione

Inclusion Criteria:

  • Has documented chronic Japanese HCV genotype (GT) 1 with no evidence of non-typeable or mixed GT infection
  • Is treatment-naïve, or intolerant or non-responder to prior anti-HCV interferon (IFN)-based treatment without direct acting antiviral (DAA) therapy, prior IFN-based treatment with DAA therapy, or prior DAA therapy
  • Agrees to the use of contraception if a female of reproductive potential

Exclusion Criteria:

  • Has evidence of decompensated liver disease manifested by the presence of or history of ascites, esophageal or gastric variceal bleeding, hepatic encephalopathy or other signs or symptoms of advanced liver disease
  • Is coinfected with hepatitis B virus or human immunodeficiency virus (HIV)
  • Has a history of malignancy ≤5 years prior to signing informed consent except for adequately treated basal cell or squamous cell skin cancer or carcinoma in situ
  • Has cirrhosis and liver imaging within 6 months of Day 1 showing evidence of hepatocellular carcinoma (HCC) or is under evaluation for HCC (Part 2 only)
  • Has clinically-relevant drug or alcohol abuse within 12 months of screening
  • Is a female and is pregnant or breast-feeding, or expecting to conceive or donate eggs from Day 1 and continue throughout treatment and follow-up (or longer if dictated by local regulations)
  • Has any of the following conditions:
  • Organ transplants (including hematopoietic stem cell transplants) other than cornea and hair
  • Poor venous access
  • History of gastric surgery (e.g., stapling, bypass) or subject with a history of malabsorption disorders (e.g., celiac sprue disease)
  • History of a medical/surgical condition that resulted in hospitalization within the 3 months prior to enrollment, other than for minor elective procedures
  • Medical/surgical conditions that may result in a need for hospitalization during the period of the study
  • Any medical condition requiring, or likely to require, chronic systemic administration of corticosteroids, TNF antagonists, or other immunosuppressant drugs during the course of the trial
  • Has chronic hepatitis not caused by HCV, including but not limited to nonalcoholic steatohepatitis (NASH), drug-induced hepatitis, and autoimmune hepatitis

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: Randomizzato
  • Modello interventistico: Assegnazione parallela
  • Mascheramento: Doppio

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Sperimentale: Part 1 Grazoprevir 50 mg + Elbasvir
Non-cirrhotic participants take 50 mg grazoprevir in combination with 50 mg elbasvir by mouth (p.o.) once daily (q.d.) for 12 weeks during the blinded period of Part 1 and are followed-up for 24 weeks during the open-label period of Part 1.
Droga: Grazoprevir
One or two 50 mg tablets (depending on randomization) taken orally once daily for 12 weeks.
Droga: Elbasvir
One 50 mg tablet taken orally once daily for 12 weeks.
Droga: Placebo to Grazoprevir
One tablet of placebo matched to grazoprevir, taken orally once daily for 12 weeks.
Sperimentale: Part 1 Grazoprevir 100 mg + Elbasvir
Non-cirrhotic participants take 100 mg grazoprevir in combination with 50 mg elbasvir p.o. q.d. for 12 weeks during the blinded period of Part 1 and are followed-up for 24 weeks during the open-label period of Part 1.
Droga: Grazoprevir
One or two 50 mg tablets (depending on randomization) taken orally once daily for 12 weeks.
Droga: Elbasvir
One 50 mg tablet taken orally once daily for 12 weeks.
Sperimentale: Part 2 Non-cirrhotic Immediate: Grazoprevir + Elbasvir
Non-cirrhotic participants take grazoprevir (50 mg or 100 mg dose selected from Part I) and 50 mg elbasvir p.o. q.d. for 12 weeks during the blinded period of Part 2 and are followed-up for 24 weeks during the open-label period of Part 2.
Droga: Grazoprevir
One or two 50 mg tablets (depending on randomization) taken orally once daily for 12 weeks.
Droga: Elbasvir
One 50 mg tablet taken orally once daily for 12 weeks.
Comparatore placebo: Part 2 Non-cirrhotic Deferred: Placebo► Grazoprevir + Elbasvir
Non-cirrhotic participants take dose-matched placebo p.o. q.d. for 12 weeks during the blinded period of Part 2 followed by a 4-week follow-up. Afterwards, participants take grazoprevir (50 mg or 100 mg dose selected from Part I) and 50 mg elbasvir p.o. q.d. for 12 weeks and are followed-up for 24 weeks during the open-label period of Part 2.
Droga: Grazoprevir
One or two 50 mg tablets (depending on randomization) taken orally once daily for 12 weeks.
Droga: Elbasvir
One 50 mg tablet taken orally once daily for 12 weeks.
Droga: Placebo to Grazoprevir
One tablet of placebo matched to grazoprevir, taken orally once daily for 12 weeks.
Droga: Placebo to Elbasvir
One tablet of placebo matched to elbasvir, taken orally once daily for 12 weeks.
Sperimentale: Part 2 Cirrhotic: Grazoprevir + Elbasvir
Cirrhotic participants take grazoprevir (50 mg or 100 mg dose selected from Part 1) and 50 mg elbasvir p.o. q.d. for 12 weeks during the blinded period of Part 2, and are followed-up for 24 weeks during the open-label period of Part 2.
Droga: Grazoprevir
One or two 50 mg tablets (depending on randomization) taken orally once daily for 12 weeks.
Droga: Elbasvir
One 50 mg tablet taken orally once daily for 12 weeks.

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Part 2: Percentage of Treatment-naïve Participants in the Immediate Treatment Arm Achieving Sustained Viral Response at 12 Weeks After The End of All Treatment (SVR12)
Lasso di tempo: 12 weeks after end of all therapy in Part 2 (Study Week 24 of Part 2)
Blood was drawn from each participant to assess Hepatitis C Virus ribonucleic acid (HCV RNA) plasma levels using the Roche COBAS® Taqman quantitative reverse transcription-polymerase chain reaction (RT-PCR) assay, v2.0, which had a lower limit of quantification (LLoQ) of 1.2 Log IU/mL (15 IU/mL) and a lower limit of detection (LLoD) below 15 IU/ml (no specific value). SVR12 was defined as undetectable HCV RNA (target not detected) at 12 weeks after the end of all study therapy. The Clopper-Pearson method was used to construct 95% confidence intervals (CIs) for the SVR12 rate. The lower limit of the 95% CI was compared to the reference rate of 75%; a lower CI limit that was higher than the reference rate would confirm the primary hypothesis and indicate that that the treatment combination was efficacious. As pre-specified in the protocol, only the Immediate Treatment Arm of Part 2 (treatment naïve participants) was included in the primary efficacy analysis.
12 weeks after end of all therapy in Part 2 (Study Week 24 of Part 2)
Part 1: Percentage of Participants Experiencing an Adverse Event (AE) During Treatment and First 4 Follow-Up Weeks
Lasso di tempo: Up to 4 weeks post last dose in Part 1 (Up to total of 16 weeks)
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, was also an AE. The primary safety evaluation was limited to the initial treatment period through Follow-up Week 4 (FUWK4).
Up to 4 weeks post last dose in Part 1 (Up to total of 16 weeks)
Part 1: Percentage of Participants That Discontinued Treatment Due to an AE
Lasso di tempo: Up to Study Week 12 in Part 1
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, was also an AE. The primary safety evaluation was limited to the initial treatment period through FUWK4.
Up to Study Week 12 in Part 1
Part 2: Percentage of Participants Experiencing an AE During Initial Treatment and First 4 Follow-Up Weeks
Lasso di tempo: Up to 4 weeks following initial treatment in Part 2 (Up to total of 16 weeks)
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, was also an AE. The primary safety evaluation was limited to the initial treatment period and first 4 follow-up weeks, and the primary safety statistical analysis compared the percentage of participants with events between the Part 2 Immediate Treatment Arm and the Part 2 Deferred Treatment Arm while receiving placebo.
Up to 4 weeks following initial treatment in Part 2 (Up to total of 16 weeks)
Part 2: Percentage of Participants That Discontinued Initial Treatment Due to an AE
Lasso di tempo: Up to Study Week 12 in Part 2
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, was also an AE. The primary safety evaluation was limited to the initial treatment period and first 4 follow-up weeks, and the primary safety statistical analysis compared the percentage of participants with events between the Part 2 Immediate Treatment Arm and the Part 2 Deferred Treatment Arm while receiving placebo.
Up to Study Week 12 in Part 2

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Part 1: Percentage of Participants Achieving Undetectable HCV RNA Over Time
Lasso di tempo: Part 1 Treatment Weeks (TW)2, TW4, TW12, End of Treatment (EOT), FUWK4, FUWK12, FUWK24
Blood was drawn from each participant to assess HCV RNA plasma levels using the Roche COBAS® Taqman quantitative RT-PCR assay, v2.0, which had a LLoQ of 1.2 Log IU/mL (15 IU/mL) and a LLoD below 15 IU/ml (no specific value). Undetectable HCV RNA was defined as HCV RNA target not detected. The percentage of participants with undetectable HCV RNA at TW2, TW4, TW12, EOT, FUWK4, FUWK12, and FUWK24 is summarized for each arm. The Clopper-Pearson method was used to construct 95% CIs for SVR rates.
Part 1 Treatment Weeks (TW)2, TW4, TW12, End of Treatment (EOT), FUWK4, FUWK12, FUWK24
Part 1: Percentage of Participants Achieving HCV RNA Below the Lower Limit of Quantitation (<LLoQ) Over Time
Lasso di tempo: Part 1 TW2, TW4, TW12, EOT, FUWK4, FUWK12, FUWK24
Blood was drawn from each participant to assess HCV RNA plasma levels using the Roche COBAS® Taqman quantitative RT-PCR assay, v2.0, which had a LLoQ of 1.2 Log IU/mL (15 IU/mL) and a LLoD below 15 IU/ml (no specific value). Undetectable HCV RNA was defined as HCV RNA target not detected. The percentage of participants with HCV RNA <LLoQ at TW2, TW4, TW12, EOT, FUWK4, FUWK12, and FUWK24 is summarized for each arm. The Clopper-Pearson method was used to construct 95% CIs for SVR rates.
Part 1 TW2, TW4, TW12, EOT, FUWK4, FUWK12, FUWK24
Part 2: Percentage of Participants Achieving Undetectable HCV RNA Over Time After Active Treatment
Lasso di tempo: Part 2: Active TW2, TW4, TW12, End of Treatment (EOT), FUWK4, FUWK12, FUWK24
Blood was drawn from each participant to assess HCV RNA plasma levels using the Roche COBAS® Taqman quantitative RT-PCR assay, v2.0, which had a LLoQ of 1.2 Log IU/mL (15 IU/mL) and a LLoD below 15 IU/ml (no specific value). Undetectable HCV RNA was defined as HCV RNA target not detected. The percentage of participants with undetectable HCV RNA at TW2, TW4, TW12, EOT, FUWK4, FUWK12, and FUWK24 is summarized for each arm. Data reported for the Part 2 Deferred Treatment Arm corresponds to the deferred active treatment weeks and subsequent follow-up. The Clopper-Pearson method was used to construct 95% CIs for SVR rates.
Part 2: Active TW2, TW4, TW12, End of Treatment (EOT), FUWK4, FUWK12, FUWK24
Part 2: Percentage of Participants Achieving HCV RNA <LLoQ Over Time After Active Treatment
Lasso di tempo: Part 2: Active TW2, TW4, TW12, End of Treatment (EOT), FUWK4, FUWK12, FUWK24
Blood was drawn from each participant to assess HCV RNA plasma levels using the Roche COBAS® Taqman quantitative RT-PCR assay, v2.0, which had a LLoQ of 1.2 Log IU/mL (15 IU/mL) and a LLoD below 15 IU/ml (no specific value). Undetectable HCV RNA was defined as HCV RNA target not detected. The percentage of participants with HCV RNA <LLoQ at TW2, TW4, TW12, EOT, FUWK4, FUWK12, and FUWK24 is summarized for each arm. Data reported for the Part 2 Deferred Treatment Arm corresponds to the deferred active treatment weeks and subsequent follow-up. The Clopper-Pearson method was used to construct 95% CIs for SVR rates.
Part 2: Active TW2, TW4, TW12, End of Treatment (EOT), FUWK4, FUWK12, FUWK24

Collaboratori e investigatori

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

Sponsor

Merck Sharp & Dohme LLC

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

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)

1 agosto 2014

Completamento primario (Effettivo)

2 ottobre 2015

Completamento dello studio (Effettivo)

16 maggio 2016

Date di iscrizione allo studio

Primo inviato

25 luglio 2014

Primo inviato che soddisfa i criteri di controllo qualità

25 luglio 2014

Primo Inserito (Stima)

29 luglio 2014

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

24 settembre 2018

Ultimo aggiornamento inviato che soddisfa i criteri QC

23 agosto 2018

Ultimo verificato

1 agosto 2018

Maggiori informazioni

Termini relativi a questo studio

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • 5172-058
  • 142638 (Identificatore di registro: JAPIC-CTI)

Piano per i dati dei singoli partecipanti (IPD)

Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?

Sì

Descrizione del piano IPD

https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

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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