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Chronic Hepatitis C Genotype 1bPhase 2NCT03485846

Efficacy and Safety of All-Oral Combination of Narlaprevir/Ritonavir and Daclatasvir in Treatment-Naїve Patients With Chronic Hepatitis C Genotype 1b

A Phase 2 study testing Narlaprevir, Ritonavir and Daclatasvir in people with Chronic Hepatitis C Genotype 1b, run by R-Pharm at 4 sites in Russia.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is to confirm that combination of Narlaprevir, Ritonavir and Daclatasvir is safe and highly effective regimen in treatment-naїve patients with chronic hepatitis C (HCV) genotype 1b infection. Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Chronic Hepatitis C Genotype 1b
What is being tested?
Narlaprevir, Ritonavir and Daclatasvir
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
105 participants
Where
4 sitesRussia
Study dates
27 Nov 2017to 21 Nov 2018
Phase
Phase 2
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

  • Subjects who meet all of the following criteria are eligible for participation in the study:
  • Are willing and able to provide written informed consent.
  • Have confirmed chronic HCV infection as documented by:
  • positive anti-HCV antibody (Ab) test or
  • positive HCV RNA or
  • positive HCV genotyping test at least 6 months prior to the Baseline/Day 1 visit.
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  • Have HCV genotype 1b at screening as determined by the Central Laboratory. Any non definitive results must exclude the subject from study participation.
  • 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:
  • Liver biopsy within 2 years of screening showing absence of cirrhosis;
  • Fibroscan with a result of ≤ 12.5 kPa within 6 months of baseline/Day1;
  • FibroTest score of ≤ 0.48 AND APRI of ≤ 1 performed during screening. In the absence of a definitive diagnosis of the presence or absence of cirrhosis by the above criteria, a liver biopsy was required. Liver biopsy results supersede the results obtained by Fibroscan or FibroTest.
  • Have a screening electrocardiogram (ECG) without clinically significant abnormalities (P wave < 0.1 s; PQ interval 0,12-0,2 s; QRS complex 0,06-0,1 s; QT interval 0,35-0,49 s).
  • Must have the following laboratory parameters at screening:
  • alanine aminotransferase (ALT) ≤ 10 x the upper limit of normal (ULN);
  • aspartate aminotransferase (AST) ≤ 10 x ULN;
  • Hemoglobin ≥ 12g/dL for male, ≥ 11g/dL for female subjects;
  • Platelets ≥ 50,000cells/mm3;
  • International normalized ratio (INR) ≤ 1.5 x ULN unless subject has known hemophilia or is stable on an anticoagulant regimen affecting INR;
  • Albumin ≥ 3g/dL;
  • Direct bilirubin ≤ 1.5 x ULN;
  • Hemoglobin A1c (HbA1c) ≤ 10%;
  • Creatinine clearance (CLcr) ≥ 60 mL/min, as calculated by the Cockcroft-Gault equation;
  • Have not been treated with any investigational drug or device within 30 days of the screening visit.
  • A female subject is eligible to enter the study if it is confirmed that she is:
  • Not pregnant or nursing;
  • Of non-childbearing potential (i.e., women who have had a hysterectomy, both ovaries removed, or medically documented ovarian failure, or are postmenopausal women >50 years of age with cessation [for ≥12 months] of previously occurring menses), or
  • Of childbearing potential (i.e., women who had not had a hysterectomy, both ovaries removed, or medically documented ovarian failure). Women ≤ 50 years of age with amenorrhea are considered to be of childbearing potential. These women must have a negative serum pregnancy test at screening and a negative urine pregnancy test on the baseline/Day 1 visit prior to enrollment. They must also agree to one of the following from 3 weeks prior to baseline/Day 1 until 6 months after last dose of the investigational drugs:
  • Complete abstinence from intercourse. Periodic abstinence from intercourse (e.g., calendar, ovulation, sympto thermal, post-ovulation methods) is not permitted Or
  • Consistent and correct use of 1 of the following methods of birth control listed below in addition to a male partner who correctly uses a condom from the date of screening until 6 months after the last dose of the investigational drugs:
  • intrauterine device (IUD) with a failure rate of < 1% per year;
  • female barrier method: cervical cap or diaphragm with spermicidal agent;
  • tubal sterilization;
  • vasectomy in male partner; Women of childbearing potential must not rely on hormone-containing contraceptives as a form of birth control during the study. Female subjects using a hormone-containing contraceptive prior to screening must stop their contraceptive regimen use from the date of screening until 6 months after their last dose of investigational drugs.
  • All male study participants must agree to consistently and correctly use a condom, while their female partner agrees to use either 1 of the non hormonal methods of birth control listed above or a hormone-containing contraceptive listed below, from the date of screening until 6 months after their last dose of investigational drugs:
  • implants of levonorgestrel;
  • injectable progesterone;
  • oral contraceptives (either combined or progesterone only);
  • contraceptive vaginal ring;
  • transdermal contraceptive patch;
  • Male subjects must agree to refrain from sperm donation for at least 6 months after the last dose of investigational drugs.
  • Are in generally good health as determined by the investigator.
  • Are able to comply with the dosing instructions for study drug administration and are able to complete the study schedule of assessments.

Who cannot join

  • Subjects with any of the following are not eligible for participation in the study:
  • Had prior exposure to IFN, RBV, or other approved or experimental DAA targeting the HCV.
  • Had prior exposure to amiodarone within 24 months before the screening
  • Are pregnant or nursing female or male with pregnant female partner.
  • Сhronic liver disease of a non-HCV etiology (e.g., hemochromatosis, Wilson's disease, α1-antitrypsin deficiency, cholangitis).
  • Are infected with hepatitis B virus (HBV) or human immunodeficiency virus (HIV).
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  • Have history of malignancy diagnosed or treated within 5 years; subjects under evaluation for malignancy are not eligible.
  • Have chronic use of systemically administered immunosuppressive agents (e.g., prednisone equivalent > 10 mg/day).
  • Have clinically relevant drug or alcohol abuse within 12 months of screening. A positive drug screen must exclude subjects unless it can be explained by a prescribed medication; the diagnosis and prescription must be approved by the investigator.
  • Have excessive alcohol consumption, defined as more than 3 drinks on any single day and more than 7 drinks per week for females, and > than 4 drinks on any single day and more than 14 drinks per week for males.
  • Have history of solid organ transplantation.
  • Have history of clinically significant illness or any other major medical disorder that may interfere with subject treatment, assessment, or compliance with the protocol by Investigators' opinion.
  • Have history of a gastrointestinal disorder (or postoperative condition) that can interfere with the absorption of the study drug.
  • Have history of difficulty with blood collection and/or poor venous access for the purposes of phlebotomy.
  • Usage of any prohibited concomitant medications as described in the protocol (list of drugs with expected drug-drug interactions due to concomitant ritonavir usage)
  • Have known hypersensitivity to the study investigational medicinal product, the metabolites, or formulation excipients.
  • Chronic HCV genotype 1b-infected participant who has the presence of genetic variants coding for the NS5A-Y93 С/H/N/S and/or L31 F/M/V/I amino acid substitutions at Screening.

Trial locations and contacts

4 sites in 1 country.

Russia4 sites

  • FBIS CSRI of Epidemiology of Federal Service on Customers

    Moscow

  • SBEI HPE Moscow State Medical and Dental University n.a. A.I. Evdokimov of Ministry of Health of Russia

    Moscow

  • SBHI of Moscow "City Clinical Hospital #24"

    Moscow

  • St. Petersburg SBHI Center of Prevention and Fight against AIDS and Infection Diseases

    Saint Petersburg

Other trials in Russia

About this study

Official title: Multicenter, Open-label, Phase II Safety and Efficacy Study of All-oral Combination Narlaprevir/Ritonavir and Daclatasvir Administered for 12 Weeks in Patients With Genotype 1b Chronic Hepatitis C

The purpose of this study is to confirm that combination of Narlaprevir, Ritonavir and Daclatasvir is safe and highly effective regimen in treatment-naїve patients with chronic hepatitis C (HCV) genotype 1b infection.

Read the detailed description

To evaluate effectiveness and safety of treatment with Narlaprevir, Ritonavir and Daclatasvir combination will be selected 105 treatment-naїve patients with chronic HCV genotype 1b without genetic variants coding for the NS5A-Y93 С/H/N/S and/or L31 F/M/V/I amino acid substitutions, eligible as per protocol criteria.

Each patient will participate in the trial approximately up to 38 weeks:

  • 2 weeks are expected for screening
  • up to 12 weeks for treatment period
  • 24 weeks for follow-up period

During treatment period all patient will receive equal drug combination.

Efficacy and safety parameters will be assessed as per primary and secondary endpoints. Also Ctrough for Narlaprevir and Daclatasvir on day 14 will be evaluated as pharmacokinetic objective.

The results of this study will provide new information about treatment of patients with chronic hepatitis C genotype 1 with Narlaprevir/Ritonavir in combination with Daclatasvir during 12 weeks.

Being tested
Narlaprevir, Ritonavir, Daclatasvir
Keywords
hepatitis C, chronic, 1b genotype, oral treatment
Medical subject headings
Hepatitis C, Bronchiolitis Obliterans Syndrome

What participants receive

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

  • NarlaprevirDrug

    Also called Arlansa

    100 mg, oval shaped, concave, yellow film-coated, tablets taken as 200 mg per os daily

  • RitonavirDrug

    Also called Norvir

    100 mg, tablets, taken as 100 mg per os daily

  • DaclatasvirDrug

    Also called Daklinza

    60 mg, tablets, taken as 60 mg per os daily

Study groups in NCT03485846
Study groupRoleWhat they receive
Narlaprevir + Ritonavir + DaclatasvirExperimentalAll of enrolled patients receive equal study therapy with Narlaprevir/Ritonavir/Daclatasvir daily for 12 weeks
Receives: Drug: Narlaprevir; Drug: Ritonavir; Drug: Daclatasvir

What is being measured

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

  1. The proportion of patients achieved Sustained Virologic Response (SVR12)

    SVR12 - Undetectable HCV RNA by lower limit of detection (LOD) 12 weeks following the end of treatment

    Measured: Week 12 of follow-up period

Secondary outcomes (5)

  1. The proportion of patients achieved Sustained Virologic Response (SVR24)

    SVR24 - Undetectable HCV RNA by (LOD) 24 weeks following the end of treatment

    Measured: Week 24 of follow-up period

  2. The proportion of patients achieved End of Treatment Response (ETR)

    ETR - HCV RNA < LOD at the treatment end

    Measured: Week 12 of treatment

  3. The proportion of patients achieved Sustained Virologic Response (SVR4)

    SVR4 - HCV RNA < LOD 4 weeks after the end of treatment

    Measured: Week 4 of follow-up period

  4. The proportion of patients developed Viral Breakthrough

    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 12 of treatment

  5. The proportion of patients Relapsed

    Relapse - HCV RNA undetectable by LOD at the end of treatment with subsequent detectable HCV RNA at the end of the follow-up period (week 12)

    Measured: Week 12 of follow-up period

Timeline

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

  1. First posted2 Apr 2018
  2. Study start27 Nov 2017
  3. Primary completion29 Aug 2018
  4. Study completion21 Nov 2018

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
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
105 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03485846
Sponsor's protocol ID
CJ05013046
Status last verified
Dec 2018
First submitted
2 Mar 2018
Last updated
19 Dec 2018
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Narlaprevir, Ritonavir and Daclatasvir in people with Chronic Hepatitis C Genotype 1b, run by R-Pharm at 4 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 43 inclusion and 17 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 19 Dec 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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?

The proportion of patients achieved Sustained Virologic Response (SVR12) (time frame: Week 12 of follow-up period). 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 NCT03485846.

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 19 Dec 2018.

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