A Phase II/III Randomized Clinical Trial to Study the Efficacy and Safety of the Combination Regimen of MK-5172 and MK-8742 in Subjects with Chronic Hepatitis C Virus Infection and Chronic Kidney Disease

Phase 2

Completed

• Conditions: Chronic Hepatitis C and Chronic Renal Insufficiency; Liver inflammation and Kidney Disease; 10047438; 10038430

• Registration Number: NL-OMON40914
• Lead Sponsor: Merck Sharp & Dohme (MSD)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 23 April 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 6

Inclusion Criteria

1. Be >=18 years of age on day of signing informed consent.
2. Have documented chronic (at least 6 months) HCV GT1 infection (with no evidence of non typable or mixed genotypes) :
• Positive for anti-HCV antibody, HCV RNA, or an HCV genotype
• HCV RNA (>= 10,000 IU/mL in peripheral blood)
3.Subjects with or without cirrhosis may be enrolled into this study. All subjects must have one of the below liver disease staging assessments as follows:
• Liver biopsy performed within 24 months of Day 1 (if subject is cirrhotic then there is no time restriction on biopsy)
• Fibroscan performed within 12 months of Day 1
• A FibroSure® (Fibrotest®) and Aspartate Aminotransferase to Platelet
Ratio Index (APRI) (APRI is automatically calculated by central laboratory) during Screening
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®.
4. Have an HCV treatment status that is one of the following:
Treatment naïve: Naive to all anti-HCV treatment
Prior IFN or PEG-IFN + Ribavirin Treatment failures: Null responders, Partial responders, Relapsers. P/R Intolerant: Subjects were intolerant to a prior IFN or PEG-IFN ± Ribavirin regimen, Subjects discontinued treatment prematurely and were therefore unable to complete a full course of therapy because of drug-related toxicity.
5. Have Chronic Kidney Disease defined as:
Subjects with GFR <=29 who are non-dialysis dependent (NDD) or have been on
hemodialysis (HD) for at least 3 months (including subjects awaiting kidney transplant
and subjects with failed kidney transplants no longer on immunosuppressant therapy).
6. Agree (if subject is of reproductive potential) to remain truly abstinent or use (or have
their partner use) 2 acceptable methods of birth control from at least 2 weeks prior to Day
1 and through 14 days after the last dose of study drugs, or longer if dictated by local regulations.
If acceptable by local regulatory agencies, methods of birth control allowed in the study
are: intrauterine device (IUD), diaphragm with spermicide, hormonal contraceptives (e.g.,
birth control pills, transdermal patch, or injectables), contraceptive sponge, female
condom, male condom with spermicide or vasectomy.
7. A female subject who is not of reproductive potential is eligible without requiring the use
of contraception. A female subjects who is not of reproductive potentials is defined as
one who has either 1) reached natural menopause (defined as 12 months with no menses
without an alternative medical cause), 2) 6 weeks post surgical bilateral oophorectomy
with or without hysterectomy, or 3) bilateral tubal ligation.
8. A male subject who is not of reproductive potential is eligible without requiring the use of
contraception. A male subject who is not of reproductive potential is defined as: one who
has undergone a successful vasectomy. A successful vasectomy is defined as: (1)
microscopic documentation of azoospermia, or (2) a vasectomy more than 2 years ago
with no resultant pregnancy despite sexual activity post vasectomy.
9. understand the study procedures, alternative treatments available, risks involved with the
study, and voluntarily agrees to participate by giving written informed consent.
10. The subje

Exclusion Criteria

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. Evidence of decompensated liver disease manifested by the presence of or history of ascites, gastric or variceal bleeding, hepatic encephalopathy or other signs or symptoms of advanced liver disease.
3. Is on peritoneal dialysis for management of Kidney disease
4. In the opinion of the investigator the subject has a high likelihood of receiv ing a renal transplant during the study treatment period (up to 24 weeks from Day 1).
5. Is coinfected with hepatitis B virus (e.g. HBsAg positive) or HIV.
6. 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 has evidence of hepatocellular carcinoma (HCC) or is under evaluation for other active or suspected malignancy.
7. Is taking or plans to take any of the prohibited medications listed in Section 5 of this protocol within 2 weeks of Day 1.
8. 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.
9. has a clinical diagnosis of substance abuse of the following specified drugs within specified timeframes:
• 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, if shorter is judged by the investigator to be capable of complying with study procedures, OR
• history of 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.
10. Female subject who is pregnant or breast-feeding, or expecting to conceive or donate eggs from Day 1 and through 14 days after the last dose of study drugs, or longer if dictated by local regulations or male subject who is expecting to donate sperm from Day 1 and through 14 days after the last dose of study drugs, or longer if dictated by local regulations.
11. Has any of the following conditions:
• Organ transplants (including hematopoietic stem cell transplants) other than kidney, cornea and hair.
• Poor venous access in non-dialysis patients that precludes routine peripheral blood sampling required for this trial.
• Subject with a history of gastric surgery (e.g., stapling, bypass) or subject with a history of malabsorption disorders (e.g., celiac sprue disease).
• Any medical condition requiring, or likely to require, chronic systemic administration of corticosteroids during the course of the trial.
• Has uncontrolled or poorly controlled hypertension including but not limited to hypertensive emergency or hospitalization for hypertension in preceding 3 months.
• Diagnosed with a significant cardiovascular disorder (e.g. MI or unstab

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Primary Objective(s) & Hypothesis(es)<br /><br><br /><br>In subjects who have chronic kidney disease (CKD Stages 4-5) and chronic HCV<br /><br>GT1 infection with pre-treatment HCV RNA of at least 10,000 IU/mL:<br /><br><br /><br>The Primary Objective(s) are:<br /><br><br /><br>(1) Objective: To evaluate the efficacy of MK-5172 + MK-8742 in HCV GT1<br /><br>subjects with chronic kidney disease (CKD) within the immediate treatment and<br /><br>the intensive PK groups.<br /><br><br /><br>Hypothesis: The proportion of HCV GT1 infected CKD 4-5 subjects achieving SVR<br /><br>(defined as HCV RNA <LLoQ (either TD(u) or TND) 12 weeks after the end of all<br /><br>study therapy will be superior to 45% (see Section 4.2.1- Rationale for Study).<br /><br><br /><br>(2) Objective: To evaluate the safety and tolerability of MK -5172 in<br /><br>combination with MK-8742 in the immediate treatment group relative to the<br /><br>placebo treatment of the deferred treatment group.</p><br>