A Study of the Efficacy and Safety of PPI-668 (NS5A Inhibitor) Plus Sofosbuvir, With or Without Ribavirin, in Patients With Chronic Hepatitis C Genotype-4

NCT02371408 | Unknown Phase 2

• 1 other identifier: PPI-668-202
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 3

Brief Summary

The study will assess the efficacy of PPI-668 (USAN: ravidasvir hydrochloride) in combination with sofosbuvir, with or without ribavirin, in the following Egyptian HCV gt-4 patient populations:

1. 1.Treatment-naïve patients, with and without cirrhosis (Group 1)
2. 2.Previous non-responders to interferon-based therapies, without cirrhosis (Group 2)
3. 3.Previous non-responders to interferon-based therapies, with cirrhosis (Group 3)

Conditions

Chronic Hepatitis C

Outcome Measures

Primary Outcomes (1)

• Proportions of patients who achieve Sustained Virologic Response at 12 weeks post-treatment (SVR12)

  Sustained Virologic Response is defined as serum HCV RNA \< LLOQ at post-treatment visits.

  post-treatment week 12

Secondary Outcomes (4)

• Proportions of patients who achieve Sustained Virologic Response at 4 weeks post-treatment (SVR4)

  post-treatment week 4

• Proportions of patients who achieve Sustained Virologic Response at 24 weeks post-treatment (SVR 24)

  post-treatment week 24

• Proportion of treated study participants prematurely discontinuing study treatment for any reason, proportion prematurely discontinuing treatment for lack of efficacy or for clinical adverse events or laboratory abnormalities

  during treatment and up to 24 weeks post-treatment

• Proportion of patients experiencing treatment-emergent adverse events, and proportion of patients experiencing adverse events considered to be probably or possibly related to one or more of the study drugs

  during treatment and up to 24 weeks post-treatment

Study Arms (6)

1a: Treatment-naive patients, without ribavirin (RBV)

EXPERIMENTAL

PPI-668 + sofosbuvir for 12 weeks

Drug: ravidasvir hydrochloride; Drug: sofosbuvir

1b: Treatment-naive patients, with RBV

EXPERIMENTAL

PPI-668 + sofosbuvir + ribavirin (RBV) for 12 weeks

Drug: ravidasvir hydrochloride; Drug: sofosbuvir; Drug: ribavirin

2a: Non-cirrhotic previous non-responders, without RBV

EXPERIMENTAL

PPI-668 + sofosbuvir for 12 weeks

Drug: ravidasvir hydrochloride; Drug: sofosbuvir

2b: Non-cirrhotic previous non-responders, with RBV

EXPERIMENTAL

PPI-668 + sofosbuvir + ribavirin for 12 weeks

Drug: ravidasvir hydrochloride; Drug: sofosbuvir; Drug: ribavirin

3a: Cirrhotic previous non-responders 12 weeks

EXPERIMENTAL

PPI-668 + sofosbuvir + ribavirin for 12 weeks

Drug: ravidasvir hydrochloride; Drug: sofosbuvir; Drug: ribavirin

3b: Cirrhotic previous non-responders 16 weeks

EXPERIMENTAL

PPI-668 + sofosbuvir + ribavirin for 16 weeks

Drug: ravidasvir hydrochloride; Drug: sofosbuvir; Drug: ribavirin

Interventions

ravidasvir hydrochloride DRUG

200 mg

Also known as: PPI-668

1a: Treatment-naive patients, without ribavirin (RBV); 1b: Treatment-naive patients, with RBV; 2a: Non-cirrhotic previous non-responders, without RBV; 2b: Non-cirrhotic previous non-responders, with RBV; 3a: Cirrhotic previous non-responders 12 weeks; 3b: Cirrhotic previous non-responders 16 weeks

sofosbuvir DRUG

400 mg

1a: Treatment-naive patients, without ribavirin (RBV); 1b: Treatment-naive patients, with RBV; 2a: Non-cirrhotic previous non-responders, without RBV; 2b: Non-cirrhotic previous non-responders, with RBV; 3a: Cirrhotic previous non-responders 12 weeks; 3b: Cirrhotic previous non-responders 16 weeks

ribavirin DRUG

1000 mg - 1200 mg per day, weight-based dosing

1b: Treatment-naive patients, with RBV; 2b: Non-cirrhotic previous non-responders, with RBV; 3a: Cirrhotic previous non-responders 12 weeks; 3b: Cirrhotic previous non-responders 16 weeks

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males or females, ≥ 18 years \& ≤ 65 years of age.
• HCV antibody positive, with serum HCV RNA ≥ 10,000 IU/mL, with clinical history compatible with chronic hepatitis C.
• HCV genotype-4 infection, confirmed at the central study laboratory
• Body mass index (BMI) between 18 and 35 kg/m2, inclusive.
• Both male and female patients who have childbearing potential must agree to practice an acceptable method of birth control during the study and for at least 6 months after the cessation of treatment; such contraceptive methods must include at least one barrier method.
• Patients for Group 1 must be treatment-naïve - i.e., they have never received any antiviral treatment for their HCV infection, including interferon, pegylated interferon, ribavirin, or other regulatory-approved or investigational HCV antiviral therapies.
• Patients for Groups 2 and 3 must have previously failed treatment with an interferon-based therapy - i.e., interferon or pegylated interferon, with or without ribavirin, with no other previous HCV antiviral therapies.
• Patients for Group 2 must be non-cirrhotic diagnosed on screening visit by both Fibroscan™ liver stiffness measurement \< 12.5 kPa and FIB-4 score \< 3.25 if the results of Fibroscan and FIB-4 score are not matching; liver biopsy will be used for detection of cirrhosis. In case that the liver biopsy is not applicable, hepatic imaging or ultrasound reports could be used for determination of cirrhosis.
• Patients for Group 3 must have underlying cirrhosis diagnosed on screening visit by both Fibroscan liver stiffness measurement \> 12.5 kPa and FIB-4 score \> 3.25, if the results of Fibroscan and FIB-4 score are not matching liver biopsy will be used for detection of cirrhosis. In case that the liver biopsy is not applicable, hepatic imaging or ultrasound reports could be used for determination of cirrhosis.
• Willing and able to give informed consent
• Willing and able to complete all study visits and procedures, including compliance with the requirements and restrictions listed in the consent form.

You may not qualify if:

• Mixed genotype or non-typable HCV genotype infection,
• Positive test for HBsAg or HIV antibody, or IgM antibody to HAV or HEV
• History of schistosomiasis or positive test for schistosoma surface antigen at Screen.
• Serum alpha-fetoprotein (AFP) \>100ng/ml. Patients with an AFP between 50 and 100ng/ml may be included as long as a liver ultrasound within 3 months of Screening, or at Screening, shows no evidence of potential hepatocellular cancer.
• Evidence of a medical condition other than HCV that is contributing to liver disease
• History of, or clinical signs of, hepatic decompensation or portal hypertension:
• Variceal bleeding, or documented esophageal or GI varices (at investigator discretion, patients suspected of having esophageal varices should be evaluated by endoscopy, and varices excluded) Ascites by history or on physical examination Documented or suspected hepatic encephalopathy
• Physical signs of portal hypertension:
• Clinically significant splenomegaly Spider angiomata History of porto-systemic shunt procedure(s)
• Uncontrolled diabetes mellitus as evidenced by HgbA1C ≥ 8.5% at Screening.
• Hemoglobin \< 11g/dL for females and \< 12 g/dL for males
• WBC count \< 3,500/mm3 OR absolute neutrophil count (ANC) \< 1800/mm
• Platelet count \< 75,000/mm3
• Serum creatinine \> 1.3 x ULN OR creatinine clearance (GFR) \< 50 mL/minute
• Serum ALT or AST \>10x ULN

Sponsors & Collaborators

• Pharco Pharmaceuticals: lead

Study Sites (3)

Al-Qahira Al-Fatimeya MoH Hospital

Cairo, Egypt

Location

Kasr El Aini Viral Hepatitis Center

Cairo, Egypt

Location

National Liver Institute

Menoufiya, Egypt

Location

Related Publications (1)

• Esmat G, Elbaz T, El Raziky M, Gomaa A, Abouelkhair M, Gamal El Deen H, Sabry A, Ashour M, Allam N, Abdel-Hamid M, Nada O, Helmy S, Abdel-Maguid H, Colonno R, Brown N, Ruby E, Vig P, Waked I. Effectiveness of ravidasvir plus sofosbuvir in interferon-naive and treated patients with chronic hepatitis C genotype-4. J Hepatol. 2017 Sep 19:S0168-8278(17)32286-9. doi: 10.1016/j.jhep.2017.09.006. Online ahead of print.

  PMID: 28935432 DERIVED

MeSH Terms

Conditions

Hepatitis C, Chronic

Interventions

ravidasvir; Sofosbuvir; Ribavirin

Condition Hierarchy (Ancestors)

Hepatitis C; Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Uridine Monophosphate; Uracil Nucleotides; Pyrimidine Nucleotides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleotides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleotides; Ribonucleosides; Nucleosides

Study Officials

• Gamal Esmat, M.D.

  Kasr El Aini Viral Hepatitis Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 1, 2015
• First Posted: February 25, 2015
• Study Start: January 1, 2015
• Primary Completion: January 1, 2016
• Study Completion: April 1, 2016
• Last Updated: April 7, 2016

Record last verified: 2015-10

Locations

EG (3)