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 - Protocol 038: MK5172 with Peg-IFN & RBV in naive HCV GT1 patients

• Register: EUCTR
• Last refreshed on: 28 February 2019
• Main ID: EUCTR2012-003333-42-GB
• Date of registration: 27/12/2012
• Prospective Registration: Yes
• Primary sponsor: Merck Sharp & Dohme Corp.
• Public 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 - Protocol 038: MK5172 with Peg-IFN & RBV in naive HCV GT1 patients
• 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 - Protocol 038: MK5172 with Peg-IFN & RBV in naive HCV GT1 patients
• Date of first enrolment: 28/12/2012
• 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: yes 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 1 infection 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 a liver biopsy without evidence of cirrhosis and hepatocellular carcinoma. A liver biopsy done prior to screening is acceptable if it is performed:
• Within 3 years of screening and the result was METAVIR (or equivalent) Stage 0 (F0) to 2 (F2).
• Within 1 year of screening and the result was Stage 3 (F3).
If the prior liver biopsy was obtained outside the acceptable windows, a repeat biopsy may be performed, and the results must show no evidence of cirrhosis and hepatocellular carcinoma in order for the subject to be randomized in the study.
For countries where liver biopsy is not performed prior to treatment and where noninvasive tests (for e.g. FibroScan and/or FibroTest) are used for staging of liver disease, these results may be used to assess eligibility. Subjects with a documented FibroScan score of =9.5 kPa, or FibroTest score of =0.58, are allowed to be enrolled in the study. These non-invasive tests done prior to screening are acceptable if they were performed within 1 year of screening and meet the indicated cut-offs.

5. 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).

6. understand the study procedures, alternative treatments available, and risks involved with the study, and voluntarily agrees to participate by giving written informed consent.

7. provide written informed consent/assent for the trial. The subject may also provide consent/assent for Future Biomedical Research. However, the subject may participate in the main trial without participating in Future Biomedical Research.

Are the trial subjects under 18? no
Number of subjects for this age range: 0
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:
The subject must be excluded from participating in the trial if the subject:
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, in the opinion of the investigator, would interfere with the study procedures.

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

3. 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.

4. as determined by documented records, subject is HIV positive or known to be co-infected with hepatitis B virus (HBsAg positive).

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

6. is taking or plans to take any of the following medications:
6.1. Significant inducers or inhibitors of CYP3A4 2 weeks prior to start of study medications (see Prohibited Medications, Section 5.5 for further guidance).
6.2. Herbal supplements, including but not limited to St. John’s Wort (Hypericum perforatum) 2 weeks prior to start of study medications (Day 1). Only silymarin (Milk Thistle, Silybum marianum) is permitted during the trial.

7. is currently participating or has participated in a study with an investigational compound or device within 30 days of signing informed consent and is not willing to refrain from participating in another study. Collection of additional blood, urine, or tissue samples or additional data, beyond that specified in this protocol, is prohibited (other than that related to subject’s medical care).

8. is diabetic and/or hypertensive with clinically significant ocular examination findings: retinopathy, cotton wool spots, optic nerve disorder, retinal hemorrhage, or any other clinically significant abnormality

9. has pre-existing psychiatric condition(s)

10. has a clinical diagnosis of substance abuse of the following specified drugs within specified timeframes:
10.1. Alcohol, intravenous drugs, inhalational (not including marijuana), psychotropics, narcotics, cocaine use, prescription or over-the-counter drugs: within 1 year of the screening visit OR
10.2. Multi-drug abuse (e.g., two or more of the substances listed in Exclusion Criterion 10.1): within 1 years of screening visit OR
10.3. receiving opiate agonist substitution therapy within 1 year of screening visit.
10.4. historic marijuana use is deemed excessive by a physician investigator or is interfering with the subject's daily function. If subject's marijuana use is not deemed excessive and does not interfere with daily function, subject must be instructed to discontinue any current use of recreational marijuana prior to entry into trial and throughout the trial period.

11. has any known medical condition that could interfere with the subject’s participation in and completion of the trial, (see protocol pages 27 and 28).

12. has evidence of active or suspected malignancy, or a history of malignancy, within the

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

Health Condition(s) or Problem(s) studied

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

Chronic Hepatitis C Virus Infection

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: equal
Concentration number: 800-1400

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

Trade Name: PegIntron
Product Name: PegIntron
Pharmaceutical Form:

Primary Outcome(s)

Primary end point(s): Primary Efficacy Outcome Measure:
Sustained Virologic Response 12 weeks after the end of all study therapy.

Safety Outcome Measure:
Clinical evaluation of adverse experiences and inspection of other study parameters including vital signs, physical examinations, 12-lead ECGs, and laboratory safety tests.

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)

Main Objective: In treatment naïve subjects with chronic hepatitis C virus genotype 1 infection with pre-treatment HCV RNA of at least, 10,000IU/ml:

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 sustained virologic response 12 weeks after the end of all study therapy (SVR12).

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

Secondary Objective: In treatment naïve subjects with chronic hepatitis C virus genotype 1 infection with pre-treatment HCV RNA of at least, 10,000IU/ml:

1) To evaluate the efficacy of each treatment arm of MK-5172 in combination with peg-IFN and RBV as assessed by the time to first achievement of undetectable (THD) HCV RNA.

2) 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 undetectable (TND) HCV RNA (and HCV RNA ,25 IU/ml) as Week 2, Week 4, Week 12 and end of treatment visit.

3) 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:
-Sustained Virologic Response 4 weeks after the end of all study therapy (SV4)
-Sustained Virologic Response 24 weeks after the end of all study therapy (SV24)

4) To evaluate the emergence of antiviral resistance of MK5172 when administered as part of a combination regimen w

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)

MK5172-038

2012-003333-42-SE

Source(s) of Monetary Support

Merck Sharp & Dohme, Corp.

Ethics review

Status: Approved
Approval date:
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