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Chronic Hepatitis CPhase 2/3NCT02371408

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

A Phase 2/3 study testing ravidasvir hydrochloride, sofosbuvir and ribavirin in people with Chronic Hepatitis C, run by Pharco Pharmaceuticals at 3 sites in Egypt.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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. Treatment-naïve patients, with and without cirrhosis (Group 1) 2. Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Chronic Hepatitis C
What is being tested?
ravidasvir hydrochloride, sofosbuvir and ribavirin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
300 participants
Where
3 sitesEgypt
Study dates
Jan 2015to Apr 2016
Phase
Phase 2/3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
Show all 11Show fewer
  • 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.

Who cannot join

  • 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.
  • History of treatment with any investigational or regulatory-approved direct-acting antiviral (DAA) agent for HCV infection - nucleos(t)ide or non-nucleosidic HCV polymerase inhibitor, HCV protease inhibitor, NS5A inhibitor, or other antiviral agent for HCV infection other than pegylated -interferon and/or ribavirin Previous pegylated interferon and/or ribavirin treatment is allowed for Groups 2 and 3 but prohibited for group 1, as noted above in Inclusion criterion 6)
  • Evidence of a medical condition other than HCV that is contributing to liver disease
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  • 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
  • Serum albumin ≤ 3.2 g/dl
  • Direct serum bilirubin > 2xULN
  • INR > 1.7.
  • History of poorly controlled asthma, with one or more hospitalizations or emergency room visits in the previous 6 months
  • History of any malignancy within the last 5 years (except prostate cancer still within Glisson's capsule or basal cell carcinoma of the skin).
  • History of alcohol abuse as assessed by the investigator within the past 2 years, or an alcohol use pattern that may interfere with the patient's study compliance. Patients must have abstained from alcohol for at least 6 months prior to study start.
  • History of drug abuse as assessed by the investigator within the last 2 years.
  • Pregnancy, including current lactation in female patients, male patients with partners who are pregnant, or female patients intending to become pregnant.
  • Major surgery requiring overnight hospitalization within 3 months prior to Screening
  • Participation in another clinical trial of an investigational drug or device within 6 months prior to Screening
  • Current use or history of use within the preceding 6 months of immunosuppressive or immune-modulating agents, including: azathioprine, systemic corticosteroids (prednisone or prednisone equivalent of more than 10mg/day for more than 10 days), or other immunosuppressive agents. Use of inhaled steroids for mild/moderate asthma and topical steroids for minor skin conditions is allowed.
  • History of solid organ or bone marrow transplantation.
  • History of use of medications associated with QT prolongation concurrently or within the 30 days prior to Screening Visit, including: macrolides, antiarrhythmic agents, azoles, fluoroquinolones, and tricyclic anti-depressants.
  • correction, or a personal or family history of Torsades de Pointe.
  • Cardiac ischemia with history of recurrent angina, clinically symptomatic cardiac abnormalities, or requirement for cardiac pacemaker
  • History of a known allergy to ribavirin (RBV), or any excipient in the investigational product, or history of drug or other allergy that, in the opinion of the investigator, mitigates against study participation

Trial locations and contacts

3 sites in 1 country.

Egypt3 sites

  • Al-Qahira Al-Fatimeya MoH Hospital

    Cairo

  • Kasr El Aini Viral Hepatitis Center

    Cairo

  • National Liver Institute

    Menoufiya

Other trials in Egypt

About this study

Official title: A Phase IIb/IIIa, Randomized Study to Evaluate the Efficacy and Safety of PPI-668 (NS5A Inhibitor) Plus Sofosbuvir, With or Without Ribavirin, in Patients With Chronic Hepatitis C Genotype-4

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. Treatment-naïve patients, with and without cirrhosis (Group 1)
  2. Previous non-responders to interferon-based therapies, without cirrhosis (Group 2)
  3. Previous non-responders to interferon-based therapies, with cirrhosis (Group 3)
Being tested
ravidasvir hydrochloride, sofosbuvir, ribavirin
Medical subject headings
Hepatitis C, Chronic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ravidasvir hydrochlorideDrug

    Also called PPI-668

    200 mg

  • sofosbuvirDrug

    400 mg

  • ribavirinDrug

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

Study groups in NCT02371408
Study groupRoleWhat they receive
1a: Treatment-naive patients, without ribavirin (RBV)ExperimentalPPI-668 + sofosbuvir for 12 weeks
Receives: Drug: ravidasvir hydrochloride; Drug: sofosbuvir
1b: Treatment-naive patients, with RBVExperimentalPPI-668 + sofosbuvir + ribavirin (RBV) for 12 weeks
Receives: Drug: ravidasvir hydrochloride; Drug: sofosbuvir; Drug: ribavirin
2a: Non-cirrhotic previous non-responders, without RBVExperimentalPPI-668 + sofosbuvir for 12 weeks
Receives: Drug: ravidasvir hydrochloride; Drug: sofosbuvir
2b: Non-cirrhotic previous non-responders, with RBVExperimentalPPI-668 + sofosbuvir + ribavirin for 12 weeks
Receives: Drug: ravidasvir hydrochloride; Drug: sofosbuvir; Drug: ribavirin
3a: Cirrhotic previous non-responders 12 weeksExperimentalPPI-668 + sofosbuvir + ribavirin for 12 weeks
Receives: Drug: ravidasvir hydrochloride; Drug: sofosbuvir; Drug: ribavirin
3b: Cirrhotic previous non-responders 16 weeksExperimentalPPI-668 + sofosbuvir + ribavirin for 16 weeks
Receives: Drug: ravidasvir hydrochloride; Drug: sofosbuvir; Drug: ribavirin

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: post-treatment week 12

Secondary outcomes (4)

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

    Measured: post-treatment week 4

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

    Measured: post-treatment week 24

  3. 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

    Measured: during treatment and up to 24 weeks post-treatment

  4. 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

    Measured: during treatment and up to 24 weeks post-treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Feb 2015 (estimated)
  2. Study startJan 2015
  3. Primary completionJan 2016
  4. Study completionApr 2016 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
300 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02371408
Sponsor's protocol ID
PPI-668-202
Status last verified
Oct 2015
First submitted
1 Feb 2015
Last updated
7 Apr 2016
Results posted
No
Data monitoring committee
No

Publications

  • 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.

    PubMed 28935432

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing ravidasvir hydrochloride, sofosbuvir and ribavirin in people with Chronic Hepatitis C, run by Pharco Pharmaceuticals at 3 sites in Egypt.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 7 Apr 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Egypt. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Proportions of patients who achieve Sustained Virologic Response at 12 weeks post-treatment (SVR12) (time frame: post-treatment week 12). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02371408, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Apr 2016.

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