Safety and Efficacy of Grazoprevir (MK-5172) + Elbasvir (MK-8742) in Participants With Chronic Hepatitis C and Chronic Kidney Disease (MK-5172-052) (C-SURFER)
23 agosto 2018 aggiornato da: Merck Sharp & Dohme LLC
A Phase II/III Randomized Clinical Trial to Study the Efficacy and Safety of the Combination Regimen of MK-5172 and MK-8742 in Subjects With Chronic Hepatitis C Virus Infection and Chronic Kidney Disease
This study will evaluate the safety and efficacy of combination treatment with grazoprevir (MK-5172) + elbasvir (MK-8742) for cirrhotic and non-cirrhotic participants with chronic Genotype 1 (GT1) hepatitis C virus (HCV) infection and chronic kidney disease (CKD).
The primary study hypothesis is that the proportion of HCV GT1-infected CKD participants within the Immediate Treatment and Intensive Pharmacokinetics (PK) groups achieving a sustained viral response 12 weeks after the end of all study treatment (SVR12) will be >45%.
Panoramica dello studio
Stato
Completato
Condizioni
Intervento / Trattamento
Tipo di studio
Interventistico
Iscrizione (Effettivo)
237
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
18 anni e precedenti (Adulto, Adulto più anziano)
Accetta volontari sani
No
Sessi ammissibili allo studio
Tutto
Descrizione
Inclusion Criteria:
- Documented chronic (at least 6 months) HCV GT 1 infection (with no evidence of mixed genotypes or genotype that cannot be assigned a type)
- Evidence or no evidence of liver cirrhosis based on one of the following:
- Liver biopsy performed within 24 months of Day 1 (if participant is cirrhotic then there is no time restriction on biopsy)
- Fibroscan performed within 12 months of Day 1 of this study
- Fibrosure™ (Fibrotest™) plus aspartate aminotransferase to platelet Ratio Index [APRI] obtained during the screening period)
- Has HCV status that is one of the following:
- Treatment naïve
- Prior interferon or pegylated interferon with or without ribavarin failures (null responder, partial responder, or relapser)
- Intolerant to prior interferon or pegylated intereferon with or without ribavarin regimen
- Chronic kidney disease (defined as glomerular filtration rate [eGFR] <=29) non-dialysis dependent or on hemodialysis for at least 3 months, including individuals awaiting kidney transplant and those with failed kidney transplants but no longer on immunosuppressant therapy)
- Female participant of reproductive potential must agree to remain abstinent or use (or have their partner use) 2 acceptable methods of contraception from at least 2 weeks prior to Day 1 through 14 days after the last dose of study drugs, or longer if dictated by local regulations
Exclusion Criteria:
- Evidence of decompensated liver disease
- On peritoneal dialysis for management of kidney disease
- Co-infection with hepatitis B virus or human immunodeficiency virus (HIV)
- History of malignancy <=5 years prior to signing informed consent
- Clinical diagnosis of substance abuse
- Pregnant, breast-feeding, expecting to conceive or donate eggs, or donate sperm from Day 1 through 14 days after the last study dose, or longer if dictated by local regulations
- Organ transplant (including hematopoietic stem cell transplant) other than kidney, cornea, and hair
- Conditions requiring, or likely to require, chronic systemic administration of corticosteroids during the course of the trial
- Uncontrolled or poorly controlled hypertension
- Significant cardiovascular disorder (e.g. myocardial infarction or unstable angina) or cardiovascular procedure within 3 months prior to signing informed consent
- New or worsening signs or symptoms of congestive heart failure within 3 months of signing informed consent
- Severe active peripheral vascular disease
- Recent (within 3 months prior to signing informed consent) episode or recurrence of stroke, transient ischemic attack (TIA) or neurological disorder, including but not limited to seizures
- Evidence or history of chronic hepatitis not caused by HCV
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: Immediate Treatment
Participants receive grazoprevir 100 mg tablet, orally, once per day (QD) + elbasvir 50 mg tablet, orally, QD, for 12 weeks.
|
Grazoprevir 100 mg tablet
Altri nomi:
Elbasvir 50 mg tablet
Altri nomi:
|
|
Sperimentale: Deferred Treatment
Participants receive placebos to both grazoprevir and elbasvir for 12 weeks, and after a 4-week break, grazoprevir 100 mg tablet, orally, QD + elbasvir 50 mg tablet, orally, QD for 12 weeks.
|
Grazoprevir 100 mg tablet
Altri nomi:
Elbasvir 50 mg tablet
Altri nomi:
Placebo tablet matched to grazoprevir
Placebo tablet matched to elbasvir
|
|
Sperimentale: Intensive PK
Participants receive grazoprevir 100 mg tablet, orally, QD + elbasvir 50 mg tablet, orally, QD for 12 weeks with intensive PK testing.
|
Grazoprevir 100 mg tablet
Altri nomi:
Elbasvir 50 mg tablet
Altri nomi:
|
Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
|
Percentage of Participants With Sustained Virologic Response 12 Weeks After Completing Study Therapy (SVR12)
Lasso di tempo: Week 24 (Immediate Treatment + Intensive PK) or Week 40 (Deferred Treatment)
|
SVR12 was defined as hepatitis C virus (HCV) ribonucleic acid (RNA) lower than the limit of quantification (LLoQ) 12 weeks after completing study therapy.
HCV RNA was measured using the COBAS™ AmpliPrep/COBAS™ Taqman™ HCV Test, v2.0®, which has a LLoQ of 15 IU/mL.
|
Week 24 (Immediate Treatment + Intensive PK) or Week 40 (Deferred Treatment)
|
|
Number of Participants Experiencing an Adverse Event (AE) During the Initial Treatment and 14-day Follow-up Periods
Lasso di tempo: Up to Week 14
|
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
This analysis includes the Immediate Treatment + Intensive PK group and the placebo treatment period for the Deferred Treatment group.
|
Up to Week 14
|
|
Number of Participants Discontinuing Study Drug Due to AEs During the Initial Treatment Period
Lasso di tempo: Up to Week 12
|
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
This analysis includes the Immediate Treatment + Intensive PK group and the placebo treatment period for the Deferred Treatment group.
|
Up to Week 12
|
Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
|
Percentage of Participants With Sustained Virologic Response 24 Weeks After Completing Study Therapy (SVR24)
Lasso di tempo: Week 36 (Immediate Treatment + Intensive PK) or Week 52 (Deferred Treatment)
|
SVR24 was defined as HCV RNA <LLoQ 24 weeks after completing study therapy.
HCV RNA was measured using the COBAS™ AmpliPrep/COBAS™ Taqman™ HCV Test, v2.0®, which has a LLoQ of 15 IU/mL.
|
Week 36 (Immediate Treatment + Intensive PK) or Week 52 (Deferred Treatment)
|
|
Percentage of Participants With Sustained Virologic Response 4 Weeks After Completing Study Therapy (SVR4)
Lasso di tempo: Week 16 (Immediate Treatment + Intensive PK) or Week 32 (Deferred Treatment)
|
SVR4 was defined as HCV RNA <LLoQ 4 weeks after completing study therapy.
HCV RNA was measured using the COBAS™ AmpliPrep/COBAS™ Taqman™ HCV Test, v2.0®, which has a LLoQ of 15 IU/mL.
|
Week 16 (Immediate Treatment + Intensive PK) or Week 32 (Deferred Treatment)
|
Collaboratori e investigatori
Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.
Sponsor
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
- Jacobson IM, Lawitz E, Kwo PY, Hezode C, Peng CY, Howe AYM, Hwang P, Wahl J, Robertson M, Barr E, Haber BA. Safety and Efficacy of Elbasvir/Grazoprevir in Patients With Hepatitis C Virus Infection and Compensated Cirrhosis: An Integrated Analysis. Gastroenterology. 2017 May;152(6):1372-1382.e2. doi: 10.1053/j.gastro.2017.01.050. Epub 2017 Feb 11.
- Reau N, Robertson MN, Feng HP, Caro L, Yeh WW, Nguyen BT, Wahl J, Barr E, Hwang P, Klopfer SO. Concomitant proton pump inhibitor use does not reduce the efficacy of elbasvir/grazoprevir: A pooled analysis of 1,322 patients with hepatitis C infection. Hepatol Commun. 2017 Aug 22;1(8):757-764. doi: 10.1002/hep4.1081. eCollection 2017 Oct.
- Roth D, Nelson DR, Bruchfeld A, Liapakis A, Silva M, Monsour H Jr, Martin P, Pol S, Londono MC, Hassanein T, Zamor PJ, Zuckerman E, Wan S, Jackson B, Nguyen BY, Robertson M, Barr E, Wahl J, Greaves W. Grazoprevir plus elbasvir in treatment-naive and treatment-experienced patients with hepatitis C virus genotype 1 infection and stage 4-5 chronic kidney disease (the C-SURFER study): a combination phase 3 study. Lancet. 2015 Oct 17;386(10003):1537-45. doi: 10.1016/S0140-6736(15)00349-9. Epub 2015 Oct 5. Erratum In: Lancet. 2015 Nov 7;386(10006):1824.
- Bruchfeld A, Roth D, Martin P, Nelson DR, Pol S, Londono MC, Monsour H Jr, Silva M, Hwang P, Arduino JM, Robertson M, Nguyen BY, Wahl J, Barr E, Greaves W. Elbasvir plus grazoprevir in patients with hepatitis C virus infection and stage 4-5 chronic kidney disease: clinical, virological, and health-related quality-of-life outcomes from a phase 3, multicentre, randomised, double-blind, placebo-controlled trial. Lancet Gastroenterol Hepatol. 2017 Aug;2(8):585-594. doi: 10.1016/S2468-1253(17)30116-4. Epub 2017 May 30.
- Caro L, Wenning L, Feng HP, Guo Z, Du L, Bhagunde P, Fandozzi C, Panebianco D, Marshall WL, Butterton JR, Iwamoto M, Yeh WW. Pharmacokinetics of elbasvir and grazoprevir in subjects with end-stage renal disease or severe renal impairment. Eur J Clin Pharmacol. 2019 May;75(5):665-675. doi: 10.1007/s00228-018-2585-3. Epub 2019 Jan 25.
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)
17 marzo 2014
Completamento primario (Effettivo)
11 marzo 2015
Completamento dello studio (Effettivo)
2 settembre 2015
Date di iscrizione allo studio
Primo inviato
17 marzo 2014
Primo inviato che soddisfa i criteri di controllo qualità
17 marzo 2014
Primo Inserito (Stima)
20 marzo 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
- Malattie dell'apparato digerente
- Infezioni da virus a RNA
- Malattie virali
- Infezioni
- Infezioni a trasmissione ematica
- Malattie trasmissibili
- Malattie urologiche
- Malattie del fegato
- Insufficienza renale
- Flaviviridae Infezioni
- Epatite, virale, umana
- Infezioni da enterovirus
- Infezioni da Picornaviridae
- Epatite cronica
- Malattie renali
- Insufficienza renale cronica
- Epatite
- Epatite A
- Epatite C
- Epatite C, cronica
- Agenti antinfettivi
- Agenti antivirali
- Grazoprevir
Altri numeri di identificazione dello studio
- 5172-052
- 2013-003858-25 (Numero EudraCT)
Piano per i dati dei singoli partecipanti (IPD)
Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?
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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 .