Hepatitis CPhase 3PIONEERNCT03833362
Efficacy and Safety of Narlaprevir Used in Combination With Ritonavir in Treatment-Naïve and Failed Prior Treatment With Pegylated Interferon/Ribavirin Patients With Chronic Hepatitis C Genotype 1 (PIONEER - Study)
A Phase 3 study testing Narlaprevir, Ritonavir and Pegylated interferon alfa-2a/ Pegylated interferon alfa-2b in people with Hepatitis C, run by R-Pharm at 20 sites in Russia.
Trial summary
The purpose of this study was to confirm that combination of narlaprevir (NVR) and ritonavir (RTV) used as a metabolic inhibitor with pegylated interferon (PEG-INF) and ribavirin (RBV) leads to a superior Sustained Virological Response (SVR) rate compared to treatment with pegylated interferon and ribavirin in… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Hepatitis C
- What is being tested?
- Narlaprevir, Ritonavir and Pegylated interferon alfa-2a/ Pegylated interferon alfa-2b
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 420 participants
- Where
- 20 sitesRussia
- Study dates
- 7 May 2014to 21 Feb 2017
- Phase
- Phase 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Body weight ≥ 40 and ≤ 125 kg;
- Documented infection with HCV genotype 1 (Mixed infections with other genotypes are not eligible):
- treatment naïve (to interferon and ribavirin); or
- treatment failure patients (patients must have received interferon/ribavirin at standard doses for a minimum of 12 weeks);
- Minimum HCV-RNA level of ≥10,000 IU at baseline;
- No evidence of cirrhosis; availability at Baseline of at least one of the following tests negative results:
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- Liver biopsy showing no cirrhosis (not later than within 3 years prior to Baseline) or
- FibroScan elasticity score < 12.5 kPa 12 months prior to baseline or
- FibroTest < 0.75 12 months prior to baseline and aspartate aminotransferase (AST)/platelet ratio (APRI) of ≤ 1 during screening
- Using acceptable contraception methods for both partners from enrollment into the study until 6 months following the end of treatment;
- Willingness to give written informed consent.
Who cannot join
- Previous treatment with any HCV NS3-specific protease inhibitor and/ or other direct antiviral agents (e.g. HCV polymerase inhibitors);
- Treatment for HCV infection 30 days before the enrolment;
- Use of prohibited medications within 2 weeks prior to start of study medications (inducers or substrates of CYP3A4);
- Findings suspicious for hepatocellular carcinoma (HCC);
- Hepatic failure at present or in history;
- Auto-immune hepatitis in history;
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- Anti-nuclear antibodies (ANA) titers > 1:320;
- Evidence of gallstones, choledocholithiasis and calcified gallbladder;
- HBsAg positive;
- HIV positive;
- Serum hemoglobin of <13g/dL for males and <12g/dL for females;
- Neutrophils <1500/mm3 (<1,5х109/L) at Screening;
- Platelets <150000/mm3 (<150х109/L) at Screening (patients with a platelet count >100,000/mm3 (>100х109/L) but less than 150,000/mm3 (150х109/L) can be included in the study in case a Fibroscan or FibroTest or liver biopsy during the study screening period shows no cirrhosis)
- Total bilirubin >1.6 mg/dL (>27.36 µmol/L) unless history of Gilbert's disease. If Gilbert's disease is the proposed etiology, this must be documented in the subject's chart;
- Direct bilirubin >1.5 x upper limit of normal (ULN) of the laboratory reference range at Screening;
- Serum albumin < lower limit of normal (LLN) of laboratory reference range at Screening;
- Serum creatinine >ULN of the laboratory reference at Screening;
- Serum aspartate aminotransferase (AST) / alanine aminotransferase (ALT) >5 x ULN of the laboratory reference range at Screening;
- Thyroid stimulating hormone (TSH) >1.2 ULN or <0.8 LLN;
- Contraindications to pegylated interferon, ribavirin and/or ritonavir treatment;
- Hypersensitivity to any of the study drugs;
- Active or suspected cancer;
- Psychiatric disease (moderate or severe depression, schizophrenia, bipolar disorder et al);
- Previous suicide attempt or suicidal ideation;
- Drug addiction;
- Opiate agonist substitution therapy;
- History of active gout within the past year;
- Organ transplant (except of cornea and hair transplant);
- Pregnant or nursing women;
- Men whose female partners are pregnant or planning pregnancy;
- Any medical condition that could interfere with the patient's participation and completion of the study;
- Use of other investigational drugs/ participation in other clinical trial within 30 days before the enrolment.
Trial locations and contacts
20 sites in 1 country.
20 sites in 1 country
Russia20 sites
South-Ural State Medical University, Clinic of Medical Academy, Infectious Diseases Department
Chelyabinsk
Kazan State Medical Academy, Republican Clinical Hospital of Infectious Diseases n.a. A.F. Agafonov
Kazan'
Federal Budget Science Institution Central Science and Research Institute of Epidemiology of RosPotrebNadzor
Moscow
Federal State Budget Healthcare Institution Central Clinical Hospital of Russian Academy of Science
Moscow
First Moscow State Medical University n.a. I.M. Sechenov, Clinic of Nephrology, Internal and Professional Diseases n.a. E.M. Tarleev
Moscow
First Moscow State Medical University n.a. I.M. Sechenov, Propedeutics of Internal Diseases Department
Moscow
Moscow State Medical Stomatological University n.a. A. I. Evdokimov, Clinical Infectious Hospital #1, Clinical Infections Department
Moscow
Public Corporation "Clinical Hospital of Centrosouze"
Moscow
Public Corporation "MedElitConsulting"
Moscow
State Budget Healthcare Moscow Institution Clinical Scientific Center of Healthcare Department of Moscow
Moscow
State Budgetary Healthcare Organization Clinical city hospital #24
Moscow
Novosibirsk State Medical University, Clinical city hospital #12, Therapeutic Department
Novosibirsk
Military Medical Academy of Ministry of Defense of Russian Federation n.a. S.M. Kirov, Infectious Diseases Department
Saint Petersburg
Saint Petersburg State Budget Healthcare Institution Center of AIDS and Infectious Diseases Prevention and Control
Saint Petersburg
Saint Petersburg State Budgetary Healthcare Institution Clinical Hospital of Infectious Diseases n.a. S.P. Botkin
Saint Petersburg
Clinic of Samara State Medical University, Department of Infectious Diseases
Samara
Public corporation Medical company "Gepatolog"
Samara
Municipal Healthcare Institution Clinical city hospital #2 n.a. V.I. Razumovsky, Infectious Diseases Department
Saratov
Stavropolsky Krai Clinical Hospital, Gastroenterology Department related to Hospital Therapy Department
Stavropol
Stavropolsky State Medical University, Clinic of Gastroenterology, Hepatology and Pancreatology
Stavropol
About this study
Official title: International, Multicenter, Randomized, Double Blind, Active-controlled, Parallel-group Phase III Study of Narlaprevir/Ritonavir and Pegylated Interferon/Ribavirin in 2 Patient Populations - naïve and Treatment Failure Patients With Genotype 1 Chronic Hepatitis C
The purpose of this study was to confirm that combination of narlaprevir (NVR) and ritonavir (RTV) used as a metabolic inhibitor with pegylated interferon (PEG-INF) and ribavirin (RBV) leads to a superior Sustained Virological Response (SVR) rate compared to treatment with pegylated interferon and ribavirin in treatment-naïve and treatment failure patient populations.
Read the detailed description
The study included 3 time periods:
- Screening period with duration up to 3 weeks during which study eligibility was confirmed.
- Double-blind treatment period: all eligible patients divided into Treatment naive and Previous treatment failure subpopulations were randomized in one of the two parallel treatment arms in 2:1 ratio:
- Arm 1: All patients received the combination of NVR/RTV + PEG-INF/RBV for 12 weeks that was followed by PEG-INF and RBV for 12 weeks (total treatment duration of 24 weeks).
- Arm 2: Therapy with PEG-INF and RBV (standard of care) for 48 weeks with placebo equivalent for NVR and RTV for the first 12 weeks. Different types of pegylated interferon could be used for treatment. The assignment to the pegylated interferon alfa-2a or pegylated interferon alfa-2b treatment will be also performed using web system, in a 1:1 ratio. Clinical efficacy of each arm were assessed 24 weeks after the end of treatment with undetectable hepatitis C virus (HCV) RNA by lower limit of detection (LOD) 24 weeks following the end of treatment. In case of serum HCV-RNA levels were greater than or equal to 100 IU/mL at Week 12 of treatment (Arm 1) or serum HCV RNA declined from baseline less than 2 log after 12 weeks of treatment or serum HCV-RNA levels ≥LOD at week 24 of treatment (Arm 2) patients were considered non-responders and discontinued participation in the study. In case of satisfactory treatment response all patients were additionally administered with PEG-INF/RBV for 12 weeks (total of 24 weeks of treatment) in Arm 1, and for 36 weeks (total of 48 weeks of treatment) in Arm 2.
- Follow-up period during which patients do not receive any study medication. The duration of the follow-up period after the end of study treatment will be 24 weeks.
Overall, each patient will participate in the study for approximately up to 75 weeks from the time the patient signs the Informed Consent Form through the final visit
- Conditions
- Hepatitis C
- Being tested
- Narlaprevir, Ritonavir, Placebo Narlaprevir, Placebo Ritonavir, Pegylated interferon alfa-2a/ Pegylated interferon alfa-2b
- Medical subject headings
- Hepatitis C
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NarlaprevirDrug
yellow film-coated 100 mg. tablets
RitonavirDrug
Also called Norvir
100 mg tablets encapsulates in gelatin capsules (for blinding purposes)
Placebo NarlaprevirDrug
yellow film-coated 100 mg. tablets identical to Narlaprevir tablets
Placebo RitonavirDrug
100 mg lactose/ cellulose tablets encapsulated in gelatin capsules (for blinding purposes) identical to Ritonavir capsules
Pegylated interferon alfa-2a/ Pegylated interferon alfa-2bDrug
Also called Pegasys, PegIntron
180µg for subcutaneous injections in 0.5 ml syrettes / 1.5 µg/kg for subcutaneous injections in 50µkg, 80µkg,100µkg, 120µkg, 150µkg in vials
RibavirinDrug
Also called Rebetol
hard gelatin, white 200mg. capsules
Weight-based dose was 1000 mg/day (patient weight <75 kg) or 1200 mg/day (patient weight ≥75 kg) with Peginterferon alfa-2a and 800 mg/day (patient weight <65 kg) - 1400 (patient weight >105 kg) mg/day with Peginterferon alfa-2b
| Study group | Role | What they receive |
|---|---|---|
| NVR/RTV + PEG-INF/RBV (Treatment Naive) | Experimental | Narlaprevir - 2 tablets once a day orally
Ritonavir - 1 capsule once a day orally
Pegylated interferon alfa-2a/ Pegylated interferon alfa-2b - subcutaneous injection once weekly. Patients will be instructed by the investigator on how to self-administer the drug and will be given at each dispensing visit the quantity of PEG-INF alfa-2a and PEG-INF alfa-2b needed between visits.
Ribavirin - twice daily orally. In the case of co-administration with PEG-INF alfa-2a: 5 RBV capsules (2 in the morning + 3 in the evening) or 6 RBV capsules (3 in the morning + 3 in the evening) - weight based. In the case of co-administration with PEG-INF alfa-2b: 4 RBV capsules (2 in the morning + 2 in the evening) - minimal dose or 7 (3 in the morning + 4 in the evening) - maximal dose Receives: Drug: Narlaprevir; Drug: Ritonavir; Drug: Pegylated interferon alfa-2a/ Pegylated interferon alfa-2b; Drug: Ribavirin |
| PEG-INF/RBV (Treatment Naive) | Active comparator | Placebo Narlaprevir - 2 tablets once a day orally
Placebo Ritonavir - 1 capsule once a day orally
Pegylated interferon alfa-2a/ Pegylated interferon alfa-2b - subcutaneous injection once weekly. Patients will be instructed by the investigator on how to self-administer the drug and will be given at each dispensing visit the quantity of PEG-INF alfa-2a and PEG-INF alfa-2b needed between visits.
Ribavirin - twice daily orally. In the case of co-administration with PEG-INF alfa-2a: 5 RBV capsules (2 in the morning + 3 in the evening) or 6 RBV capsules (3 in the morning + 3 in the evening) - weight based. In the case of co-administration with PEG-INF alfa-2b: 4 RBV capsules (2 in the morning + 2 in the evening) - minimal dose or 7 (3 in the morning + 4 in the evening) - maximal dose Receives: Drug: Placebo Narlaprevir; Drug: Placebo Ritonavir; Drug: Pegylated interferon alfa-2a/ Pegylated interferon alfa-2b; Drug: Ribavirin |
| NVR/RTV + PEG-INF/RBV (Treatment Failure) | Experimental | Narlaprevir - 2 tablets once a day orally
Ritonavir - 1 capsule once a day orally
Pegylated interferon alfa-2a/ Pegylated interferon alfa-2b - subcutaneous injection once weekly. Patients will be instructed by the investigator on how to self-administer the drug and will be given at each dispensing visit the quantity of PEG-INF alfa-2a and PEG-INF alfa-2b needed between visits.
Ribavirin - twice daily orally. In the case of co-administration with PEG-INF alfa-2a: 5 RBV capsules (2 in the morning + 3 in the evening) or 6 RBV capsules (3 in the morning + 3 in the evening) - weight based. In the case of co-administration with PEG-INF alfa-2b: 4 RBV capsules (2 in the morning + 2 in the evening) - minimal dose or 7 (3 in the morning + 4 in the evening) - maximal dose Receives: Drug: Narlaprevir; Drug: Ritonavir; Drug: Pegylated interferon alfa-2a/ Pegylated interferon alfa-2b; Drug: Ribavirin |
| PEG-INF/RBV (Treatment Failure) | Active comparator | Placebo Narlaprevir - 2 tablets once a day orally
Placebo Ritonavir - 1 capsule once a day orally
Pegylated interferon alfa-2a/ Pegylated interferon alfa-2b - subcutaneous injection once weekly. Patients will be instructed by the investigator on how to self-administer the drug and will be given at each dispensing visit the quantity of PEG-INF alfa-2a and PEG-INF alfa-2b needed between visits.
Ribavirin - twice daily orally. In the case of co-administration with PEG alfa-2a: 5 RBV capsules (2 in the morning + 3 in the evening) or 6 RBV capsules (3 in the morning + 3 in the evening) - weight based. In the case of co-administration with PEG alfa-2b: 4 RBV capsules (2 in the morning + 2 in the evening) - minimal dose or 7 (3 in the morning + 4 in the evening) - maximal dose Receives: Drug: Placebo Narlaprevir; Drug: Placebo Ritonavir; Drug: Pegylated interferon alfa-2a/ Pegylated interferon alfa-2b; Drug: Ribavirin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of patients with Sustained Virologic Response (SVR24)
HCV RNA undetectable by Limit of detection (LOD)
Measured: Week 24 after the end of treatment
Secondary outcomes (8)
Number of patients who achieve the Rapid Virological Response (RVR)
HCV RNA < LOD
Measured: Week 4 of treatment
Number of patients who achieve the Early Virological Response (EVR)
HCV RNA <LOD
Measured: Week 12 of treatment
Number of patients who achieve the End of Treatment Response (ETR)
HCV RNA <LOD
Measured: Week 24 of treatment (Arm 1), Week 48 of treatment (Arm 2)
Number of patients who achieve the SVR12
HCV RNA undetectable (by LOD)
Measured: Week 12 after the end of treatment
Number of patients who develop viral breakthrough
Greater than or equal to 1 log10 increase in HCV-RNA above nadir, or detectable HCV-RNA, while on treatment after an initial drop below detection
Measured: Week 24 of treatment (Arm 1), Week 48 of treatment (Arm 2)
Number of patients who develop relapse
HCV RNA undetectable by LOD at end of treatment with subsequent detectable HCV RNA
Measured: Week 24 after the end of treatment
Number of patients who develop anemia
Anemia is defined as as Hb <10g/dL
Measured: Week 24 of treatment (Arm 1), Week 48 of treatment (Arm 2)
Number of patients who develop neutropenia
Neutropenia is defined as neutrophils <0.75x109/L
Measured: Week 24 of treatment (Arm 1), Week 48 of treatment (Arm 2)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Feb 2019
- Study start7 May 2014
- Primary completion23 Mar 2016
- Study completion21 Feb 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatitis CStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 420 participants (actual)
Sponsor and investigators
- Lead sponsor
- R-Pharm
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Mikhail Samsonov, Study director, R-Pharm
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03833362
- Sponsor's protocol ID
- CJ05013008
- Acronym
- PIONEER
- Status last verified
- Feb 2019
- First submitted
- 5 Feb 2019
- Last updated
- 7 Feb 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- International, Multicenter, Randomized, Double Blind, Active-controlled, Parallel-group Phase III Study of Narlaprevir/Ritonavir and Pegylated Interferon/Ribavirin in 2 Patient Populations - naïve and Treatment Failure Patients With Genotype 1 Chronic Hepatitis C
- ClinicalTrials.gov ID
- NCT03833362
- Acronym / sponsor ID
- PIONEER / CJ05013008
- Conditions
- Hepatitis C
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 420 participants (actual)
- Lead sponsor
- R-PharmIndustry (pharma, biotech, devices)
- Study start
- 7 May 2014 (actual)
- Primary completion
- 23 Mar 2016 (actual)
- Study completion
- 21 Feb 2017 (actual)
- First posted
- 7 Feb 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study was to confirm that combination of narlaprevir (NVR) and ritonavir (RTV) used as a metabolic inhibitor with pegylated interferon (PEG-INF) and ribavirin (RBV) leads to a superior Sustained Virological Response (SVR) rate compared to treatment with pegylated interferon and ribavirin in treatment-naïve and treatment failure patient populations.
Detailed description
The study included 3 time periods:
- Screening period with duration up to 3 weeks during which study eligibility was confirmed.
- Double-blind treatment period: all eligible patients divided into Treatment naive and Previous treatment failure subpopulations were randomized in one of the two parallel treatment arms in 2:1 ratio:
- Arm 1: All patients received the combination of NVR/RTV + PEG-INF/RBV for 12 weeks that was followed by PEG-INF and RBV for 12 weeks (total treatment duration of 24 weeks).
- Arm 2: Therapy with PEG-INF and RBV (standard of care) for 48 weeks with placebo equivalent for NVR and RTV for the first 12 weeks. Different types of pegylated interferon could be used for treatment. The assignment to the pegylated interferon alfa-2a or pegylated interferon alfa-2b treatment will be also performed using web system, in a 1:1 ratio. Clinical efficacy of each arm were assessed 24 weeks after the end of treatment with undetectable hepatitis C virus (HCV) RNA by lower limit of detection (LOD) 24 weeks following the end of treatment. In case of serum HCV-RNA levels were greater than or equal to 100 IU/mL at Week 12 of treatment (Arm 1) or serum HCV RNA declined from baseline less than 2 log after 12 weeks of treatment or serum HCV-RNA levels ≥LOD at week 24 of treatment (Arm 2) patients were considered non-responders and discontinued participation in the study. In case of satisfactory treatment response all patients were additionally administered with PEG-INF/RBV for 12 weeks (total of 24 weeks of treatment) in Arm 1, and for 36 weeks (total of 48 weeks of treatment) in Arm 2.
- Follow-up period during which patients do not receive any study medication. The duration of the follow-up period after the end of study treatment will be 24 weeks.
Overall, each patient will participate in the study for approximately up to 75 weeks from the time the patient signs the Informed Consent Form through the final visit
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| NVR/RTV + PEG-INF/RBV (Treatment Naive) | Experimental | Drug: Narlaprevir, Drug: Ritonavir, Drug: Pegylated interferon alfa-2a/ Pegylated interferon alfa-2b, Drug: RibavirinNarlaprevir - 2 tablets once a day orally Ritonavir - 1 capsule once a day orally Pegylated interferon alfa-2a/ Pegylated interferon alfa-2b - subcutaneous injection once weekly. Patients will be instructed by the investigator on how to self-administer the drug and will be given at each dispensing visit the quantity of PEG-INF alfa-2a and PEG-INF alfa-2b needed between visits. Ribavirin - twice daily orally. In the case of co-administration with PEG-INF alfa-2a: 5 RBV capsules (2 in the morning + 3 in the evening) or 6 RBV capsules (3 in the morning + 3 in the evening) - weight based. In the case of co-administration with PEG-INF alfa-2b: 4 RBV capsules (2 in the morning + 2 in the evening) - minimal dose or 7 (3 in the morning + 4 in the evening) - maximal dose |
| PEG-INF/RBV (Treatment Naive) | Active comparator | Drug: Placebo Narlaprevir, Drug: Placebo Ritonavir, Drug: Pegylated interferon alfa-2a/ Pegylated interferon alfa-2b, Drug: RibavirinPlacebo Narlaprevir - 2 tablets once a day orally Placebo Ritonavir - 1 capsule once a day orally Pegylated interferon alfa-2a/ Pegylated interferon alfa-2b - subcutaneous injection once weekly. Patients will be instructed by the investigator on how to self-administer the drug and will be given at each dispensing visit the quantity of PEG-INF alfa-2a and PEG-INF alfa-2b needed between visits. Ribavirin - twice daily orally. In the case of co-administration with PEG-INF alfa-2a: 5 RBV capsules (2 in the morning + 3 in the evening) or 6 RBV capsules (3 in the morning + 3 in the evening) - weight based. In the case of co-administration with PEG-INF alfa-2b: 4 RBV capsules (2 in the morning + 2 in the evening) - minimal dose or 7 (3 in the morning + 4 in the evening) - maximal dose |
| NVR/RTV + PEG-INF/RBV (Treatment Failure) | Experimental | Drug: Narlaprevir, Drug: Ritonavir, Drug: Pegylated interferon alfa-2a/ Pegylated interferon alfa-2b, Drug: RibavirinNarlaprevir - 2 tablets once a day orally Ritonavir - 1 capsule once a day orally Pegylated interferon alfa-2a/ Pegylated interferon alfa-2b - subcutaneous injection once weekly. Patients will be instructed by the investigator on how to self-administer the drug and will be given at each dispensing visit the quantity of PEG-INF alfa-2a and PEG-INF alfa-2b needed between visits. Ribavirin - twice daily orally. In the case of co-administration with PEG-INF alfa-2a: 5 RBV capsules (2 in the morning + 3 in the evening) or 6 RBV capsules (3 in the morning + 3 in the evening) - weight based. In the case of co-administration with PEG-INF alfa-2b: 4 RBV capsules (2 in the morning + 2 in the evening) - minimal dose or 7 (3 in the morning + 4 in the evening) - maximal dose |
| PEG-INF/RBV (Treatment Failure) | Active comparator | Drug: Placebo Narlaprevir, Drug: Placebo Ritonavir, Drug: Pegylated interferon alfa-2a/ Pegylated interferon alfa-2b, Drug: RibavirinPlacebo Narlaprevir - 2 tablets once a day orally Placebo Ritonavir - 1 capsule once a day orally Pegylated interferon alfa-2a/ Pegylated interferon alfa-2b - subcutaneous injection once weekly. Patients will be instructed by the investigator on how to self-administer the drug and will be given at each dispensing visit the quantity of PEG-INF alfa-2a and PEG-INF alfa-2b needed between visits. Ribavirin - twice daily orally. In the case of co-administration with PEG alfa-2a: 5 RBV capsules (2 in the morning + 3 in the evening) or 6 RBV capsules (3 in the morning + 3 in the evening) - weight based. In the case of co-administration with PEG alfa-2b: 4 RBV capsules (2 in the morning + 2 in the evening) - minimal dose or 7 (3 in the morning + 4 in the evening) - maximal dose |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Body weight ≥ 40 and ≤ 125 kg;
- Documented infection with HCV genotype 1 (Mixed infections with other genotypes are not eligible):
- Minimum HCV-RNA level of ≥10,000 IU at baseline;
- No evidence of cirrhosis; availability at Baseline of at least one of the following tests negative results:
- Using acceptable contraception methods for both partners from enrollment into the study until 6 months following the end of treatment;
Key exclusion criteria (32 listed)
- Previous treatment with any HCV NS3-specific protease inhibitor and/ or other direct antiviral agents (e.g. HCV polymerase inhibitors);
- Treatment for HCV infection 30 days before the enrolment;
- Use of prohibited medications within 2 weeks prior to start of study medications (inducers or substrates of CYP3A4);
- Findings suspicious for hepatocellular carcinoma (HCC);
- Hepatic failure at present or in history;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Narlapreviryellow film-coated 100 mg. tablets | Drug | NVR/RTV + PEG-INF/RBV (Treatment Failure), NVR/RTV + PEG-INF/RBV (Treatment Naive) |
| RitonavirAlso: Norvir100 mg tablets encapsulates in gelatin capsules (for blinding purposes) | Drug | NVR/RTV + PEG-INF/RBV (Treatment Failure), NVR/RTV + PEG-INF/RBV (Treatment Naive) |
| Placebo Narlapreviryellow film-coated 100 mg. tablets identical to Narlaprevir tablets | Drug | PEG-INF/RBV (Treatment Failure), PEG-INF/RBV (Treatment Naive) |
| Placebo Ritonavir100 mg lactose/ cellulose tablets encapsulated in gelatin capsules (for blinding purposes) identical to Ritonavir capsules | Drug | PEG-INF/RBV (Treatment Failure), PEG-INF/RBV (Treatment Naive) |
| Pegylated interferon alfa-2a/ Pegylated interferon alfa-2bAlso: Pegasys, PegIntron180µg for subcutaneous injections in 0.5 ml syrettes / 1.5 µg/kg for subcutaneous injections in 50µkg, 80µkg,100µkg, 120µkg, 150µkg in vials | Drug | NVR/RTV + PEG-INF/RBV (Treatment Failure), NVR/RTV + PEG-INF/RBV (Treatment Naive), PEG-INF/RBV (Treatment Failure), PEG-INF/RBV (Treatment Naive) |
| RibavirinAlso: Rebetolhard gelatin, white 200mg. capsules Weight-based dose was 1000 mg/day (patient weight <75 kg) or 1200 mg/day (patient weight ≥75 kg) with Peginterferon alfa-2a and 800 mg/day (patient weight <65 kg) - 1400 (patient weight >105 kg) mg/day with Peginterferon alfa-2b | Drug | NVR/RTV + PEG-INF/RBV (Treatment Failure), NVR/RTV + PEG-INF/RBV (Treatment Naive), PEG-INF/RBV (Treatment Failure), PEG-INF/RBV (Treatment Naive) |
Primary outcome
Number of patients with Sustained Virologic Response (SVR24)
Time frame: Week 24 after the end of treatment
HCV RNA undetectable by Limit of detection (LOD)
8 secondary outcomes
Number of patients who achieve the Rapid Virological Response (RVR)
Time frame: Week 4 of treatment
Number of patients who achieve the Early Virological Response (EVR)
Time frame: Week 12 of treatment
Number of patients who achieve the End of Treatment Response (ETR)
Time frame: Week 24 of treatment (Arm 1), Week 48 of treatment (Arm 2)
Number of patients who achieve the SVR12
Time frame: Week 12 after the end of treatment
Number of patients who develop viral breakthrough
Time frame: Week 24 of treatment (Arm 1), Week 48 of treatment (Arm 2)
Number of patients who develop relapse
Time frame: Week 24 after the end of treatment
Number of patients who develop anemia
Time frame: Week 24 of treatment (Arm 1), Week 48 of treatment (Arm 2)
Number of patients who develop neutropenia
Time frame: Week 24 of treatment (Arm 1), Week 48 of treatment (Arm 2)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Feb 2019.
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HCV Infection
Active, not recruitingPhase 4
People With CHC Who Achieved a Sustained Virological Response Following Therapy With Direct Acting Antiviral Agents
Diabetes Mellitus, Hepatitis C, Chronic
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mikhail Samsonov study director
R-Pharm
20 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Narlaprevir, Ritonavir and Pegylated interferon alfa-2a/ Pegylated interferon alfa-2b in people with Hepatitis C, run by R-Pharm at 20 sites in Russia.
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: finished, as of the sponsor's last update on 7 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 sites in Russia. 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 phase mean?
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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Number of patients with Sustained Virologic Response (SVR24) (time frame: Week 24 after the end of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 Feb 2019.