Myrcludex B Plus Pegylated Interferon-alpha-2a in Patients With HBeAg Negative HBV/HDV Co-infection

• Sponsor: Hepatera Ltd. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02637999
• Collaborator: (none)
• Enrollment: 24
• Arms: 3
• Actual Duration (Months): 23.2

Study Details

Study Description

Brief Summary

Randomized open-label substudy of daily Myrcludex B (MXB) plus pegylated interferon-alpha-2a (PEG-INF-a) in patients with hepatitis B e antigen (HBeAg) negative chronic hepatitis B virus (HBV) co-infected with hepatitis delta virus (HDV).

Condition or Disease	Intervention/Treatment	Phase
Chronic Hepatitis D Infection	Drug: PEG IFN alfa-2a; Drug: Myrcludex B	Phase 1/Phase 2

Detailed Description

The study is designed to evaluate safety and efficacy of MXB in a subset of HBV infected patients who are co-infected with HDV. Hepatitis delta represents the most severe form of chronic viral hepatitis and there is no approved treatment option available for patients infected with both HBV and HDV.

24 patients will be randomised into 3 arms: pre-treatment with MXB followed by PEG-INF-a treatment versus a combination of both drugs versus PEG-INF-a.

Prolonged blockade of HBV entry into hepatocytes should also block infection with HDV particles (which uses hepatitis B surface antigen (HBsAg) as its envelope) and thus provide a therapeutic option for this otherwise hardly treatable disease. PEG-INF-a is used for the treatment of chronic hepatitis delta. The study endpoints are virological response (HBsAg, hepatitis delta virus ribonucleic acid (HDV RNA), hepatitis B virus deoxyribonucleic acid (HBV DNA)), as well as safety and tolerability and drug immunogenicity.

Study Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Randomized Open-label Substudy of Daily Myrcludex B Plus Pegylated Interferon-alpha-2a in Patients With HBeAg Negative Chronic Hepatitis B Co-infected With Hepatitis Delta
• Actual Study Start Date: Feb 13, 2014
• Actual Primary Completion Date: Jan 21, 2016
• Actual Study Completion Date: Jan 21, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: MXB then PEG IFN Myrcludex B 2mg daily for 24 weeks, followed by PEG IFN alfa-2a 180 µg/0.5 mL weekly for 48 weeks	Drug: PEG IFN alfa-2a; Other Names: Pegasys ; Drug: Myrcludex B; Other Names: Myrcludex
Experimental: MXB + PEG IFN then PEG IFN Myrcludex B 2mg daily and PEG IFN alfa-2a 180 µg/0.5 mL weekly for 24 weeks, followed by PEG IFN alfa-2a 180 µg/0.5 mL weekly for 24 weeks	Drug: PEG IFN alfa-2a; Other Names: Pegasys ; Drug: Myrcludex B; Other Names: Myrcludex
Active Comparator: PEG IFN PEG IFN alfa-2a 180 µg/0.5 mL once weekly for 48 weeks	Drug: PEG IFN alfa-2a; Other Names: Pegasys

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Hepatitis B Surface Antigen (HBsAg) Response at Week 12 of Therapy [Baseline and 12 weeks]

   HBsAg response was defined as serum HBsAg decline of at least 0.5 log IU/mL (or HBsAg negativation) at week 12 compared to baseline (including the patient with negative baseline level)

Secondary Outcome Measures

1. Number of Participants With Hepatitis B Surface Antigen (HBsAg) Response at Week 24 of Therapy [Baseline and 24 weeks]

   HBsAg response was defined as serum HBsAg decline of at least 0.5 log IU/mL (or HBsAg negativation) at week 24 compared to baseline (including the patient with negative baseline level)

2. Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) Response at Week 24 of Therapy [Baseline and 24 weeks]

   HBV DNA response was defined as persistent reduction of HBV DNA by > 1 log IU/mL or negativation (including the patient with negative baseline level)

3. Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) Response at Week 12 of Therapy [Baseline and 12 weeks]

   HBV DNA response was defined as persistent reduction of HBV DNA by > 1 log IU/mL or negativation (including the patient with negative baseline level)

4. Number of Participants With Hepatitis D Virus Ribonucleic Acid (HDV RNA) Response at Week 12 of Therapy [Baseline and 12 weeks]

   HDV RNA response was defined as persistent reduction of HDV RNA by > 1 log IU/mL or negativation (including the patient with negative baseline level)

5. Number of Participants With Hepatitis D Virus Ribonucleic Acid (HDV RNA) Response at Week 24 of Therapy [Baseline and 24 weeks]

   HDV RNA response was defined as persistent reduction of HDV RNA by > 1 log IU/mL or negativation (including the patient with negative baseline level)

6. Number of Participants With Biochemical Response at Week 12 of Therapy [Baseline and 12 weeks]

   Biochemical response was defined as normalization of ALT level as compared to baseline.

7. Number of Participants With Biochemical Response at Week 24 of Therapy [Baseline and 24 weeks]

   Biochemical response was defined as normalization of ALT level as compared to baseline.

8. Number of Participants With Covalently Closed Circular Deoxyribonucleic Acid (cccDNA) Response at Week 72 of Therapy [Baseline and 72 weeks for arm A and 48 weeks for arms B and C]

   Virological cccDNA response was defined as reduction of intrahepatic cccDNA by 0.5 log in comparison to baseline at the end of follow up.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Chronic hepatitis B defined by the presence of HBsAg for at least 6 months prior to screening period. Co-infection with hepatitis D virus defined as positive anti-HDV antibodies for at least 3 months and positive for HDV-RNA within the screening period.

• Liver biopsy performed within one year prior to screening or during screening period.

• HBeAg negative

• All women of childbearing potential must have a negative urine pregnancy test prior to enrolment.

• Women must:

1. Be menopausal for at least 2 years, or

2. Be surgically sterile (total hysterectomy or bilateral ovariectomy or bilateral tubal ligation/clips or otherwise be incapable of pregnancy), or

3. Not be heterosexually active during the study, or

4. Agree to use a highly effective method of birth control (double barrier method or combination of barrier method with hormonal or intrauterine device) during the study and for 3 month after the last dosing of the investigational medicinal product.

• Men must agree to use a highly effective method of birth control (double barrier methods or combination of barrier method with hormonal or intrauterine device in their women-partner) and not to donate a sperm during the study and for 3 month after the last dosing of the investigational medicinal product.

• An understanding, ability and willingness to fully comply with study procedures and restrictions.

• An ability to provide the written informed consent to participate in the study

Exclusion Criteria:

• Decompensated liver disease (Child-Pugh-Score >6).

• Co-infected with hepatitis C virus (HCV), or HIV.

• Patients with presence of anti-HCV antibody and negative HCV RNA in two separate occasions within 12 months prior to screening could be enrolled into the study after sponsor written permission.

• ALT > 6 ULN.

• Creatinine clearance < 60 mL/min.

• Total bilirubin > 2 mg/dL.

• Confirmed contraindication for treatment with PEG-INF-a.

• History of hepatocellular carcinoma (HCC) or findings suggestive of possible HCC, such as suspicious foci on imaging studies or elevated serum alpha-fetoprotein (AFP) levels. In patients with such findings, HCC will be ruled-out prior to screening for the present study.

• One or more additional known primary or secondary causes of liver disease, other than hepatitis B (e.g., alcoholism, autoimmune hepatitis, malignancy with hepatic involvement, hemochromatosis, alpha-1 antitrypsin deficiency, Wilson's Disease, other congenital or metabolic conditions affecting the liver, e.g. congestive heart failure or other severe cardiopulmonary disease). Patients with Gilbert's syndrome and Dubin-Johnson syndrome, two benign disorders associated with low-grade hyperbilirubinemia can be enrolled into the trial.

• History of clinically evident pancreatitis.

• History of alcohol or drug abuse within the preceding two years. For the purposes of the present study, alcohol abuse is arbitrarily defined as frequent consumption of alcoholic beverages with an average daily intake of more than 40 g of ethanol.

• Participation in another study with an investigational drug within less than one month prior to this study or simultaneously to this study.

• Patients who are unable or unwilling to follow the protocol requirements.

• Patients with a history of seizures, central nervous system disorders or psychiatric disability thought to be clinically significant in the opinion of the investigator.

• Patients with limited mental capacity to the extent that she/he cannot provide informed consent or information regarding adverse events of the study drug.

• Clinically significant renal, respiratory or cardiovascular disease.

• Pregnancy and lactation.

• Patients who have previously participated in this study.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Hepatera Ltd.

Investigators

• Principal Investigator: Pavel Bogomolov, PhD, LLC "Clinical Hospital of Tsentrosoyuz"

Study Documents (Full-Text)

None provided.

More Information

Publications

• Blank A, Markert C, Hohmann N, Carls A, Mikus G, Lehr T, Alexandrov A, Haag M, Schwab M, Urban S, Haefeli WE. First-in-human application of the novel hepatitis B and hepatitis D virus entry inhibitor myrcludex B. J Hepatol. 2016 Sep;65(3):483-9. doi: 10.1016/j.jhep.2016.04.013. Epub 2016 Apr 27.
• Cornberg M, Protzer U, Dollinger MM, Petersen J, Wedemeyer H, Berg T, Jilg W, Erhardt A, Wirth S, Schirmacher P, Fleig WE, Manns MP. Prophylaxis, diagnosis and therapy of hepatitis B virus (HBV) infection: the German guidelines for the management of HBV infection. Z Gastroenterol. 2007 Dec;45(12):1281-328.
• Lavanchy D. Hepatitis B virus epidemiology, disease burden, treatment, and current and emerging prevention and control measures. J Viral Hepat. 2004 Mar;11(2):97-107. Review.
• Romeo R, Del Ninno E, Rumi M, Russo A, Sangiovanni A, de Franchis R, Ronchi G, Colombo M. A 28-year study of the course of hepatitis Delta infection: a risk factor for cirrhosis and hepatocellular carcinoma. Gastroenterology. 2009 May;136(5):1629-38. doi: 10.1053/j.gastro.2009.01.052. Epub 2009 Jan 29.
• Trauner M, Boyer JL. Bile salt transporters: molecular characterization, function, and regulation. Physiol Rev. 2003 Apr;83(2):633-71. Review.
• Yan H, Zhong G, Xu G, He W, Jing Z, Gao Z, Huang Y, Qi Y, Peng B, Wang H, Fu L, Song M, Chen P, Gao W, Ren B, Sun Y, Cai T, Feng X, Sui J, Li W. Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus. Elife. 2012 Nov 13;1:e00049. doi: 10.7554/eLife.00049. Erratum in: Elife. 2014;3:e05570.

• Responsible Party: Hepatera Ltd.
• ClinicalTrials.gov Identifier: NCT02637999
• Other Study ID Numbers: MYR 201 (HDV)
• First Posted: Dec 22, 2015
• Last Update Posted: Apr 13, 2018
• Last Verified: Apr 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Infections; Hepatitis A; Hepatitis D; Hepatitis D, Chronic; Hepatitis; Hepatitis, Chronic; Peginterferon alfa-2a; Interferon alpha-2

Study Results

Participant Flow

Arm/Group Title	MXB Then PEG IFN	MXB + PEG IFN Then PEG IFN	PEG IFN
Arm/Group Description	Myrcludex B 2mg daily for 24 weeks, followed by PEG IFN alfa-2a 180 µg/0.5 mL once weekly for 48 weeks	Myrcludex B 2mg daily and PEG IFN alfa-2a 180 µg/0.5 mL once weekly for 24 weeks, followed by PEG IFN alfa-2a 180 µg/0.5 mL once weekly for 24 weeks	PEG IFN alfa-2a 180 µg/0.5 mL once weekly for 48 weeks
Period Title: Overall Study
STARTED	8	8	8
COMPLETED	7	6	6
NOT COMPLETED	1	2	2

Baseline Characteristics

Arm/Group Title	MXB Then PEG IFN	MXB + PEG IFN Then PEG IFN	PEG IFN	Total
Arm/Group Description	Myrcludex B 2mg daily for 24 weeks, followed by PEG IFN alfa-2a 180 µg/0.5 mL once weekly for 48 weeks	Myrcludex B 2mg daily and PEG IFN alfa-2a 180 µg/0.5 mL once weekly for 24 weeks, followed by PEG IFN alfa-2a 180 µg/0.5 mL once weekly for 24 weeks	PEG IFN alfa-2a 180 µg/0.5 mL once weekly for 48 weeks	Total of all reporting groups
Overall Participants	8	8	8	24
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	8 100%	8 100%	8 100%	24 100%
>=65 years	0 0%	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	38.3 (10.05)	33.0 (4.87)	42.1 (10.23)	37.8 (9.19)
Sex: Female, Male (Count of Participants)
Female	3 37.5%	1 12.5%	2 25%	6 25%
Male	5 62.5%	7 87.5%	6 75%	18 75%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%
White	8 100%	8 100%	8 100%	24 100%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
Russia	8 100%	8 100%	8 100%	24 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Hepatitis B Surface Antigen (HBsAg) Response at Week 12 of Therapy
Description	HBsAg response was defined as serum HBsAg decline of at least 0.5 log IU/mL (or HBsAg negativation) at week 12 compared to baseline (including the patient with negative baseline level)
Time Frame	Baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

For the efficacy assessments the main analysis set was Full analysis set (FAS): All patients of the Safety set.

Arm/Group Title	MXB Then PEG IFN	MXB + PEG IFN Then PEG IFN	PEG IFN
Arm/Group Description	Myrcludex B 2mg daily for 24 weeks, followed by PEG IFN alfa-2a 180 µg/0.5 mL once weekly for 48 weeks	Myrcludex B 2mg daily and PEG IFN alfa-2a 180 µg/0.5 mL once weekly for 24 weeks, followed by pegINF 180mcg once weekly for 24 weeks	PEG IFN alfa-2a, 180 µg/0.5 mL once weekly for 48 weeks
Measure Participants	8	8	8
Count of Participants [Participants]	0 0%	0 0%	0 0%

2. Secondary Outcome

Title	Number of Participants With Hepatitis B Surface Antigen (HBsAg) Response at Week 24 of Therapy
Description	HBsAg response was defined as serum HBsAg decline of at least 0.5 log IU/mL (or HBsAg negativation) at week 24 compared to baseline (including the patient with negative baseline level)
Time Frame	Baseline and 24 weeks

Outcome Measure Data

Analysis Population Description

For the efficacy assessments the main analysis set was Full analysis set (FAS): All patients of the Safety set.

Arm/Group Title	MXB Then PEG IFN	MXB + PEG IFN Then PEG IFN	PEG IFN
Arm/Group Description	Myrcludex B 2mg daily for 24 weeks, followed by PEG IFN alfa-2a 180 µg/0.5 mL once weekly for 48 weeks	Myrcludex B 2mg daily and PEG IFN alfa-2a 180 µg/0.5 mL once weekly for 24 weeks, followed by pegINF 180mcg once weekly for 24 weeks	PEG IFN alfa-2a, 180 µg/0.5 mL once weekly for 48 weeks
Measure Participants	8	8	8
Count of Participants [Participants]	2 25%	1 12.5%	3 37.5%

3. Secondary Outcome

Title	Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) Response at Week 24 of Therapy
Description	HBV DNA response was defined as persistent reduction of HBV DNA by > 1 log IU/mL or negativation (including the patient with negative baseline level)
Time Frame	Baseline and 24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	MXB Then PEG IFN	MXB + PEG IFN Then PEG IFN	PEG IFN
Arm/Group Description	Myrcludex B 2mg daily for 24 weeks, followed by PEG IFN alfa-2a 180 µg/0.5 mL once weekly for 48 weeks	Myrcludex B 2mg daily and PEG IFN alfa-2a 180 µg/0.5 mL once weekly for 24 weeks, followed by pegINF 180mcg once weekly for 24 weeks	PEG IFN alfa-2a, 180 µg/0.5 mL once weekly for 48 weeks
Measure Participants	8	8	8
Count of Participants [Participants]	2 25%	6 75%	3 37.5%

4. Secondary Outcome

Title	Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) Response at Week 12 of Therapy
Description	HBV DNA response was defined as persistent reduction of HBV DNA by > 1 log IU/mL or negativation (including the patient with negative baseline level)
Time Frame	Baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

For the efficacy assessments the main analysis set was Full analysis set (FAS): All patients of the Safety set.

Arm/Group Title	MXB Then PEG IFN	MXB + PEG IFN Then PEG IFN	PEG IFN
Arm/Group Description	Myrcludex B 2mg daily for 24 weeks, followed by PEG IFN alfa-2a 180 µg/0.5 mL once weekly for 48 weeks	Myrcludex B 2mg daily and PEG IFN alfa-2a 180 µg/0.5 mL once weekly for 24 weeks, followed by pegINF 180mcg once weekly for 24 weeks	PEG IFN alfa-2a, 180 µg/0.5 mL once weekly for 48 weeks
Measure Participants	8	8	8
Count of Participants [Participants]	1 12.5%	5 62.5%	1 12.5%

5. Secondary Outcome

Title	Number of Participants With Hepatitis D Virus Ribonucleic Acid (HDV RNA) Response at Week 12 of Therapy
Description	HDV RNA response was defined as persistent reduction of HDV RNA by > 1 log IU/mL or negativation (including the patient with negative baseline level)
Time Frame	Baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

For the efficacy assessments the main analysis set was Full analysis set (FAS): All patients of the Safety set.

Arm/Group Title	MXB Then PEG IFN	MXB + PEG IFN Then PEG IFN	PEG IFN
Arm/Group Description	Myrcludex B 2mg daily for 24 weeks, followed by PEG IFN alfa-2a 180 µg/0.5 mL once weekly for 48 weeks	Myrcludex B 2mg daily and PEG IFN alfa-2a 180 µg/0.5 mL once weekly for 24 weeks, followed by pegINF 180mcg once weekly for 24 weeks	PEG IFN alfa-2a, 180 µg/0.5 mL once weekly for 48 weeks
Measure Participants	8	8	8
Count of Participants [Participants]	4 50%	5 62.5%	6 75%

6. Secondary Outcome

Title	Number of Participants With Hepatitis D Virus Ribonucleic Acid (HDV RNA) Response at Week 24 of Therapy
Description	HDV RNA response was defined as persistent reduction of HDV RNA by > 1 log IU/mL or negativation (including the patient with negative baseline level)
Time Frame	Baseline and 24 weeks

Outcome Measure Data

Analysis Population Description

For the efficacy assessments the main analysis set was Full analysis set (FAS): All patients of the Safety set.

Arm/Group Title	MXB Then PEG IFN	MXB + PEG IFN Then PEG IFN	PEG IFN
Arm/Group Description	Myrcludex B 2mg daily for 24 weeks, followed by PEG IFN alfa-2a 180 µg/0.5 mL once weekly for 48 weeks	Myrcludex B 2mg daily and PEG IFN alfa-2a 180 µg/0.5 mL once weekly for 24 weeks, followed by pegINF 180mcg once weekly for 24 weeks	PEG IFN alfa-2a, 180 µg/0.5 mL once weekly for 48 weeks
Measure Participants	8	8	8
Count of Participants [Participants]	7 87.5%	7 87.5%	7 87.5%

7. Secondary Outcome

Title	Number of Participants With Biochemical Response at Week 12 of Therapy
Description	Biochemical response was defined as normalization of ALT level as compared to baseline.
Time Frame	Baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

For the efficacy assessments the main analysis set was Full analysis set (FAS): All patients of the Safety set.

Arm/Group Title	MXB Then PEG IFN	MXB + PEG IFN Then PEG IFN	PEG IFN
Arm/Group Description	Myrcludex B 2mg daily for 24 weeks, followed by PEG IFN alfa-2a 180 µg/0.5 mL once weekly for 48 weeks	Myrcludex B 2mg daily and PEG IFN alfa-2a 180 µg/0.5 mL once weekly for 24 weeks, followed by pegINF 180mcg once weekly for 24 weeks	PEG IFN alfa-2a, 180 µg/0.5 mL once weekly for 48 weeks
Measure Participants	8	8	8
Count of Participants [Participants]	2 25%	2 25%	2 25%

8. Secondary Outcome

Title	Number of Participants With Biochemical Response at Week 24 of Therapy
Description	Biochemical response was defined as normalization of ALT level as compared to baseline.
Time Frame	Baseline and 24 weeks

Outcome Measure Data

Analysis Population Description

For the efficacy assessments the main analysis set was Full analysis set (FAS): All patients of the Safety set.

Arm/Group Title	MXB Then PEG IFN	MXB + PEG IFN Then PEG IFN	PEG IFN
Arm/Group Description	Myrcludex B 2mg daily for 24 weeks, followed by PEG IFN alfa-2a 180 µg/0.5 mL once weekly for 48 weeks	Myrcludex B 2mg daily and PEG IFN alfa-2a 180 µg/0.5 mL once weekly for 24 weeks, followed by pegINF 180mcg once weekly for 24 weeks	PEG IFN alfa-2a, 180 µg/0.5 mL once weekly for 48 weeks
Measure Participants	8	8	8
Count of Participants [Participants]	6 75%	1 12.5%	1 12.5%

9. Secondary Outcome

Title	Number of Participants With Covalently Closed Circular Deoxyribonucleic Acid (cccDNA) Response at Week 72 of Therapy
Description	Virological cccDNA response was defined as reduction of intrahepatic cccDNA by 0.5 log in comparison to baseline at the end of follow up.
Time Frame	Baseline and 72 weeks for arm A and 48 weeks for arms B and C

Outcome Measure Data

Analysis Population Description

No data to be reported due to absence of biopsy data. Biopsy data are unavailable because analyses were not performed

Arm/Group Title	MXB Then PEG IFN	MXB + PEG IFN Then PEG IFN	PEG IFN
Arm/Group Description	Myrcludex B 2mg daily for 24 weeks, followed by PEG IFN alfa-2a 180 µg/0.5 mL once weekly for 48 weeks	Myrcludex B 2mg daily and PEG IFN alfa-2a 180 µg/0.5 mL once weekly for 24 weeks, followed by pegINF 180mcg once weekly for 24 weeks	PEG IFN alfa-2a, 180 µg/0.5 mL once weekly for 48 weeks
Measure Participants	0	0	0

Adverse Events

Arm/Group Title	MXB Then PEG IFN		MXB + PEG IFN Then PEG IFN		PEG IFN
Arm/Group Description	Myrcludex B 2mg daily for 24 weeks, followed by PEG IFN alfa-2a 180 µg/0.5 mL once weekly for 48 weeks		Myrcludex B 2mg daily and PEG IFN alfa-2a 180 µg/0.5 mL once weekly for 24 weeks, followed by pegINF 180mcg once weekly for 24 weeks		PEG IFN alfa-2a, 180 µg/0.5 mL once weekly for 48 weeks
All Cause Mortality
	MXB Then PEG IFN		MXB + PEG IFN Then PEG IFN		PEG IFN
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	MXB Then PEG IFN		MXB + PEG IFN Then PEG IFN		PEG IFN
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/8 (0%)		0/8 (0%)
Other (Not Including Serious) Adverse Events
	MXB Then PEG IFN		MXB + PEG IFN Then PEG IFN		PEG IFN
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/8 (100%)		8/8 (100%)		8/8 (100%)
Blood and lymphatic system disorders
Leucopenia	7/8 (87.5%)	16	7/8 (87.5%)	11	7/8 (87.5%)	17
Neutropenia	7/8 (87.5%)	17	7/8 (87.5%)	15	7/8 (87.5%)	21
Thrombocytopenia	6/8 (75%)	21	5/8 (62.5%)	14	6/8 (75%)	20
Anaemia	2/8 (25%)	2	0/8 (0%)	0	0/8 (0%)	0
Eosinophilia	1/8 (12.5%)	1	0/8 (0%)	0	0/8 (0%)	0
General disorders
Influenza like illness	5/8 (62.5%)	5	2/8 (25%)	2	3/8 (37.5%)	3
Fatigue	2/8 (25%)	2	0/8 (0%)	0	4/8 (50%)	4
Pyrexia	0/8 (0%)	0	2/8 (25%)	2	1/8 (12.5%)	1
Dizziness	1/8 (12.5%)	1	0/8 (0%)	0	0/8 (0%)	0
Investigations
Alanine aminotransferase increased	7/8 (87.5%)	11	3/8 (37.5%)	4	3/8 (37.5%)	6
Aspartate aminotransferase increased	6/8 (75%)	6	3/8 (37.5%)	5	3/8 (37.5%)	4
Gama-glutamyltransferase increased	1/8 (12.5%)	1	2/8 (25%)	3	2/8 (25%)	5
APTT prolonged	0/8 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0
Bilirubin increased	0/8 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0
Electrocardiogram QT prolonged	1/8 (12.5%)	1	0/8 (0%)	0	0/8 (0%)	0
Nervous system disorders
Irritability	1/8 (12.5%)	1	0/8 (0%)	0	1/8 (12.5%)	1
Skin and subcutaneous tissue disorders
Rash	0/8 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.