NCT02772744

Brief Summary

This is a prospective, cohort study in Faculty of Medicine, Zagazig University, Egypt. From June to December, 2016, investigators will follow up patients with chronic Hepatitis C virus genotype 4 receiving daclatasvir-sofosbuvir treatment regimen within the national program of Egyptian ministry of health and population. The primary outcomes are safety of the treatment and the sustained virologic response 12 weeks after discontinuation of therapy. For the secondary outcomes, investigators will measure the change in health related quality of life and investigate the genetic sequence of viral RNA of resistant patients.

Trial Health

35
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
250

participants targeted

Target at P75+ for all trials

Timeline
Completed

Started Nov 2017

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 24, 2016

Completed
2 months until next milestone

First Posted

Study publicly available on registry

May 13, 2016

Completed
1.5 years until next milestone

Study Start

First participant enrolled

November 1, 2017

Completed
1.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2018

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2018

Completed
Last Updated

October 10, 2017

Status Verified

October 1, 2017

Enrollment Period

1.2 years

First QC Date

March 24, 2016

Last Update Submit

October 8, 2017

Conditions

Hepatitis C

Keywords

Hepatitis C virus genotype 4AntiviralVirologic Response

Outcome Measures

Primary Outcomes (15)

  • Efficacy measured by Sustained Virologic Response Rate

    12 weeks posttreatment

  • Incidence of grade 3/4 adverse events [Safety]

    Within the treatment period (12 or 24 weeks according to the treatment regimen)

  • Incidence of Neutropenia [Safety]

    Neutropenia: Grade 3, 500-749/mm3; Grade 4, \<500/mm3

    Within the treatment period (12 or 24 weeks according to the treatment regimen)

  • Incidence of Lymphopenia [Safety]

    Lymphopenia: Grade 3, 350-499/mm3; Grade 4, \<350/mm3

    Within the treatment period (12 or 24 weeks according to the treatment regimen)

  • Incidence of anaemia [Safety]

    Anaemia: Grade 3, haemoglobin 7.0-8.9 g/dL; Grade 4, \<7.0 g/dL

    Within the treatment period (12 or 24 weeks according to the treatment regimen)

  • Incidence of Thrombocytopenia [Safety]

    Thrombocytopenia: Grade 3, 25 000-49 999/mm3; Grade 4, \<25 000/mm3

    Within the treatment period (12 or 24 weeks according to the treatment regimen)

  • Incidence of (Increased total Bilirubin) [Safety]

    Bilirubin elevations: Grade 3, 2.6-5×ULN; Grade 4, \>5×ULN

    Within the treatment period (12 or 24 weeks according to the treatment regimen)

  • Incidence of elevated Alanine Aminotransferase [Safety]

    Alanine Aminotransferase elevations: Grade 3, 5.1-10×upper limit of normal (ULN); Grade 4, \>10×ULN

    Within the treatment period (12 or 24 weeks according to the treatment regimen)

  • Incidence of Fatigue [Safety]

    Within the treatment period (12 or 24 weeks according to the treatment regimen)

  • Incidence of Headache [Safety]

    Within the treatment period (12 or 24 weeks according to the treatment regimen)

  • Incidence of Pruritus [Safety]

    Within the treatment period (12 or 24 weeks according to the treatment regimen)

  • Incidence of Insomnia [Safety]

    Within the treatment period (12 or 24 weeks according to the treatment regimen)

  • Incidence of Rash [Safety]

    Within the treatment period (12 or 24 weeks according to the treatment regimen)

  • Incidence of Nausea [Safety]

    Within the treatment period (12 or 24 weeks according to the treatment regimen)

  • Incidence of Myalgia [Safety]

    Within the treatment period (12 or 24 weeks according to the treatment regimen)

Secondary Outcomes (1)

  • Health Related Quality of Life (HRQoL)

    24 weeks

Study Arms (3)

Group 1: Easy to treat group

* Treatment naïve * Total serum bilirubin ≤ 1.2 mg/dl * Serum albumin ≥ 3.5 g/dl * International normalized ratio ≤ 1.2 * Platelet count ≥ 150000 mm3 This group will be receiving Sofosbuvir + daclatasvir for 12 weeks.

Drug: Daclatasvir 60 MG Oral Tablet [Daklinza]Drug: Sofosbuvir 400 MG Oral Tablet [Sovaldi]

Group 2: Difficult to treat group

* Peg interferon treatment experienced. * Total serum bilirubin ≥ 1.2 mg/dl * Serum albumin ≤ 3.5 g/dl * International normalized ratio ≥ 1.2 * Platelet count ≤ 150000 mm3 This group will be receiving Sofosbuvir + daclatasvir + ribavirin for 12 weeks.

Drug: Daclatasvir 60 MG Oral Tablet [Daklinza]Drug: Sofosbuvir 400 MG Oral Tablet [Sovaldi]Drug: Ribavirin Oral Product

Group 3: Sofosbuvir resistant cases

This is the group of patients who failed in previous Sofosbuvir treatment regiment. This group will be receiving Sofosbuvir + daclatasvir + ribavirin for 24 weeks.

Drug: Daclatasvir 60 MG Oral Tablet [Daklinza]Drug: Sofosbuvir 400 MG Oral Tablet [Sovaldi]Drug: Ribavirin Oral Product

Interventions

Daclatasvir 60 MG Oral Tablet [Daklinza]DRUG

Daclatasvir (60 MG) is a potent, pan-genotypic inhibitor of the HCV NS5A protein

Group 1: Easy to treat groupGroup 2: Difficult to treat groupGroup 3: Sofosbuvir resistant cases
Sofosbuvir 400 MG Oral Tablet [Sovaldi]DRUG

Sofosbuvir (400 MG) is a nucleotide analogue HCV NS5B polymerase inhibitor

Group 1: Easy to treat groupGroup 2: Difficult to treat groupGroup 3: Sofosbuvir resistant cases
Ribavirin Oral ProductDRUG

Ribavirin (twice-daily) dosed according to body weight (\<75 kg, 1000 mg daily; ≥75 kg, 1200 mg daily)

Group 2: Difficult to treat groupGroup 3: Sofosbuvir resistant cases

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

This study will include male or female patients ≥ 18 years, HCV RNA≥ 104 IU/mL, HCV genotype 4, screening ECG without clinically significant abnormalities.

You may qualify if:

  • Patients with HCV genotype 4
  • Age ≥ 18 years
  • HCV RNA≥ 104 IU/mL
  • Screening ECG without clinically significant abnormalities.

You may not qualify if:

  • Total serum bilirubin \> 3 mg/dl.
  • Serum albumin \< 2.8 g/dl.
  • INR ≥ 1.7
  • Platelet count \< 50000/mm3.
  • Hepatic cell carcinoma except four weeks after intervention aiming to cure with no evidence of activity by dynamic imaging (CT or MRI).
  • Extra hepatic malignancy except after two years of disease free interval
  • Pregnancy or inability to use contraception.
  • Inadequately controlled diabetes mellitus (HbA1c \> 9%).

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Related Publications (3)

  • Jensen D, Sherman KE, Hezode C, Pol S, Zeuzem S, de Ledinghen V, Tran A, Elkhashab M, Younes ZH, Kugelmas M, Mauss S, Everson G, Luketic V, Vierling J, Serfaty L, Brunetto M, Heo J, Bernstein D, McPhee F, Hennicken D, Mendez P, Hughes E, Noviello S; HALLMARK-QUAD Study Team. Daclatasvir and asunaprevir plus peginterferon alfa and ribavirin in HCV genotype 1 or 4 non-responders. J Hepatol. 2015 Jul;63(1):30-7. doi: 10.1016/j.jhep.2015.02.018. Epub 2015 Feb 19.

    PMID: 25703086BACKGROUND

  • Hezode C, Alric L, Brown A, Hassanein T, Rizzetto M, Buti M, Bourliere M, Thabut D, Molina E, Rustgi V, Samuel D, McPhee F, Liu Z, Yin PD, Hughes E, Treitel M; COMMAND-4 study team. Randomized controlled trial of the NS5A inhibitor daclatasvir plus pegylated interferon and ribavirin for HCV genotype-4 (COMMAND-4). Antivir Ther. 2015 Aug 27;21(3):195-205. doi: 10.3851/IMP2985. Online ahead of print.

    PMID: 26313445BACKGROUND

  • Wyles DL, Ruane PJ, Sulkowski MS, Dieterich D, Luetkemeyer A, Morgan TR, Sherman KE, Dretler R, Fishbein D, Gathe JC Jr, Henn S, Hinestrosa F, Huynh C, McDonald C, Mills A, Overton ET, Ramgopal M, Rashbaum B, Ray G, Scarsella A, Yozviak J, McPhee F, Liu Z, Hughes E, Yin PD, Noviello S, Ackerman P; ALLY-2 Investigators. Daclatasvir plus Sofosbuvir for HCV in Patients Coinfected with HIV-1. N Engl J Med. 2015 Aug 20;373(8):714-25. doi: 10.1056/NEJMoa1503153. Epub 2015 Jul 21.

    PMID: 26196502BACKGROUND

Related Links

MeSH Terms

Conditions

Hepatitis C

Interventions

daclatasvirTabletsSofosbuvir

Condition Hierarchy (Ancestors)

Blood-Borne InfectionsCommunicable DiseasesInfectionsHepatitis, Viral, HumanVirus DiseasesFlaviviridae InfectionsRNA Virus InfectionsHepatitisLiver DiseasesDigestive System Diseases

Intervention Hierarchy (Ancestors)

Dosage FormsPharmaceutical PreparationsUridine MonophosphateUracil NucleotidesPyrimidine NucleotidesPyrimidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsNucleotidesNucleic Acids, Nucleotides, and NucleosidesRibonucleotides

Study Officials

  • Samah A Loutfy

    National Cancer Institute, Cairo University, Cairo, Egypt

    STUDY DIRECTOR

Central Study Contacts

Ahmed Negida

CONTACT

+201125549087ahmed01251@medicine.zu.edu.eg

Hussien Ahmed, MD

CONTACT

+201006037334hoseen011232@medicine.zu.edu.eg

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER GOV
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Mr.

Study Record Dates

First Submitted

March 24, 2016

First Posted

May 13, 2016

Study Start

November 1, 2017

Primary Completion

December 31, 2018

Study Completion

December 31, 2018

Last Updated

October 10, 2017

Record last verified: 2017-10