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CompletedNCT01380938WRITEUpdated Mar 24, 2022

Different Ribavirin Dosages and Different Duration of Treatment in Combination With PegInterferon in Patients With Genotype 2 and 3 (WRITE)

A Phase 3 interventional study of Peginterferon alpha-2a + Ribavirin in Chronic Hepatitis, sponsored by Casa Sollievo della Sofferenza IRCCS. Completed at 35 sites in Italy. Open to participants aged 18 Years to 70 Years. Per ClinicalTrials.gov, last updated 2022-03-24.

Sponsored by Casa Sollievo della Sofferenza IRCCS · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
1,150
Allocation
Randomized
Ages
18 Years to 70 Years
Sex
All
01

Study summary

WRITE study aim at identifying the effectiveness of an innovative individualized schedule of treatment as compared to standard regimen in patients with chronic HCV genotype 2 and 3.

Read the detailed description

The investigators are going to compare weight-based dosages of ribavirin, in combination with Peginterferon alpha-2a, with standard fixed dosages of 800 mg. Patients will be evaluated at week 4 with an assay of sensitivity of 15 IU/ml. Patients with week 4 response will discontinue treatment at week 12 in both arms. Patients with HCV RNA still detectable at week 4 and receiving 1000-1200 mg of ribavirin in arm A will discontinue treatment at week 24, whereas patients with HCV RNA still detectable at week 4 and receiving 800 mg of ribavirin in arm B will be treated till week 48.

A standard treatment arm (C) including patients treated for 24 weeks with Peginterferon alpha-2a and fixed 800 mg ribavirin dosage will be used as control arm.

02

Conditions studied

  • Chronic Hepatitis

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Keywords

  • genotypes 2 and 3
  • combination treatment
  • individualized treatment
03

Who can participate

Ages eligible
18 Years to 70 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Patients with chronic hepatitis C virus (HCV) infection (both HCVAb and HCV RNA positive)
  • Patients with HCV genotype 2 or 3
  • Age 18-70 years
  • Naïve patients or previously treated only with standard interferon monotherapy
  • Female patients of childbearing age who agree to avoid pregnancy during the period of treatment and 24 weeks after the end of treatment

Exclusion criteria

Exclusion Criteria:

  • Previous treatment with ribavirin
  • Cirrhosis (CHILD PUGH B and C)
  • Evidence of Hepatocellular carcinoma
  • Pregnancy
  • Retinopathy class I or II
  • Alcohol consumption > 40 gr/day
  • Chronic cardiac or respiratory diseases
  • HIV or HBsAg or HDV positivity
  • Hemoglobin \< 8.5 gr/dL
  • WBC \< 3.500/mm3
  • PLT \< 80.000/mm3
04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Single (Investigator)
Enrollment
1,150 participants (actual)

Study arms

  • No intervention
    Arm C. Standard duration

    Patients will be randomly assigned in 3:3:1 ratio to three treatment arms. In the standard treatment group (Arm C), patients will be treated for 24 weeks independently of the HCV RNA status at week 4 with Peginterferon alpha-2a at a dose of 180 mcg weekly in combination with oral ribavirin administered at a dosage of 800 mg/day. Patients enrolled in Arm C will be treated for standard 24 weeks duration of treatment.

  • Experimental
    Arm A

    Patients enrolled in Arm A will receive Peginterferon alpha-2a at a dosage of 180 mcg weekly in combination with oral ribavirin administered at a dosage of 1000 mg/day for patients with a body weight \< 75 kg or 1200 mg/day for those with a body weight \> 75 kg. Patients with week 4 viral clearance (labelled as rapid virological responders, RVR) will be allocated to 12 week treatment duration (Arm A), whereas those without RVR will be treated for 24 weeks (Arm A)

    Drug: Peginterferon alpha-2a + Ribavirin

  • Experimental
    Arm B

    Patients enrolled in Arm B will receive Peginterferon alpha-2a at a dosage of 180 mcg weekly in combination with oral ribavirin administered at a dosage of 800 mg/day. Patients with week 4 viral clearance (labelled as rapid virological responders, RVR) will be allocated to 12 week treatment duration (Arm B), whereas those without RVR will be treated for 48 weeks (Arm B)

    Drug: Peginterferon alpha-2a + Ribavirin

Interventions

  • DrugPeginterferon alpha-2a + Ribavirin

    Administration of ribavirin at a dosage of 1000 or 1200 mg per day based on body weight \< or \> 75 kg for 24 weeks (Arm A). Treatment duration of 48 weeks with standard fixed dose of ribavirin (800 mg/day) (Arm B). These schedules will be compared with diagram of standard therapy with 800 mg daily of ribavirin for 24 weeks (Arm C)

    Also known as: Peginterferon alpha-2a (40 kD) PEGASYS, Copegus or Rebetol, Ribavirin Teva

05

What researchers measure

Primary outcomes

  1. Sustained virological Response (SVR)

    The primary measure of efficacy will be HCV RNA not detectable in serum samples 24 weeks after the end of therapy (SVR).

    Time frame: 6 months after the end of treatment

Secondary outcomes

  1. Rapid virological response (RVR)

    proportion of patients with undetectable HCV RNA 4 weeks after the start of treatment

    Time frame: On treatment week 4

06

Study locations

35 sites
  • Infectious Diseases Unit
    Avellino, Italy
  • Clinical Medicine Unit "Mater Dei"
    Bari, Italy
  • Università di Bari
    Bari, Italy
  • Medicine Unit
    Barletta, Italy
  • Infectious Diseases Unit "V. Emanuele"
    Bisceglie, Italy
  • Medicine Unit
    Canosa di Puglia, Italy
  • Hepatology Unit
    Casarano, Italy
  • IRCCS "De Bellis"
    Castellana, Italy
  • Hepatology Unit
    Catania, Italy
  • Infectious Diseases Unit
    Catania, Italy
  • Gastroenterology Unit
    Como, Italy
  • Gastroenterology Unit Arcispedale "S. Anna"
    Ferrara, Italy
  • Gastroenterology Unit
    Firenze, Italy
  • Internal Medicine University of Firenze
    Firenze, Italy
  • Gastroenterology Unit
    Foggia, Italy
  • Infectious Diseases
    Foggia, Italy
  • Gastroenterology Unit
    Galatina, Italy
  • Infectious Diseases
    Lucca, Italy
  • Gastroenterology Unit
    Mottola, Italy
  • Gastroenterology Unit "Cardarelli"
    Napoli, Italy
  • USL Napoli 1
    Napoli, Italy
  • Hospital "V. Cervello"
    Palermo, Italy
  • Medical Clinic University of Palermo
    Palermo, Italy
  • Infectious Diseases Unit IRCCS "San Matteo"
    Pavia, Italy
  • Campus Biomedico University
    Roma, Italy
  • Hepatology Unit "S. Pertini"
    Roma, Italy
  • Hepatology Unit "san Camillo"
    Roma, Italy
  • Ospedale "Villa Betania"
    Roma, Italy
  • IRCCS "L. Spallanzani"
    Rome, Italy
  • IRCCS "Casa Sollievo della Sofferenza"
    San Giovanni Rotondo, 71013, Italy
  • Infectious Diseases Unit Ospedale Civile
    Sassari, Italy
  • Medicine Unit
    Sassari, Italy
  • Infectious Diseases
    Siracusa, Italy
  • SS. Annunziata
    Taranto, Italy
  • Medicine Unit
    Venosa, Italy
07

References and documents

Publications

  • Mangia A, Dalgard O, Minerva N, Verbaan H, Bacca D, Ring-Larsen H, Copetti M, Carretta V, Piazzolla V, Cozzolongo R, Mottola L, Andriulli A. Ribavirin dosage in patients with HCV genotypes 2 and 3 who completed short therapy with peg-interferon alpha-2b and ribavirin. Aliment Pharmacol Ther. 2010 Jun;31(12):1346-53. doi: 10.1111/j.1365-2036.2010.04290.x. Epub 2010 Mar 8. PubMed 20222909 ↗
  • Mangia A, Minerva N, Bacca D, Cozzolongo R, Agostinacchio E, Sogari F, Scotto G, Vinelli F, Ricci GL, Romano M, Carretta V, Petruzzellis D, Andriulli A. Determinants of relapse after a short (12 weeks) course of antiviral therapy and re-treatment efficacy of a prolonged course in patients with chronic hepatitis C virus genotype 2 or 3 infection. Hepatology. 2009 Feb;49(2):358-63. doi: 10.1002/hep.22679. PubMed 19072829 ↗
  • Andriulli A, Mangia A, Iacobellis A, Ippolito A, Leandro G, Zeuzem S. Meta-analysis: the outcome of anti-viral therapy in HCV genotype 2 and genotype 3 infected patients with chronic hepatitis. Aliment Pharmacol Ther. 2008 Aug 15;28(4):397-404. doi: 10.1111/j.1365-2036.2008.03763.x. Epub 2008 Jun 11. PubMed 18549461 ↗
  • Mangia A, Santoro R, Minerva N, Ricci GL, Carretta V, Persico M, Vinelli F, Scotto G, Bacca D, Annese M, Romano M, Zechini F, Sogari F, Spirito F, Andriulli A. Peginterferon alfa-2b and ribavirin for 12 vs. 24 weeks in HCV genotype 2 or 3. N Engl J Med. 2005 Jun 23;352(25):2609-17. doi: 10.1056/NEJMoa042608. PubMed 15972867 ↗
08

Registry details

Key details

Study ID
NCT01380938
Lead sponsor
Casa Sollievo della Sofferenza IRCCS
Collaborators
Casa di Cura Mater Dei, IRCCS L. Spallanzani, Ospedale Francesco Ferrari, Azienda Ospedaliero Universitaria di Sassari, Fondazione IRCCS Policlinico San Matteo di Pavia, Arcispedale S. Anna, Ferrara, Azienda Ospedaliero-Universitaria, Catania, Ospedale di Venosa, Ospedale Monsignor R. Dimiccoli, Barletta, IRCCS De Bellis, Castellana, USL Napoli 1, Ospedale San Giuseppe Moscati, Avellino, Cardarelli Hospital, Ospedale Civile Vittorio Emanuele II, Bisceglie, Azienda Ospedaliero-Universitaria Careggi, Azienda Ospedaliera V. Cervello, Ospedale Civile Spirito Santo, Ospedale di Canosa di Puglia, University of Palermo, San Camillo Hospital, Rome, Campus Bio-Medico University, Ospedale Sandro Pertini, Roma, Ospedali Riuniti di Foggia, Ospedale SS. Annunziata, Taranto, Ospedale di Mottola, Ospedale Santa Caterina Novella, Galatina, University of Florence, Ospedale Valduce, Como, University of Bari, Azienda Ospedaliera, Siracusa, Azienda Ospedaliera, Lucca
Responsible party
Alessandra Mangia (MD, Casa Sollievo della Sofferenza IRCCS) — Principal investigator
First posted
Jun 27, 2011
Start date
Dec 1, 2018
Primary completion
Nov 30, 2019
Completion
Nov 30, 2019
Last update
Mar 24, 2022

Study contacts

Alessandra Mangia, MD
study director · IRCCS "Casa Sollievo della Sofferenza"

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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