MK-5172/MK-3682 with MK-8742 or MK-8408 in HCV GT1, GT2, and GT4 Infected Subjects

Phase 1

• Conditions: Chronic Hepatitis C infected patient; MedDRA version: 18.1 Level: LLT Classification code 10047457 Term: Viral hepatitis C System Organ Class: 100000004862; Therapeutic area: Diseases [C] - Virus Diseases [C02]

• Registration Number: EUCTR2014-003304-73-IT
• Lead Sponsor: MERCK SHARP & DOHME CORP. UNA SUSSIDIARIA DI MERCK & CO. INC.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2016-03-10
• Study Completion: 2016-12-12
• Last Update Posted: 30 June 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 442

Inclusion Criteria

For Parts A and B:
1. be =18 years
2. HCV RNA (= 10,000 IU/mL in peripheral blood)
3. have documented chronic HCV GT1, 2, or 4 (GT4 infected subjects are only eligible for enrollment in Part B) (with no evidence of non-typeable or mixed genotype) infection:
• anti-HCV Ab +, HCV RNA+, or + to any of the above HCV GT at least 6 mo before screening, or
• anti-HCV Ab+ or HCV RNA+ at the time of screening with a liver biopsy consistent with chronic HCV infection (or a liver biopsy performed before enrollment with evidence of CHC disease, such as the presence of fibrosis)
4. Be otherwise healthy as determined by the medical history, physical examination, ECG, and clinical lab measurements performed at the time of screening
5. have liver disease staging assessment as follows:
Absence of cirrhosis is defined as any one of the following (Part A and Part B):
• Liver biopsy performed within 24 mo of Day 1 showing absence of cirrhosis
• Fibroscan performed within 12 mo of Day 1 with a result of =12.5 kPa
• A Fibrosure® (Fibrotest®) score of =0.48 and APRI =1 during Screening
Compensated cirrhosis is defined as any one of the following (Part B only):
• A liver biopsy performed prior to Day 1 showing cirrhosis (F4)
• Fibroscan performed within 12 calendar mo of Day 1 with a result >12.5 kPa
• A FibroSure® (Fibrotest®) performed during Screening with a score of >0.75 and an APRI >2.
6. be HCV treatment naïve (both Part A and Part B)
7. meet one of the following:- not of reproductive potential - of reproductive potential and agrees to avoid becoming pregnant or impregnating a partner beginning at least 2 weeks prior the initial dose and for 90 days after the last dose of study drug by complying with one of the following: (1) practice abstinence† from heterosexual activity OR (2) use (or have their partner use) two forms of acceptable barrier contraception during heterosexual activity.
8. understand the study procedures, alternative treatments available, risks involved with the study, and voluntarily agrees to participate by giving written informed consent.
9. provide written informed consent for the trial. The subject may also provide consent for FBR. However, the subject may participate in the main trial without participating in FBR.
For Part B only:
For HIV co-infected subjects these criteria must also be met.
10. have HIV-1 infection documented by any licensed rapid HIV test or HIV E/CIA test kit at any time prior to Day 1 and confirmed by a licensed Western blot or a second Ab test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 p24 Ag, or plasma HIV-1 RNA viral load.
11. meet one of the following:
1. not currently and have no plans to initiate ART while in this study.
• subjects not on ART must have CD4+ T-cell count >500 cells/mm3 at screening
2. have well controlled HIV on ART, defined as:
• have achieved virologic suppression (defined as confirmed HIV RNA level below the LLOQ of available assay) on HIV ART at least 8 weeks prior to Day 1.
1. The ART regimen must con

Exclusion Criteria

The following applies to Parts A, B and C:
1. is under the age of legal consent, is mentally or legally incapacitated, has significant emotional problems at the time of pre-study screening visit or expected during the conduct of the study or has a history of a clinically significant psychiatric disorder which would interfere with the study procedures.
2.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.
3.For cirrhotics (Parts B and C only):
a.subjects that are Child-Pugh Class B or C or who have a Pugh-Turcotte(CPT) score > 5, must be excluded.
4.coinfected with hepatitis B virus.
5.coinfected with HIV (Part A only).
6.For subjects with HIV, has a history of opportunistic infection in the preceding 6 months prior to screening.
7.has a 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.
8.has cirrhosis and liver imaging within 6 months of Day 1 showing evidence of hepatocellular carcinoma (HCC) or is under evaluation for HCC.
9.is taking or plans to take any of the prohibited medications listed in the protocol or is taking herbal supplements within 2 weeks of Day 1.
10.For Parts A and B only: is 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.
11.has clinically-relevant drug or alcohol abuse within 12 months of screening.
12.is a female and is pregnant or breast-feeding, or expecting to conceive or donate eggs from at least 2 weeks prior to Day 1 and 90days after the last dose of study medication, or longer if dictated by local regulations. OR male subject who is expecting to donate sperm from at least 2 weeks prior to day 1 until 90 days after the last dose of study medication, or longer if dictated by local regulations.
13.has any of the following conditions:
a.Organ transplants (including hematopoietic stem cell transplants)other than cornea and hair.
b.Poor venous access that precludes routine peripheral blood sampling required for this trial.
c.subject with a history of gastric surgery or subject with a history of malabsorption disorders.
d.Current or history of any clinically significant cardiac abnormalities/dysfunction, including but not limited to: angina,congestive heart failure, myocardial infarction, pulmonary hypertension, complex congenital heart disease,cardiomyopathy, significant arrhythmia, uncontrolled hypertension, a history of use of antianginal agents for cardiac conditions, prolonged ECG QTc interval (> 470 ms for males or > 480 ms for females by either the Bazett or Fridericia formula) at the screening visit, personal or family history of Torsade de pointes.
e.Chronic pulmonary disease, including but not limited to: clinical chronic obstructive pulmonary disease, i

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified