A Clinical Trial to Test Different Doses of MK-5172 administered with Other Hepatitis C Virus Treatments

• Register: EUCTR
• Last refreshed on: 26 March 2024
• Main ID: EUCTR2012-003333-42-SE
• Date of registration: 17/10/2012
• Prospective Registration: Yes
• Primary sponsor: Merck Sharp & Dohme Corp.
• Public title: A Clinical Trial to Test Different Doses of MK-5172 administered with Other Hepatitis C Virus Treatments
• Scientific title: A Phase II Randomized, Dose Ranging, Clinical Trial to Evaluate the Safety, Tolerability, and Efficacy of Different Doses of MK-5172 When Administered Concomitantly with Peginterferon alfa-2b and Ribavirin in Treatment Naïve Subjects with Chronic Hepatitis C Virus Infection - MK-5172 + PegRiba in GT1 TN Patients Pilot Study
• Date of first enrolment: 21/12/2012
• Target sample size: 90
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-003333-42
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: yes Other specify the comparator: Comparing 3 different dose levels (25mg, 50mg, and 100mg) Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Canada, Sweden, United Kingdom, United States

Contacts

• Name: Global Clinical Trials Operations
• Affiliation: Merck Sharp & Dohme, Corp.

• Name: Global Clinical Trials Operations
• Affiliation: Merck Sharp & Dohme, Corp.

Key inclusion & exclusion criteria

Inclusion criteria:
In order to be eligible for participation in this trial, the subject must:
1. be =18 years of age on day of signing informed consent.

2. have a body weight >50 kg (111 lbs) and = 125 kg (275 lbs).

3. have chronic, compensated HCV GT 1a infection for Part A and GT1 (1a or 1b) for Part B as defined by:
• Positive serology for HCV with HCV RNA levels = 10,000 IU/mL in peripheral blood at screening, and
• Absence (no medical history or physical findings) of ascites, bleeding esophageal varices, hepatic encephalopathy, or other signs or symptoms of advanced liver disease, or cirrhosis

4. have had no evidence of cirrhosis and/or hepatocellular carcinoma. This can be confirmed either by liver biopsy or by non-invasive methods such as fibrotest or fibroscan in countries where biopsy is not the standard method of diagnosis.
• agree to use two acceptable methods of birth control from at least 2 weeks prior to Day 1 and continue until at least 6 months after last dose of study drug, or longer if dictated by local regulations (for female subject who is of childbearing potential or male subject with female sexual partner who is of childbearing potential)
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 90
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 90

Exclusion criteria:
1) has a non-GT 1 HCV infection, including a mixed GT infection (with a non-GT 1) or a non-typeable genotype.

2) is NOT treatment naïve, i.e. subject has had previous treatment with any interferon, ribavirin, approved or experimental direct acting antiviral(s), or other investigational therapies for HCV.

3) As determined by documented records, subject is HIV positive or known to be coinfected with hepatitis B virus (HBsAg positive).

4) has evidence of hepatocellular carcinoma (HCC) or is under evaluation for HCC.

5) has pre-existing psychiatric condition(s)

6) has any known medical condition that could interfere with the subject’s participation in and completion of the trial

7) has evidence of active or suspected malignancy, or a history of malignancy, within the last 5 years

8) (female) is pregnant, lactating, expecting to conceive or donate eggs, or is of childbearing potential and unwilling to commit to two methods of birth control throughout treatment and after the completion of all treatment

9) is a male whose female partner(s) are pregnant

10) has exclusionary laboratory values as listed in the protocol
i) Hemoglobin <12 g/dL for females and <13 g/dL for males.
ii) Neutrophils <1.5 x 103/µL (<1.2 x 103/µL for Blacks).
iii) Platelets <150 x 103/µL
iv) Direct bilirubin >1.5 x ULN (upper limit of normal) of the laboratory reference range
v) PT/PTT values > 10% above laboratory reference range
vi) Anti-nuclear antibodies (ANA) > 1:320
vii) ALT > 350IU/L
viii) AST > 350 IU/L
viiii) Creatinine clearance < 50 mL/min.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Chronic Hepatitis C Virus Infection
MedDRA version: 14.1 Level: PT Classification code 10019744 Term: Hepatitis C System Organ Class: 10021881 - Infections and infestations

Therapeutic area: Diseases [C] - Virus Diseases [C02]

Intervention(s)

Product Code: MK-5172
Pharmaceutical Form: Tablet
Other descriptive name: MK-5172
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Product Code: MK-5172
Pharmaceutical Form: Tablet
Other descriptive name: MK-5172
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Product Code: MK-5172
Pharmaceutical Form: Tablet
Other descriptive name: MK-5172
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Trade Name: Rebetol
Product Name: Rebetol
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Ribavirin
CAS Number: 36791-04-5
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: 800-1400

Trade Name: PegIntron
Product Name: PegIntron
Pharmaceutical Form: Powder and solution for solution for injection
CAS Number: 215647-85-1
Other descriptive name: PEGINTERFERON ALFA-2B
Concentration unit: µg microgram(s)
Concentration type: range
Concentration number: 50-150

Trade Name: PegIntron
Product Name: PegIntron
Pharmaceutical Form: Powder and solution for solution for injection
INN or Proposed INN: PEGINTERFERON ALFA-2B
CAS Number: 215647-85-1
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 50-150

Trade Name: Victrelis
Product Name: Victrelis
Product Code: MK-3034 / SCH503034
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Boceprevir
CAS Number: 394730-60-0
Concentration unit: mg milligram(s)
Concentration type: equal
Co

Primary Outcome(s)

Main Objective: (1) To evaluate the efficacy of each treatment arm of MK-5172 in combination with peg-IFN and RBV as assessed by the proportion of subjects achieving SVR12 (Sustained Virologic Response 12 weeks after the end of all study therapy).

(2) To evaluate the relative safety and tolerability of the selected doses of MK-5172 in combination with peg-IFN and RBV.

Timepoint(s) of evaluation of this end point: The endpoint will be evaluated at SVR12 (Sustained Virologic Response 12 weeks after the end of all study therapy)

Primary end point(s): The primary efficacy endpoint will be the proportion of subjects achieving SVR12

Secondary Objective: (1)Evaluate efficacy of each treatment arm of MK5172 in combination w/Peg-IFN alfa-2b and RBV,as assessed by the time to 1st achievement of undetectable HCV RNA

(2)Evaluate efficacy of each treatment arm of MK5172 in combination w/Peg-IFN alfa-2b and RBV as assessed by the proportion of subjects achieving undetectable HCV RNA and by the proportion of subjects achieving HCV RNA <25 IU/mL) at Wk 2, Wk 4, Wk 12 and end of treatment visits.

(3)Evaluate efficacy of each treatment arm of MK-5172 in combination w/Peg-IFN alfa-2b and RBV as assessed by the proportion of subjects achieving: a)SVR4(Sustained Virologic Response 4 wks after the end of all study therapy) b)SVR24 (Sustained Virologic Response 24 wks after the end of all study therapy)

(4)Evaluate emergence of antiviral resistance to MK-5172 when administered as part of combination regimen with peg-IFN and RBV

(5)Evaluate proportion of patients who receive 24 wks of therapy based on RGT

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 1. the time to first achievement of undetectable (TND) HCV RNA;

2. at Week 2, Week 4, and Week 12 and End of Treatment visits.

3. SVR4 (Sustained Virologic Response 4 weeks after the end of all study therapy)and SVR24 SVR12 (Sustained Virologic Response 24 weeks after the end of all study therapy).

4. Day 1, Day 3, Day 5, Day 7, Week 2, Week 4, Week 6, Week 8, Week 10, Week 12, Week 16, Week 20, Week 24, Viral Failure Confirmation Visit, Unscheduled/Early Discontinuation visit, Follow Up 4 Weeks after End of Treatment, Follow Up 12 Weeks after End of Treatment, and Follow Up 24 Weeks after End of Treatment.

Secondary end point(s): 1. the time to first achievement of undetectable (TND) HCV RNA

2. the proportion of subjects achieving undetectable (TND) HCV RNA and by the proportion of subjects achieving HCV RNA < 25 IU/mL at Week 2, Week 4, and Week 12 and End of Treatment visits.

3. the proportion of subjects achieving SVR4 and SVR24.

4. the emergence of antiviral resistance to MK-5172 when administered as part of a combination regimen with RBV

Secondary ID(s)

5172-038

Source(s) of Monetary Support

Merck Sharp & Dohme, Corp.

Ethics review

Status: Approved
Approval date: 21/12/2012
Contact:

Results

• Results available: Yes
• Date Posted: 25/02/2015
• Date Completed: 29/01/2014
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2012-003333-42/results