A Study of Peginterferon Alfa-2a With or Without Ribavirin in Participants With Chronic Hepatitis D (CHD)

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02731131
• Collaborator: (none)
• Enrollment: 12
• Location: 1
• Arms: 2
• Duration (Months): 56
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This single-center, randomized, open-label, pilot study is designed to evaluate the efficacy and safety of 48 weeks of treatment with peginterferon alfa-2a alone versus in combination with ribavirin in participants with CHD.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis D, Chronic	Drug: Peginterferon alfa-2a; Drug: Ribavirin	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 12 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized, Pilot, Open-Label, Monocenter, Efficacy and Safety Study Examining the Effects of Peginterferon Alfa-2a (Pegasys) With or Without Ribavirin (Copegus) in Patients With Chronic Hepatitis D
• Study Start Date: Sep 1, 2004
• Actual Primary Completion Date: May 1, 2009
• Actual Study Completion Date: May 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group A: Monotherapy with Peginterferon alfa-2a Participants will receive peginterferon alfa-2a alone, administered over 48 weeks.	Drug: Peginterferon alfa-2a; Peginterferon alfa-2a will be administered as 180 micrograms (mcg) once weekly via subcutaneous (SC) injection.; Other Names: Pegasys
Experimental: Group B: Combination with Peginterferon alfa-2a + Ribavirin Participants will receive combination therapy with peginterferon alfa-2a plus ribavirin, administered over 48 weeks.	Drug: Peginterferon alfa-2a; Peginterferon alfa-2a will be administered as 180 micrograms (mcg) once weekly via subcutaneous (SC) injection.; Other Names: Pegasys ; Drug: Ribavirin; Ribavirin will be administered as 1000 to 1200 milligrams (mg) per day in divided oral doses.; Other Names: Copegus

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Alanine Aminotransferase (ALT) Normalization Plus Negative Hepatitis D Virus (HDV) Ribonucleic Acid (RNA) at 48 Weeks After End of Treatment [Week 96]

   Normalized ALT was defined as ALT value above the upper limit of normal (ULN) at Baseline with a decrease in ALT value to at/below the ULN at 48 weeks after end of treatment (Week 96). Negative HDV RNA was defined as HDV RNA not detected by polymerase chain reaction (PCR). The number of participants with ALT normalization and negative HDV RNA at Week 96 was reported.

Secondary Outcome Measures

1. Number of Participants With ALT Normalization Plus Negative HDV RNA at End of Treatment [Week 48]

   Normalized ALT was defined as ALT value above the ULN at Baseline with a decrease in ALT value to at/below the ULN at the end of treatment (Week 48). Negative HDV RNA was defined as HDV RNA not detected by PCR. The number of participants with ALT normalization and negative HDV RNA at Week 48 was reported.

2. Number of Participants With ALT Normalization at 48 Weeks After End of Treatment [Week 96]

   Normalized ALT was defined as ALT value above the ULN at Baseline with a decrease in ALT value to at/below the ULN at 48 weeks after end of treatment (Week 96). The number of participants with ALT normalization at Week 96 was reported.

3. Number of Participants With ALT Normalization at End of Treatment [Week 48]

   Normalized ALT was defined as ALT value above the ULN at Baseline with a decrease in ALT value to at/below the ULN at the end of treatment (Week 48). The number of participants with ALT normalization at Week 48 was reported.

4. Number of Participants With Negative HDV RNA at 48 Weeks After End of Treatment [Week 96]

   Negative HDV RNA was defined as HDV RNA not detected by PCR. The number of participants with negative HDV RNA at 48 weeks after end of treatment (Week 96) was reported.

5. Number of Participants With Negative HDV RNA at End of Treatment [Week 48]

   Negative HDV RNA was defined as HDV RNA not detected by PCR. The number of participants with negative HDV RNA at the end of treatment (Week 48) was reported.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Positive hepatitis B surface antigen (HBsAg) for the prior 6 months

• Positive anti-delta for the prior 3 months

• Positive HDV RNA at Screening

• Elevated ALT (1 to 10 times upper limit of normal) prior to first dose

• Chronic, necroinflammatory hepatitis documented within the prior 18 months (non-cirrhotic) or 30 months (cirrhotic)

• Negative pregnancy and adequate contraceptive use

Exclusion Criteria:

• Antiviral therapy for CHD within previous 3 months

• Positive for hepatitis A or C, or human immunodeficiency virus (HIV)

• Increased risk of metabolic liver disease

• Decompensated liver disease

• Elevated bilirubin

• Poor hematologic or renal function

• Drug/alcohol abuse within 1 year prior to study

• History of significant psychiatric, autoimmune, pulmonary, cardiac, oncologic, or thyroid disease

• Organ transplantation with existing functional graft

• Retinopathy or other ophthalmologic complication of diabetes or hypertension

• Inclusion in another investigational trial within previous 12 weeks

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Cagliari		Italy	09042

Sponsors and Collaborators

• Hoffmann-La Roche

Investigators

• Study Chair: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT02731131
• Other Study ID Numbers: ML18149
• First Posted: Apr 7, 2016
• Last Update Posted: Jul 15, 2016
• Last Verified: Jun 1, 2016

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

Study Results

Participant Flow

Arm/Group Title	Group A: Monotherapy With Peginterferon Alfa-2a	Group B: Combination With Peginterferon Alfa-2a + Ribavirin
Arm/Group Description	Participants received peginterferon alfa-2a for 48 weeks as 180 micrograms (mcg) once weekly via subcutaneous (SC) injection.	Participants received peginterferon alfa-2a plus ribavirin for 48 weeks. Peginterferon alfa-2a was given as 180 mcg once weekly via SC injection. Ribavirin was administered as 1000 to 1200 milligrams (mg) per day in divided (morning/evening) oral doses. The specific dose was determined according to the participant's body weight at Baseline.
Period Title: Overall Study
STARTED	6	6
COMPLETED	6	4
NOT COMPLETED	0	2

Baseline Characteristics

Arm/Group Title	Group A: Monotherapy With Peginterferon Alfa-2a	Group B: Combination With Peginterferon Alfa-2a + Ribavirin	Total
Arm/Group Description	Participants received peginterferon alfa-2a for 48 weeks as 180 mcg once weekly via SC injection.	Participants received peginterferon alfa-2a plus ribavirin for 48 weeks. Peginterferon alfa-2a was given as 180 mcg once weekly via SC injection. Ribavirin was administered as 1000 to 1200 mg per day in divided (morning/evening) oral doses. The specific dose was determined according to the participant's body weight at Baseline.	Total of all reporting groups
Overall Participants	6	6	12
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	47.2 (9.2)	49.2 (7.4)	48.2 (8.0)
Sex: Female, Male (Count of Participants)
Female	1 16.7%	0 0%	1 8.3%
Male	5 83.3%	6 100%	11 91.7%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Alanine Aminotransferase (ALT) Normalization Plus Negative Hepatitis D Virus (HDV) Ribonucleic Acid (RNA) at 48 Weeks After End of Treatment
Description	Normalized ALT was defined as ALT value above the upper limit of normal (ULN) at Baseline with a decrease in ALT value to at/below the ULN at 48 weeks after end of treatment (Week 96). Negative HDV RNA was defined as HDV RNA not detected by polymerase chain reaction (PCR). The number of participants with ALT normalization and negative HDV RNA at Week 96 was reported.
Time Frame	Week 96

Outcome Measure Data

Analysis Population Description

ITT Population.

Arm/Group Title	Group A: Monotherapy With Peginterferon Alfa-2a	Group B: Combination With Peginterferon Alfa-2a + Ribavirin
Arm/Group Description	Participants received peginterferon alfa-2a for 48 weeks as 180 mcg once weekly via SC injection.	Participants received peginterferon alfa-2a plus ribavirin for 48 weeks. Peginterferon alfa-2a was given as 180 mcg once weekly via SC injection. Ribavirin was administered as 1000 to 1200 mg per day in divided (morning/evening) oral doses. The specific dose was determined according to the participant's body weight at Baseline.
Measure Participants	6	6
Number [participants]	0 0%	1 16.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group A: Monotherapy With Peginterferon Alfa-2a, Group B: Combination With Peginterferon Alfa-2a + Ribavirin
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.30
	Comments
	Method	Fisher Exact
	Comments

2. Secondary Outcome

Title	Number of Participants With ALT Normalization Plus Negative HDV RNA at End of Treatment
Description	Normalized ALT was defined as ALT value above the ULN at Baseline with a decrease in ALT value to at/below the ULN at the end of treatment (Week 48). Negative HDV RNA was defined as HDV RNA not detected by PCR. The number of participants with ALT normalization and negative HDV RNA at Week 48 was reported.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

ITT Population.

Arm/Group Title	Group A: Monotherapy With Peginterferon Alfa-2a	Group B: Combination With Peginterferon Alfa-2a + Ribavirin
Arm/Group Description	Participants received peginterferon alfa-2a for 48 weeks as 180 mcg once weekly via SC injection.	Participants received peginterferon alfa-2a plus ribavirin for 48 weeks. Peginterferon alfa-2a was given as 180 mcg once weekly via SC injection. Ribavirin was administered as 1000 to 1200 mg per day in divided (morning/evening) oral doses. The specific dose was determined according to the participant's body weight at Baseline.
Measure Participants	6	6
Number [participants]	0 0%	0 0%

3. Secondary Outcome

Title	Number of Participants With ALT Normalization at 48 Weeks After End of Treatment
Description	Normalized ALT was defined as ALT value above the ULN at Baseline with a decrease in ALT value to at/below the ULN at 48 weeks after end of treatment (Week 96). The number of participants with ALT normalization at Week 96 was reported.
Time Frame	Week 96

Outcome Measure Data

Analysis Population Description

ITT Population.

Arm/Group Title	Group A: Monotherapy With Peginterferon Alfa-2a	Group B: Combination With Peginterferon Alfa-2a + Ribavirin
Arm/Group Description	Participants received peginterferon alfa-2a for 48 weeks as 180 mcg once weekly via SC injection.	Participants received peginterferon alfa-2a plus ribavirin for 48 weeks. Peginterferon alfa-2a was given as 180 mcg once weekly via SC injection. Ribavirin was administered as 1000 to 1200 mg per day in divided (morning/evening) oral doses. The specific dose was determined according to the participant's body weight at Baseline.
Measure Participants	6	6
Number [participants]	3 50%	1 16.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group A: Monotherapy With Peginterferon Alfa-2a, Group B: Combination With Peginterferon Alfa-2a + Ribavirin
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.22
	Comments
	Method	Fisher Exact
	Comments

4. Secondary Outcome

Title	Number of Participants With ALT Normalization at End of Treatment
Description	Normalized ALT was defined as ALT value above the ULN at Baseline with a decrease in ALT value to at/below the ULN at the end of treatment (Week 48). The number of participants with ALT normalization at Week 48 was reported.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

ITT Population.

Arm/Group Title	Group A: Monotherapy With Peginterferon Alfa-2a	Group B: Combination With Peginterferon Alfa-2a + Ribavirin
Arm/Group Description	Participants received peginterferon alfa-2a for 48 weeks as 180 mcg once weekly via SC injection.	Participants received peginterferon alfa-2a plus ribavirin for 48 weeks. Peginterferon alfa-2a was given as 180 mcg once weekly via SC injection. Ribavirin was administered as 1000 to 1200 mg per day in divided (morning/evening) oral doses. The specific dose was determined according to the participant's body weight at Baseline.
Measure Participants	6	6
Number [participants]	1 16.7%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group A: Monotherapy With Peginterferon Alfa-2a, Group B: Combination With Peginterferon Alfa-2a + Ribavirin
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.30
	Comments
	Method	Fisher Exact
	Comments

5. Secondary Outcome

Title	Number of Participants With Negative HDV RNA at 48 Weeks After End of Treatment
Description	Negative HDV RNA was defined as HDV RNA not detected by PCR. The number of participants with negative HDV RNA at 48 weeks after end of treatment (Week 96) was reported.
Time Frame	Week 96

Outcome Measure Data

Analysis Population Description

ITT Population.

Arm/Group Title	Group A: Monotherapy With Peginterferon Alfa-2a	Group B: Combination With Peginterferon Alfa-2a + Ribavirin
Arm/Group Description	Participants received peginterferon alfa-2a for 48 weeks as 180 mcg once weekly via SC injection.	Participants received peginterferon alfa-2a plus ribavirin for 48 weeks. Peginterferon alfa-2a was given as 180 mcg once weekly via SC injection. Ribavirin was administered as 1000 to 1200 mg per day in divided (morning/evening) oral doses. The specific dose was determined according to the participant's body weight at Baseline.
Measure Participants	6	6
Number [participants]	0 0%	1 16.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group A: Monotherapy With Peginterferon Alfa-2a, Group B: Combination With Peginterferon Alfa-2a + Ribavirin
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.30
	Comments
	Method	Fisher Exact
	Comments

6. Secondary Outcome

Title	Number of Participants With Negative HDV RNA at End of Treatment
Description	Negative HDV RNA was defined as HDV RNA not detected by PCR. The number of participants with negative HDV RNA at the end of treatment (Week 48) was reported.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

ITT Population.

Arm/Group Title	Group A: Monotherapy With Peginterferon Alfa-2a	Group B: Combination With Peginterferon Alfa-2a + Ribavirin
Arm/Group Description	Participants received peginterferon alfa-2a for 48 weeks as 180 mcg once weekly via SC injection.	Participants received peginterferon alfa-2a plus ribavirin for 48 weeks. Peginterferon alfa-2a was given as 180 mcg once weekly via SC injection. Ribavirin was administered as 1000 to 1200 mg per day in divided (morning/evening) oral doses. The specific dose was determined according to the participant's body weight at Baseline.
Measure Participants	6	6
Number [participants]	1 16.7%	2 33.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group A: Monotherapy With Peginterferon Alfa-2a, Group B: Combination With Peginterferon Alfa-2a + Ribavirin
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.50
	Comments
	Method	Fisher Exact
	Comments

Adverse Events

Time Frame	Baseline through 24 weeks after end of treatment (up to 72 weeks)
Adverse Event Reporting Description	Safety Population: All randomized participants who received at least one dose of study medication and had at least one post-baseline safety assessment.
Arm/Group Title	Group A: Monotherapy With Peginterferon Alfa-2a		Group B: Combination With Peginterferon Alfa-2a + Ribavirin
Arm/Group Description	Participants received peginterferon alfa-2a for 48 weeks as 180 mcg once weekly via SC injection.		Participants received peginterferon alfa-2a plus ribavirin for 48 weeks. Peginterferon alfa-2a was given as 180 mcg once weekly via SC injection. Ribavirin was administered as 1000 to 1200 mg per day in divided (morning/evening) oral doses. The specific dose was determined according to the participant's body weight at Baseline.
All Cause Mortality
	Group A: Monotherapy With Peginterferon Alfa-2a		Group B: Combination With Peginterferon Alfa-2a + Ribavirin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Group A: Monotherapy With Peginterferon Alfa-2a		Group B: Combination With Peginterferon Alfa-2a + Ribavirin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/6 (0%)
Other (Not Including Serious) Adverse Events
	Group A: Monotherapy With Peginterferon Alfa-2a		Group B: Combination With Peginterferon Alfa-2a + Ribavirin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/6 (100%)		6/6 (100%)
Blood and lymphatic system disorders
Neutropenia	1/6 (16.7%)		1/6 (16.7%)
Thrombocytopenia	1/6 (16.7%)		1/6 (16.7%)
Lymphadenopathy	0/6 (0%)		1/6 (16.7%)
Eye disorders
Conjunctivitis	0/6 (0%)		1/6 (16.7%)
Gastrointestinal disorders
Diarrhoea	2/6 (33.3%)		0/6 (0%)
Nausea	2/6 (33.3%)		1/6 (16.7%)
Abdominal pain	1/6 (16.7%)		2/6 (33.3%)
Dyspepsia	1/6 (16.7%)		0/6 (0%)
Dry mouth	0/6 (0%)		1/6 (16.7%)
Flatulence	0/6 (0%)		1/6 (16.7%)
Stomatitis	0/6 (0%)		1/6 (16.7%)
General disorders
Asthenia	5/6 (83.3%)		3/6 (50%)
Pyrexia	5/6 (83.3%)		3/6 (50%)
Influenza like illness	2/6 (33.3%)		1/6 (16.7%)
Malaise	1/6 (16.7%)		0/6 (0%)
Fatigue	0/6 (0%)		1/6 (16.7%)
Infections and infestations
Upper respiratory tract infection	0/6 (0%)		2/6 (33.3%)
Metabolism and nutrition disorders
Anorexia	2/6 (33.3%)		2/6 (33.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	5/6 (83.3%)		2/6 (33.3%)
Myalgia	4/6 (66.7%)		2/6 (33.3%)
Back pain	1/6 (16.7%)		0/6 (0%)
Neck pain	1/6 (16.7%)		0/6 (0%)
Musculoskeletal pain	0/6 (0%)		1/6 (16.7%)
Nervous system disorders
Headache	3/6 (50%)		2/6 (33.3%)
Dizziness	1/6 (16.7%)		0/6 (0%)
Disturbance in attention	0/6 (0%)		1/6 (16.7%)
Dysgeusia	0/6 (0%)		1/6 (16.7%)
Neuropathy peripheral	0/6 (0%)		1/6 (16.7%)
Tremor	0/6 (0%)		1/6 (16.7%)
Psychiatric disorders
Insomnia	4/6 (66.7%)		3/6 (50%)
Depression	2/6 (33.3%)		3/6 (50%)
Irritability	2/6 (33.3%)		3/6 (50%)
Emotional disorder	1/6 (16.7%)		0/6 (0%)
Nervousness	1/6 (16.7%)		1/6 (16.7%)
Anxiety	0/6 (0%)		4/6 (66.7%)
Renal and urinary disorders
Renal colic	1/6 (16.7%)		0/6 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	3/6 (50%)		2/6 (33.3%)
Epistaxis	1/6 (16.7%)		0/6 (0%)
Pharyngolaryngeal pain	0/6 (0%)		1/6 (16.7%)
Skin and subcutaneous tissue disorders
Pruritus	2/6 (33.3%)		1/6 (16.7%)
Dermatitis	1/6 (16.7%)		0/6 (0%)

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.