- ICH GCP
- US Clinical Trials Registry
- Klinisk utprøving NCT02105467
Study of Efficacy and Safety of Grazoprevir (MK-5172)/Elbasvir (MK-8742) Combination Regimen for Treatment-Naïve Participants With Chronic Hepatitis C Virus Genotypes 1, 4, and 6 (MK-5172-060)
3. september 2018 oppdatert av: Merck Sharp & Dohme LLC
A Phase III Randomized Clinical Trial to Study the Efficacy and Safety of the Combination Regimen of MK-5172/MK-8742 in Treatment-Naïve Subjects With Chronic HCV GT1, GT4, and GT6 Infection.
This was an efficacy and safety study of grazoprevir (MK-5172) in combination with elbasvir (MK-8742) in treatment-naive participants with chronic hepatitis C virus (HCV) genotype (GT) 1, 4, or 6 infection.
Participants were randomly assigned (3:1 ratio) to immediate treatment or deferred treatment (placebo control).
The primary efficacy hypothesis was that the proportion of participants receiving combination therapy in the Immediate Treatment Arm who achieve sustained viral response at 12 weeks after the end of study treatment (SVR12) is superior to 73%.
Studieoversikt
Status
Fullført
Forhold
Intervensjon / Behandling
Studietype
Intervensjonell
Registrering (Faktiske)
421
Fase
- Fase 3
Deltakelseskriterier
Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
18 år og eldre (Voksen, Eldre voksen)
Tar imot friske frivillige
Nei
Kjønn som er kvalifisert for studier
Alle
Beskrivelse
Inclusion criteria:
- Documented chronic HCV GT1, GT4, or GT6 with no evidence of non-typeable or mixed genotype infection (positive for anti-HCV antibody, HCV RNA, or any of the listed GTs at least 6 months prior to screening must be confirmed by screening lab results)
- Cirrhosis defined by: liver biopsy showing cirrhosis METAVIR F4; or Fibroscan showing cirrhosis with a result of >12.5 kiloPascals (kPa); or FibroSure® (Fibrotest®) score of >0.75 and an aspartate aminotransferase (AST): platelet ratio index (APRI) of >2
- Absence of cirrhosis defined by: liver biopsy showing absence of cirrhosis, or Fibroscan with a result of ≤12.5 kPa, or Fibrosure® (Fibrotest®) score of <= 0.48 and APRI of <=1
- HCV treatment status of treatment naïve (naïve to all anti-HCV treatment) and can also be ineligible to take pegylated interferon
- Female participant not of reproductive potential, or female of reproductive potential and agrees to avoid becoming pregnant while receiving study drug and for 14 days after the last dose of study drug (using abstinence or acceptable methods of contraception)
Exclusion criteria:
- 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. For cirrhotics, participants who are Child-Pugh Class B or C or who have a Pugh-Turcotte (CPT) score >6
- Co-infection with hepatitis B virus or human immunodeficiency virus (HIV)
- History of malignancy <=5 years prior to signing informed consent except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer or carcinoma in situ; or is under evaluation for other active or suspected malignancy
- Evidence of hepatocellular carcinoma (HCC) or under evaluation for HCC
- Currently participating or has participated in a study with an investigational compound within 30 days of signing informed consent and is not willing to refrain from participating in another such study during the course of this study
- Clinically-relevant drug or alcohol abuse within 12 months of screening
- Pregnant, breast-feeding, or expecting to conceive or donate eggs from Day 1 throughout treatment and 14 days after the last dose of study medication or longer if dictated by local regulations
- Organ transplant (including hematopoietic stem cell transplants) other than cornea and hair
- Poor venous access
- History of gastric surgery (e.g., stapling, bypass) or history of malabsorption disorder (e.g., celiac sprue disease)
- 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
- Evidence of history of chronic hepatitis not caused by HCV, including but not limited to nonalcoholic steatohepatitis (NASH), drug-induced hepatitis, and autoimmune hepatitis
Studieplan
Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Randomisert
- Intervensjonsmodell: Parallell tildeling
- Masking: Dobbelt
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
|
Eksperimentell: Immediate Treatment Group
Participants received blinded grazoprevir 100 mg / elbasvir 50 mg fixed-dose combination (FDC) tablet orally once daily for 12 weeks followed by a 24-week follow-up period
|
|
|
Placebo komparator: Deferred Treatment Group
Participants received blinded placebo tablet orally once daily for 12 weeks; after a 4-week unblinding/washout period participants received open label grazoprevir 100 mg / elbasvir 50 mg FDC tablet orally once daily for 12 weeks.
Follow-up was continued for an additional 24 weeks.
|
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Percentage of Participants Achieving Sustained Virologic Response at 12 Weeks After the End of Treatment (SVR12)
Tidsramme: Week 24 (12 weeks after the end of treatment)
|
Hepatitis C Virus (HCV) ribonucleic acid (RNA) was measured using the Roche COBAS® Taqman® HCV Test, v2.0 assay.
SVR12 was defined as HCV RNA <Lower Limit of Quantification (<15 IU/mL) 12 weeks after the end of all study therapy.
|
Week 24 (12 weeks after the end of treatment)
|
|
Percentage of Participants Experiencing at Least One Adverse Event
Tidsramme: Up to Week 14 (14 days after the Blinded Treatment was completed)
|
An adverse event is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.
An adverse event can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), 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, is also an adverse event.
|
Up to Week 14 (14 days after the Blinded Treatment was completed)
|
|
Percentage of Participants Discontinued From Study Treatment Because of an Adverse Event
Tidsramme: Up to Week 12 (end of Blinded Treatment)
|
An adverse event is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.
An adverse event can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), 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, is also an adverse event.
|
Up to Week 12 (end of Blinded Treatment)
|
Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Percentage of Participants Achieving Sustained Virologic Response at 24 Weeks After the End of Treatment (SVR24)
Tidsramme: Week 36 (24 weeks after the end of treatment)
|
Hepatitis C Virus RNA was measured using the Roche COBAS® Taqman® HCV Test, v2.0 assay.
SVR24 was defined as HCV RNA <Lower Limit of Quantitation (<15 IU/mL) 24 weeks after the end of all study therapy.
|
Week 36 (24 weeks after the end of treatment)
|
Andre resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Percentage of Participants Achieving Sustained Virologic Response at 4 Weeks After the End of Treatment (SVR4)
Tidsramme: Week 16 (4 weeks after the end of treatment)
|
Hepatitis C Virus RNA was measured using the Roche COBAS® Taqman® HCV Test, v2.0 assay.
SVR4 was defined as HCV RNA <Lower Limit of Quantitation (<15 IU/mL) 4 weeks after the end of all study therapy.
|
Week 16 (4 weeks after the end of treatment)
|
Samarbeidspartnere og etterforskere
Det er her du vil finne personer og organisasjoner som er involvert i denne studien.
Sponsor
Publikasjoner og nyttige lenker
Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.
Generelle publikasjoner
- 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.
- Zeuzem S, Ghalib R, Reddy KR, Pockros PJ, Ben Ari Z, Zhao Y, Brown DD, Wan S, DiNubile MJ, Nguyen BY, Robertson MN, Wahl J, Barr E, Butterton JR. Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial. Ann Intern Med. 2015 Jul 7;163(1):1-13. doi: 10.7326/M15-0785.
- Asselah T, Reesink H, Gerstoft J, de Ledinghen V, Pockros PJ, Robertson M, Hwang P, Asante-Appiah E, Wahl J, Nguyen BY, Barr E, Talwani R, Serfaty L. Efficacy of elbasvir and grazoprevir in participants with hepatitis C virus genotype 4 infection: A pooled analysis. Liver Int. 2018 Sep;38(9):1583-1591. doi: 10.1111/liv.13727. Epub 2018 Mar 31.
- 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.
Studierekorddatoer
Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.
Studer hoveddatoer
Studiestart (Faktiske)
5. juni 2014
Primær fullføring (Faktiske)
26. februar 2015
Studiet fullført (Faktiske)
6. september 2015
Datoer for studieregistrering
Først innsendt
2. april 2014
Først innsendt som oppfylte QC-kriteriene
2. april 2014
Først lagt ut (Anslag)
7. april 2014
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
2. oktober 2018
Siste oppdatering sendt inn som oppfylte QC-kriteriene
3. september 2018
Sist bekreftet
1. september 2018
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
- Sykdommer i fordøyelsessystemet
- RNA-virusinfeksjoner
- Virussykdommer
- Infeksjoner
- Blodbårne infeksjoner
- Smittsomme sykdommer
- Leversykdommer
- Flaviviridae-infeksjoner
- Hepatitt, viral, menneskelig
- Enterovirusinfeksjoner
- Picornaviridae-infeksjoner
- Hepatitt
- Hepatitt A-virus
- Hepatitt C
- Hepatitt, kronisk
- Hepatitt C, kronisk
- Anti-infeksjonsmidler
- Antivirale midler
- Grazoprevir
- Elbasvir-grazoprevir medikamentkombinasjon
Andre studie-ID-numre
- 5172-060
- 2014-000137-22 (EudraCT-nummer)
Plan for individuelle deltakerdata (IPD)
Planlegger du å dele individuelle deltakerdata (IPD)?
JA
IPD-planbeskrivelse
https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .