Chronic HepatitisPhase 3WRITENCT01380938
Different Ribavirin Dosages and Different Duration of Treatment in Combination With PegInterferon in Patients With Genotype 2 and 3 (WRITE)
A Phase 3 study testing Peginterferon alpha-2a + Ribavirin in people with Chronic Hepatitis, run by Casa Sollievo della Sofferenza IRCCS at 35 sites in Italy.
Trial 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 more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Chronic Hepatitis
- What is being tested?
- Peginterferon alpha-2a + Ribavirin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,150 participants
- Where
- 35 sitesItaly
- Study dates
- 1 Dec 2018to 30 Nov 2019
- 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
- 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
Who cannot join
- 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
Show all 11Show fewer
- Chronic cardiac or respiratory diseases
- HIV or HBsAg or HDV positivity
- Hemoglobin < 8.5 gr/dL
- WBC < 3.500/mm3
- PLT < 80.000/mm3
Trial locations and contacts
35 sites in 1 country.
35 sites in 1 country
Italy35 sites
Infectious Diseases Unit
Avellino
Clinical Medicine Unit "Mater Dei"
Bari
Università di Bari
Bari
Medicine Unit
Barletta
Infectious Diseases Unit "V. Emanuele"
Bisceglie
Medicine Unit
Canosa di Puglia
Hepatology Unit
Casarano
IRCCS "De Bellis"
Castellana Grotte
Hepatology Unit
Catania
Infectious Diseases Unit
Catania
Gastroenterology Unit
Como
Gastroenterology Unit Arcispedale "S. Anna"
Ferrara
Gastroenterology Unit
Florence
Internal Medicine University of Firenze
Florence
Gastroenterology Unit
Foggia
Infectious Diseases
Foggia
Gastroenterology Unit
Galatina
Infectious Diseases
Lucca
Gastroenterology Unit
Mottola
Gastroenterology Unit "Cardarelli"
Naples
USL Napoli 1
Naples
Hospital "V. Cervello"
Palermo
Medical Clinic University of Palermo
Palermo
Infectious Diseases Unit IRCCS "San Matteo"
Pavia
Campus Biomedico University
Roma
Hepatology Unit "S. Pertini"
Roma
Hepatology Unit "san Camillo"
Roma
Ospedale "Villa Betania"
Roma
IRCCS "L. Spallanzani"
Rome
IRCCS "Casa Sollievo della Sofferenza"
San Giovanni Rotondo, 71013
Infectious Diseases Unit Ospedale Civile
Sassari
Medicine Unit
Sassari
Infectious Diseases
Syracuse
SS. Annunziata
Taranto
Medicine Unit
Venosa
About this study
Official title: RCT Comparing Different Ribavirin Dosages and Durations of Treatment in Combination With Peginterferon in HCV Genotypes 2 and 3 (WRITE)
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.
- Conditions
- Chronic Hepatitis
- Being tested
- Peginterferon alpha-2a + Ribavirin
- Keywords
- genotypes 2 and 3, combination treatment, individualized treatment
- Medical subject headings
- Hepatitis, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Peginterferon alpha-2a + RibavirinDrug
Also called Peginterferon alpha-2a (40 kD) PEGASYS, Copegus or Rebetol, Ribavirin Teva
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)
| Study group | Role | What they receive |
|---|---|---|
| Arm C. Standard duration | No intervention | 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. |
| Arm A | Experimental | 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) Receives: Drug: Peginterferon alpha-2a + Ribavirin |
| Arm B | Experimental | 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) Receives: Drug: Peginterferon alpha-2a + Ribavirin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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
Measured: On treatment week 4
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jun 2011 (estimated)
- Study start1 Dec 2018
- Primary completion30 Nov 2019
- Study completion30 Nov 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Chronic HepatitisStudies 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
- Single blind
- Who is masked
- Investigator
- Enrolment
- 1,150 participants (actual)
Sponsor and investigators
- Lead sponsor
- Casa Sollievo della Sofferenza IRCCS
- Sponsor type
- University, hospital or other
- Collaborators
- Casa di Cura Mater Dei, IRCCS L. Spallanzani, Ospedale Francesco Ferrari, Azienda Ospedaliero Universitaria di Sassari, Fondazione IRCCS Policlinico San Matteo di Pavia, S. Anna Hospital, 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, Valduce Hospital, University of Bari, Azienda Ospedaliera, Siracusa, Azienda Ospedaliera, Lucca
- Responsible party
- Principal investigator, Alessandra Mangia, Casa Sollievo della Sofferenza IRCCS
- Investigators
- Alessandra Mangia, MD, Study director, IRCCS Casa Sollievo della Sofferenza
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01380938
- Sponsor's protocol ID
- EPAT-01-2010
- Acronym
- WRITE
- Status last verified
- Mar 2022
- First submitted
- 23 Jun 2011
- Last updated
- 24 Mar 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
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 20222909Mangia 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 19072829Andriulli 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 18549461Mangia 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
Study at a glance
From the registry record, last updated by the sponsor on 24 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- RCT Comparing Different Ribavirin Dosages and Durations of Treatment in Combination With Peginterferon in HCV Genotypes 2 and 3 (WRITE)
- ClinicalTrials.gov ID
- NCT01380938
- Acronym / sponsor ID
- WRITE / EPAT-01-2010
- Conditions
- Chronic Hepatitis
- Keywords
- genotypes 2 and 3, combination treatment, individualized treatment
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,150 participants (actual)
- Lead sponsor
- Casa Sollievo della Sofferenza IRCCSUniversity, hospital or other
- Collaborators
- Casa di Cura Mater Dei, IRCCS L. Spallanzani, Ospedale Francesco Ferrari, Azienda Ospedaliero Universitaria di Sassari, Fondazione IRCCS Policlinico San Matteo di Pavia, S. Anna Hospital, 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, Valduce Hospital, University of Bari, Azienda Ospedaliera, Siracusa, Azienda Ospedaliera, Lucca
- Study start
- 1 Dec 2018 (actual)
- Primary completion
- 30 Nov 2019 (actual)
- Study completion
- 30 Nov 2019 (actual)
- First posted
- 27 Jun 2011 (estimated)
- 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.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Arm C. Standard duration | No intervention | –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. |
| Arm A | Experimental | Drug: Peginterferon alpha-2a + RibavirinPatients 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) |
| Arm B | Experimental | Drug: Peginterferon alpha-2a + RibavirinPatients 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) |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (11 listed)
- Previous treatment with ribavirin
- Cirrhosis (CHILD PUGH B and C)
- Evidence of Hepatocellular carcinoma
- Pregnancy
- Retinopathy class I or II
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 |
|---|---|---|
| Peginterferon alpha-2a + RibavirinAlso: Peginterferon alpha-2a (40 kD) PEGASYS, Copegus or Rebetol, Ribavirin TevaAdministration 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) | Drug | Arm A, Arm B |
Primary outcome
Sustained virological Response (SVR)
Time frame: 6 months after the end of treatment
The primary measure of efficacy will be HCV RNA not detectable in serum samples 24 weeks after the end of therapy (SVR).
1 secondary outcome
Rapid virological response (RVR)
Time frame: On treatment week 4
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 24 Mar 2022.
- Background: PubMed 20222909Mangia 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.
- Background: PubMed 19072829Mangia 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.
- Background: PubMed 18549461Andriulli 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.
- Background: PubMed 15972867Mangia 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.
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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.
Alessandra Mangia, MD study director
IRCCS Casa Sollievo della Sofferenza
35 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 Peginterferon alpha-2a + Ribavirin in people with Chronic Hepatitis, run by Casa Sollievo della Sofferenza IRCCS at 35 sites in Italy.
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 5 inclusion and 11 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 24 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 35 sites in Italy. 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?
Sustained virological Response (SVR) (time frame: 6 months 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?
On the ClinicalTrials.gov record for NCT01380938, which also lists 4 linked publications.
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 24 Mar 2022.