A Study Evaluating Slow Response/Non-Rapid Response in Patients With Chronic Hepatitis C, Genotype 1, 2, 3 & 4 Treated With Pegasys (Peginterferon Alfa-2a) and Copegus (Ribavirin)

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01429792
• Collaborator: (none)
• Enrollment: 1,013
• Locations: 26
• Arm: 1
• Actual Duration (Months): 56.5
• Patients Per Site: 39
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

This multi-center study will evaluate the viral response in patients with chronic hepatitis C, genotype 1, 2, 3 & 4 on standard anti-viral treatment with Pegasys (peginterferon alfa-2a) and Copegus (ribavirin). Patients will receive weekly subcutaneous Pegasys plus daily oral Copegus for 24 weeks (genotype 2 & 3) or 48 weeks (genotype 1 & 4). Patients identified as slow responders/non-rapid virological responders will be eligible for an additional 24 weeks of treatment.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis C, Chronic	Drug: peginterferon alfa-2a [Pegasys]; Drug: ribavirin [Copegus]	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 1013 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multi-Center Study Evaluating the Rate of Genotype 1, 2, 3 & 4 Chronic Hepatitis C Patients With Slow Response / Non-rapid Viral Response to Anti-Viral Treatment of Pegasys (Peginterferon Alfa 2a) in Combination With Copegus (Ribavirin)
• Actual Study Start Date: Sep 25, 2008
• Actual Primary Completion Date: Jun 10, 2013
• Actual Study Completion Date: Jun 10, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Single Arm	Drug: peginterferon alfa-2a [Pegasys]; standard treatment, subcutaneously weekly; Drug: ribavirin [Copegus]; standard treatment, orally daily

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Partial Early Virological Response (pEVR) to Study Treatment [Week 12]

   The rate of participants with pEVR to study treatment was defined as ≥ 2 log reduction in HCV-RNA level from baseline value to Week 12 of study treatment but with detectable HCV-RNA at Week 12.

2. Percentage of Participants With Complete Early Virologic Response (cEVR) to Study Treatment [Week 12]

   The rate of participants with a cEVR to study treatment was defined as negative HCV-RNA level at Week 12 of study treatment

3. Percentage of Participants With Undetectable HCV-RNA at End of Treatment Response (ETR) at Week 24 [Week 24]

   The rate of participants with undetectable HCV-RNA at ETR at Week 24 was defined as at least a 2-log decrement in HCV-RNA from the start of treatment, but with detectable HCV-RNA at Week 12 of study treatment and undetectable HCV-RNA at Week 24 of study treatment

4. Percentage of Participants With Rapid Virologic Response (RVR) at Week 4 [Week 4]

   The rate of participants with RVR was defined as negative HCV-RNA level at Week 4 of study treatment.

5. Percentage of Participants Without a RVR (Non-RVR) at Week 4 of Standard Treatment [Week 4]

   The rate of participants without a RVR (non-RVR) was defined as detectible HCV-RNA level at Week 4 of standard treatment.

6. Percentage of Participants With Non-RVR and Undetectable HCV-RNA at Week 24 [Week 24]

   The rate of participants with non-RVR and undetectable HCV-RNA at Week 24 was defined as detectable HCV-RNA level at Week 4 of study treatment and undetectable HCV-RNA at Week 24 of study.

Secondary Outcome Measures

1. Percentage of Participants With pEVR to Study Treatment at Week 12 [Week 12]

   The rate of participants with pEVR to study treatment was defined as ≥ 2 log reduction in HCV-RNA level from baseline value to Week 12 of study treatment but with detectable HCV-RNA at Week 12.

2. Percentge of Participants With a cEVR to Study Treatmen at Week 12 of Study Treatment [Week 12]

   The rate of participants with a cEVR to study treatment was defined as negative HCV-RNA level at Week 12 of study treatment.

3. Percentage of Participants With Undetectable HCV-RNA at Week 24, But With Detectable HCV-RNA atWeek 12 and Undetectable HCV-RNA at Week 24 [Week 24]

   The rate of participants with undetectable HCV-RNA at ETR at Week 24 was defined as at least a 2-log decrement in HCV-RNA from the start of treatment, but with detectable HCV-RNA at Week 12 of study treatment and undetectable HCV-RNA at Week 24 of study treatment.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Adult patients, >/= 18 years of age

• Serologic evidence of chronic hepatitis C, genotype 1, 2, 3 or 4 by anti-HCV antibody test

• Documented pre-treatment HCV RNA quantitative result

• Compensated liver disease (Child-Pugh Grade A)

• Patient receiving standard combination treatment of Pegasys (peginterferon alfa-2a and Copegus (ribavirin)

Exclusion Criteria:

• Decompensated liver disease (Child-Pugh Class B or C cirrhosis)

• Co-infection with active hepatitis A and/or hepatitis B

• History or evidence of a medical condition associated with liver disease other than HCV

• Signs and symptoms of hepatocellular carcinoma

• History of poorly controlled thyroid disease, elevated TSH or any clinical manifestations of thyroid disease

• Therapy with antineoplastic treatment </= 6 months prior to study day

• Diabetes mellitus in subjects receiving an insulin therapy

• Evidence of severe retinopathy

• Pregnant or breast-feeding women, and male partners of women who are pregnant

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Haemek Hospital; Gastroenterology	Afula		Israel	18101
2	Clalit City Ashdod MC; Liver Clinic	Ashdod		Israel	77444
3	Barzilai MC; Gastroenterology	Ashkelon		Israel	78278
4	Batyamon; Liver Unit	Bat Yam		Israel
5	Soroka Medical Center; Liver Unit	Beer Sheva		Israel	8410101
6	Soroka Medical Center; Gastroenterology	Beer Sheva		Israel	84105
7	Rambam Medical Center; Gastroenterology - Liver Unit	Haifa		Israel	31096
8	Bnei-Zion Medical Center; Gastroenterology	Haifa		Israel	33394
9	Carmel Hospital; Liver Unit	Haifa		Israel	34362
10	Wolfson Hospital; Gastroenterology Unit	Holon		Israel	58100
11	Hadassah Hospital; Liver Unit	Jerusalem		Israel	91120
12	Clalit Strauss MC	Jerusalem		Israel	95146
13	Meir Medical Center; Gastroenterology	Kfar Saba		Israel	44281
14	Naharyia / Western Galilee MC; Gastro Unit	Nahariya		Israel	22100
15	Holy Family Medical Center; Gastroenterology	Nazareth		Israel
16	Rabin Medical Center; Gastroenterology - Liver Unit	Petach Tikva		Israel	49100
17	Hasharon Mc; Gastroenterology	Petach Tikva		Israel
18	Chaim Sheba Medical Center; Gastroenterology	Ramat Gan		Israel	52621
19	Kaplan Medical Center; Gastroenterology Unit	Rehovot		Israel	76100
20	Clalit Pinsker Rishon; Liver Clinic	Rishon Lezion		Israel	75299
21	Rebecca Sieff; Gastroenterology	Safed		Israel	13110
22	Sourasky / Ichilov Hospital; Gastroenterology - Liver Unit	Tel Aviv		Israel	6423906
23	Clalit Zamenhoff	Tel Aviv		Israel	64353
24	Maccabi Health Services MC	Tel Aviv		Israel	67891
25	Poria Hospital; Gastroenterology	Tiberias		Israel
26	Assaf Harofeh; Gastroenterology	Zerifin		Israel	6093000

Sponsors and Collaborators

• Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT01429792
• Other Study ID Numbers: ML21779
• First Posted: Sep 7, 2011
• Last Update Posted: Oct 23, 2018
• Last Verified: Dec 1, 2017

• Additional relevant MeSH terms: Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis; Ribavirin; Peginterferon alfa-2a

Study Results

Participant Flow

Recruitment Details	Male and female participants, 18 years of age and above with serologically proven genotype 1, 2, 3 or 4 CHC and treated with the standard combination treatment of peginterferon alfa-2a (Pegasys) and ribavirin (Copegus).
Pre-assignment Detail	A total of 1013 participants were enrolled in the study and 607 of them completed the study.

Arm/Group Title	Pegylated Interferon Alfa 2a (Peginterferon)
Arm/Group Description	Participants with chronic hepatitis C (CHC) were treated with subcutaneous pegylated interferon once weekly in combination with ribavirin once daily.
Period Title: Overall Study
STARTED	1013
Genotype 1	687
Genotype 2 & 3	305
Genotype 4	5
COMPLETED	607
NOT COMPLETED	406

Baseline Characteristics

Arm/Group Title	Pegylated Interferon Alfa 2a (Peginterferon)
Arm/Group Description	Participants with chronic hepatitis C (CHC) were treated with subcutaneous pegylated interferon once weekly in combination with ribavirin once daily.
Overall Participants	1013
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	43.6 (11.3)
Sex/Gender, Customized (Number) [Number]
Female	380 37.5%
Male	632 62.4%
Unknown	1 0.1%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Partial Early Virological Response (pEVR) to Study Treatment
Description	The rate of participants with pEVR to study treatment was defined as ≥ 2 log reduction in HCV-RNA level from baseline value to Week 12 of study treatment but with detectable HCV-RNA at Week 12.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

Participants with CHC Genotype 1 & 4 at week 12

Arm/Group Title	Pegylated Interferon Alfa 2a (Peginterferon)
Arm/Group Description	Participants with chronic hepatitis C (CHC) were treated with subcutaneous pegylated interferon once weekly in combination with ribavirin once daily.
Measure Participants	692
Number (95% Confidence Interval) [Percentage of participants]	15.7 1.5%

2. Primary Outcome

Title	Percentage of Participants With Complete Early Virologic Response (cEVR) to Study Treatment
Description	The rate of participants with a cEVR to study treatment was defined as negative HCV-RNA level at Week 12 of study treatment
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

Participants with CHC Genotype 1 & 4 at Week 12

Arm/Group Title	Pegylated Interferon Alfa 2a (Peginterferon)
Arm/Group Description	Participants with chronic hepatitis C (CHC) were treated with subcutaneous pegylated interferon once weekly in combination with ribavirin once daily.
Measure Participants	692
Number (95% Confidence Interval) [Percentage of participants]	50.8 5%

3. Primary Outcome

Title	Percentage of Participants With Undetectable HCV-RNA at End of Treatment Response (ETR) at Week 24
Description	The rate of participants with undetectable HCV-RNA at ETR at Week 24 was defined as at least a 2-log decrement in HCV-RNA from the start of treatment, but with detectable HCV-RNA at Week 12 of study treatment and undetectable HCV-RNA at Week 24 of study treatment
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

Participants with CHC Genotype 1 & 4 at Week 24

Arm/Group Title	Pegylated Interferon Alfa 2a (Peginterferon)
Arm/Group Description	Participants with chronic hepatitis C (CHC) were treated with subcutaneous pegylated interferon once weekly in combination with ribavirin once daily.
Measure Participants	456
Number (95% Confidence Interval) [Percentage of participants]	15.6 1.5%

4. Primary Outcome

Title	Percentage of Participants With Rapid Virologic Response (RVR) at Week 4
Description	The rate of participants with RVR was defined as negative HCV-RNA level at Week 4 of study treatment.
Time Frame	Week 4

Outcome Measure Data

Analysis Population Description

Participants with CHC Genotype 2 & 3 at Week 4

Arm/Group Title	Pegylated Interferon Alfa 2a (Peginterferon)
Arm/Group Description	Participants with chronic hepatitis C (CHC) were treated with subcutaneous pegylated interferon once weekly in combination with ribavirin once daily.
Measure Participants	304
Number (95% Confidence Interval) [Percentage of participants]	48.03 4.7%

5. Primary Outcome

Title	Percentage of Participants Without a RVR (Non-RVR) at Week 4 of Standard Treatment
Description	The rate of participants without a RVR (non-RVR) was defined as detectible HCV-RNA level at Week 4 of standard treatment.
Time Frame	Week 4

Outcome Measure Data

Analysis Population Description

Participants with CHC Genotype 2 & 3 at Week 4

Arm/Group Title	Pegylated Interferon Alfa 2a (Peginterferon)
Arm/Group Description	Participants with chronic hepatitis C (CHC) were treated with subcutaneous pegylated interferon once weekly in combination with ribavirin once daily.
Measure Participants	304
Number (95% Confidence Interval) [Percentage of participants]	51.97 5.1%

6. Primary Outcome

Title	Percentage of Participants With Non-RVR and Undetectable HCV-RNA at Week 24
Description	The rate of participants with non-RVR and undetectable HCV-RNA at Week 24 was defined as detectable HCV-RNA level at Week 4 of study treatment and undetectable HCV-RNA at Week 24 of study.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

Participants with CHC Genotype 2 & 3 at Week 24

Arm/Group Title	Pegylated Interferon Alfa 2a (Peginterferon)
Arm/Group Description	Participants with chronic hepatitis C (CHC) were treated with subcutaneous pegylated interferon once weekly in combination with ribavirin once daily.
Measure Participants	305
Number (95% Confidence Interval) [Percentage of participants]	6.9 0.7%

7. Secondary Outcome

Title	Percentage of Participants With pEVR to Study Treatment at Week 12
Description	The rate of participants with pEVR to study treatment was defined as ≥ 2 log reduction in HCV-RNA level from baseline value to Week 12 of study treatment but with detectable HCV-RNA at Week 12.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

As pre-specified in the protocol, genotypes 1 and 4 were combined due to insufficient enrollment for genotype 4.

Arm/Group Title	Pegylated Interferon Alfa 2a (Peginterferon)
Arm/Group Description	Participants with chronic hepatitis C (CHC) were treated with subcutaneous pegylated interferon once weekly in combination with ribavirin once daily.
Measure Participants	0

8. Secondary Outcome

Title	Percentge of Participants With a cEVR to Study Treatmen at Week 12 of Study Treatment
Description	The rate of participants with a cEVR to study treatment was defined as negative HCV-RNA level at Week 12 of study treatment.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

As pre-specified in the protocol, genotypes 1 and 4 were combined due to insufficient enrollment for genotype 4.

Arm/Group Title	Pegylated Interferon Alfa 2a (Peginterferon)
Arm/Group Description	Participants with chronic hepatitis C (CHC) were treated with subcutaneous pegylated interferon once weekly in combination with ribavirin once daily.
Measure Participants	0

9. Secondary Outcome

Title	Percentage of Participants With Undetectable HCV-RNA at Week 24, But With Detectable HCV-RNA atWeek 12 and Undetectable HCV-RNA at Week 24
Description	The rate of participants with undetectable HCV-RNA at ETR at Week 24 was defined as at least a 2-log decrement in HCV-RNA from the start of treatment, but with detectable HCV-RNA at Week 12 of study treatment and undetectable HCV-RNA at Week 24 of study treatment.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

As pre-specified in the protocol, genotypes 1 and 4 were combined due to insufficient enrollment for genotype 4.

Arm/Group Title	Pegylated Interferon Alfa 2a (Peginterferon)
Arm/Group Description	Participants with chronic hepatitis C (CHC) were treated with subcutaneous pegylated interferon once weekly in combination with ribavirin once daily.
Measure Participants	0

Adverse Events

Time Frame	Baseline to Week 24
Adverse Event Reporting Description	Safety population includes all enrolled participants
Arm/Group Title	Pegylated Interferon Alfa 2a (Peginterferon)
Arm/Group Description	Participants with chronic hepatitis C (CHC) were treated with subcutaneous pegylated interferon once weekly in combination with ribavirin once daily.
All Cause Mortality
	Pegylated Interferon Alfa 2a (Peginterferon)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Pegylated Interferon Alfa 2a (Peginterferon)
	Affected / at Risk (%)	# Events
Total	50/1013 (4.9%)
Blood and lymphatic system disorders
Anemia	8/1013 (0.8%)
Haemolytic anemia	1/1013 (0.1%)
Neutropenic fever	1/1013 (0.1%)
Pancytopenia	3/1013 (0.3%)
Cardiac disorders
Acute myocardial infarction	2/1013 (0.2%)
Atrial fibrillation	1/1013 (0.1%)
Eye disorders
Optic nerve disorder	1/1013 (0.1%)
Optic Neuropathy	1/1013 (0.1%)
Retinal haemorrhage	1/1013 (0.1%)
Uveitis	1/1013 (0.1%)
Gastrointestinal disorders
Abdominal pain	1/1013 (0.1%)
Abdominal pain lower	1/1013 (0.1%)
pancreatitis	1/1013 (0.1%)
Pancreatitis acute	1/1013 (0.1%)
Vomiting	1/1013 (0.1%)
General disorders
Chest pain	1/1013 (0.1%)
Oedema Peripheral	1/1013 (0.1%)
Pyrexia	1/1013 (0.1%)
Asthenia	2/1013 (0.2%)
Hepatobiliary disorders
Jaundice cholestatic	1/1013 (0.1%)
Infections and infestations
Abdominal wall abcess	1/1013 (0.1%)
Appendicitis	2/1013 (0.2%)
Cellulitis	1/1013 (0.1%)
Pneumonia	3/1013 (0.3%)
Infection	1/1013 (0.1%)
Tubo-ovarian abcess	1/1013 (0.1%)
Urinary tract infection	3/1013 (0.3%)
Injury, poisoning and procedural complications
Foot fracture	1/1013 (0.1%)
Investigations
Hepatic enzyme increased	1/1013 (0.1%)
Metabolism and nutrition disorders
Diabetic ketoacidosis	1/1013 (0.1%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/1013 (0.1%)
Musculoskeletal pain	1/1013 (0.1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pancreatic neoplasm	1/1013 (0.1%)
Nervous system disorders
Cerebral hemorrhage	1/1013 (0.1%)
Polyneuropathy	1/1013 (0.1%)
Psychiatric disorders
Major depression	1/1013 (0.1%)
Reproductive system and breast disorders
Metrorrhagia	1/1013 (0.1%)
Scrotal swelling	1/1013 (0.1%)
Vaginal haemorrhage	1/1013 (0.1%)
Respiratory, thoracic and mediastinal disorders
Pneumonitis	1/1013 (0.1%)
Pulmonary embolism	1/1013 (0.1%)
Skin and subcutaneous tissue disorders
Skin ulcer	1/1013 (0.1%)
Surgical and medical procedures
Anal spincterotomy	1/1013 (0.1%)
Hernia repair	1/1013 (0.1%)
Inguinal hernia repair	1/1013 (0.1%)
Sigmoidectomy	1/1013 (0.1%)
Vascular disorders
Post thrombotic syndrome	1/1013 (0.1%)
Raynaud's phenomenon	1/1013 (0.1%)
Other (Not Including Serious) Adverse Events
	Pegylated Interferon Alfa 2a (Peginterferon)
	Affected / at Risk (%)	# Events
Total	131/1013 (12.9%)
Blood and lymphatic system disorders
Anemia	103/1013 (10.2%)
Neutropenia	57/1013 (5.6%)
General disorders
Asthenia	103/1013 (10.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.