A Phase III Open-LabelRandomized Clinical Trial to Study the Efficacy and Safety of the Combination Regimen of MK-5172/MK-8742 in Treatment-Naive Subjects with Chronic HCV GT1, GT4, GT5, and GT6 Infection who are on Opiate Substitution Therapy.

Study ID
STU 042014-029

Cancer Related
No

Healthy Volunteers
No

Study Sites

  • Clements University Hospital
  • UT Southwestern Ambulatory Services
  • UT Southwestern-Other

Contact
Nahid Attar
214/645-6188
NAHID.ATTAR@UTSouthwestern.edu

Principal Investigator
William Lee, M.D.

Summary

abbreviated Title: MK-5172 in Combination with MK-8742 in Subjects on opiate
Substitution Therapy.
Trial Phase: Phase iii
Clinical indication: Treatment of hepatitis C virus infection
Trial: Type interventional
Type of control: Placebo
Route of administration: oral
Trial Blinding unblinded: Double-Blind
Treatment Groups: immediate Blinded Treatment:
arm 1: MK-5172a 100mg/50mg (100 mg MK-5172 100 mg +/50mg
MK-8742 50 mg) for 12 weeks
Deferred Treatment Blinded for first 12 weeks Followed by 12
Weeks of open-Label Therapy:
arm 2: Placebo for 12 weeks followed by open-label treatment for 12
weeks MK-5172 100 mg + MK-8742 50 mg for 12 Weeks
number of trial subjects: approximately 300 subjects will be enrolled.
estimated duration of trial: each subject will participate in the trial for approximately 42.5 or 58.5
weeks (maximum depending on the treatment arm) from the time the
subject signs the informed Consent Form (iCF) through the final
contact. after a screening phase of 45 days or (6.5 weeks,) each
subject will be receiving assigned treatment for approximately 12 or
24 weeks. after the end of treatment each subject will be followed for
24 weeks for a total of up to 42.5(deferred treatment arm will be
followed for an additional 4 weeks in the study.
post-placebo treatment).

Participant Eligibility

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. HCV RNA (>= 10,000 IU/mL in peripheral blood) confirmed by screening lab results
3. have documented chronic HCV GT1, GT4, and GT6 infection (with no evidence of
GT2 or GT3 or non typeable genotypes. Mixed genotypes are allowed but not if they
include GT2 or GT3 confirmed by screening lab results

* Positive for anti-HCV antibody, HCV RNA, or any of the above HCV genotypes
at least 6 months before screening or

* Positive for anti-HCV antibody 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 on opiate substitution therapy (OST) for at least 3 months prior to screening.
Medications recognized as components of opiate substitution therapy include:
methadone, levamethadone, buprenorphine, naloxone, and naltrexone.
5. must have consistently kept at least 80% of scheduled appointments while on OST.
6. must have not missed any scheduled appointments between screening and study entry
(Day 1

7. have liver disease staging assessment as follows:
Cirrhosis is defined as any one of the following:[44,45]

* a liver biopsy performed prior to Day 1 of this study showing cirrhosis (F4).

* Fibroscan performed within 12 calendar months of Day 1 of this study showing
cirrhosis with result >12.5 kPa* [45].

* a FibroSure(RegisteredTM) (Fibrotest(RegisteredTM)) performed during Screening with a score of >0.75 and an
aspartate aminotransferase (AST):platelet ratio index (APRI) of >2. APRI formula:
AST[?]lab upper limit of normal (ULN) for AST x 100[?]{platelet count[?]100} (APRI
calculation to be provided by the central laboratory).
Absence of cirrhosis is defined as any one of the following:

* liver biopsy performed within 24 months of Day 1 of this study showing absence of
cirrhosis.

* Fibroscan performed within 12 months of Day 1 of this study with a result of <=12.5
kPa*[45].

* a FibroSure(RegisteredTM) (Fibrotest(RegisteredTM)) score of <=0.48 and Aspartate Aminotransferase to Platelet
Ratio Index (APRI) of <=1 during Screening.
*Fibroscan cut-off of 12.5 kPa has a positive predictive value of 90% and a sensitivity of 95% for
>=F3. Based on box and whisker plot of interquartile distribution >12.5 kPa will exclude the majority of
subjects with metavir F3 fibrosis.
In the absence of a definitive diagnosis of presence or absence of cirrhosis by the above
critieria, a liver biopsy is required. Liver biopsy results supersede the results obtained by
Fibroscan or FibroSure(RegisteredTM).
8. Be HCV treatment naive: Naive to all anti-HCV treatment
Note: Includes subjects who are treatment naive who are ineligible to take IFN. See
Section 7.1.2.1 for more details and definitions.
9. HIV-1 infected, subjects enrolled in this study must meet the following criteria:;
a. Have HIV infection documented by any licensed rapid HIV test or HIV
enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior
to study entry (Day 1) and confirmed by a licensed Western blot or a second
antibody test by a method other than the initial rapid HIV and/or E/CIA, or by
HIV-1 p24 antigen, or plasma HIV-1 RNA viral load.
b. be naive to treatment with any antiretroviral therapy (ART) (and have no
plans to initiate ART treatment while participating in this study and through at
least Follow-up Week 4 OR be on HIV Antiretroviral Therapy (ART) for at
least 8 weeks prior to study entry using a dual NRTI backbone of tenofovir or
abacavir and either emtricitabine or lamivudine PLUS raltegravir [or
dolutegravir or rilpivirine]. Note: Dose modifications or changes in ART
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during the 4 weeks prior to study entry (Day 1) are not permitted. Subjects on
ART should plan to remain on the same therapy through at least Follow-up
Week 4 of this study.
c. have CD4+ T-cell count > 200 cells/mm3 at screening (for subjects currently
on stable ART); CD4+ T-cell count > 500 cells/mm3 at screening (for subjects
who are naive to treatment with ART).
d. have HIV-1 RNA TND at screening and at least 8 weeks prior to screening if
on ART and HIV RNA <50,000 copies/mL if not on ART.
e. for subjects with HIV-1 infection and on ART, have at least one viable
antiretroviral regimen alternative beyond their current regimen in the event of
HIV virologic failure or the development of anti-retroviral drug resistance
10. agree to the following:

* The subject is a female who is not of reproductive potential, defined as a female who
either: (1) is postmenopausal (defined as at least 12 months with no menses in women
>=45 years of age); (2) has had a hysterectomy and/or bilateral oophorectomy, bilateral
salpingectomy, or bilateral tubal ligation/occlusion at least 6 weeks prior to screening;
OR (3) has a congenital or acquired condition that prevents childbearing.

* The subject is a female who is of reproductive potential and agrees to avoid becoming
pregnant while receiving study drug and for 14 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 her partner use) acceptable contraception during
heterosexual activity. Acceptable methods of contraception are[?]:
Single method (one of the following is acceptable):

* intrauterine device (IUD)

* vasectomy of a female subject[Single Quote]s male partner

* contraceptive rod implanted into the skin
Combination method (requires use of two of the following):

* diaphragm with spermicide (cannot be used in conjunction with cervical
cap/spermicide)

* cervical cap with spermicide (nulliparous women only)
[?] Abstinence (relative to heterosexual activity) can be used as the sole method of contraception if it is consistently employed as the subject[Single Quote]s preferred and usual lifestyle and if considered acceptable by local regulatory agencies and ERCs/IRBs. Periodic abstinence (e.g., calendar, ovulation, sympto-thermal, postovulation methods, etc.) and withdrawal are not acceptable methods of contraception.
[?] If a contraceptive method listed above is restricted by local regulations/guidelines, then it does not qualify as
an acceptable method of contraception for subjects participating at sites in this country/region.
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* contraceptive sponge (nulliparous women only)

* male condom or female condom (cannot be used together)

* hormonal contraceptive: oral contraceptive pill (estrogen/progestin pill or progestinonly
pill), contraceptive skin patch, vaginal contraceptive ring, or subcutaneous
contraceptive injection
11. understand the study procedures, alternative treatments available, risks involved with the
study, and voluntarily agrees to participate by giving written informed consent.
12. provide written informed consent for the trial .The subject may also provide consent for
Future Biomedical Research. However, the subject may participate in the main trial
without participating in Future Biomedical Research.