Alisporivir (Deb025) and Boceprevir Triple Therapies in African American Participants Not Previously Treated for Chronic Hepatitis C Genotype 1

• Sponsor: Debiopharm International SA (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01446250
• Collaborator: (none)
• Enrollment: 8
• Locations: 2
• Arms: 2
• Duration (Months): 17
• Patients Per Site: 4
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This study will assess the safety and efficacy of alisporivir (ALV) and boceprevir (BOC), each in combination with Peginterferon alfa-2a (PEG) and Ribavirin (RBV), in African American participants who have never received treatment for their chronic hepatitis C (HCV) genotype 1 infection.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis C	Drug: Alisporivir; Drug: Boceprevir; Drug: Peginterferon alfa-2a; Drug: Ribavirin	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 8 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized, Open Label Trial of the Safety and Efficacy of DEB025/Alisporivir in Combination With Pegylated Interferon-α2a and Ribavirin (Peg-INFα2a/RBV) and Boceprevir in Combination With Peg-INFα2a/RBV in African American Treatment-naïve Patients With Chronic Hepatitis C Genotype 1
• Study Start Date: Dec 1, 2011
• Actual Primary Completion Date: May 1, 2013
• Actual Study Completion Date: May 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Alisporivir At the time of partial clinical hold, participants randomized to original treatment arms A and B (Alisporivir triple therapy arms with Peginterferon alfa-2a and Ribavirin) discontinued alisporivir treatment immediately while continuing their treatments with the other two therapies. These participants were combined into the same arm because they received the same dose of alisporivir 400 mg twice per day (BID) for the same duration. Amendment 1 offered them the opportunity to continue in the study receiving boceprevir triple therapy.	Drug: Alisporivir; ALV 200 mg soft gel capsules administered orally; Other Names: DEB025 ; Drug: Peginterferon alfa-2a; PEG 180 μg administered via subcutaneous (s.c.) injection once weekly; Other Names: Pegasys® ; Drug: Ribavirin; RBV 200 mg tablets (weight-based dose: < 75 mg = 1000 mg/day; ≥ 75 kg = 1200 mg/day) administered orally in a divided daily dose; Other Names: Copegus®
Active Comparator: Boceprevir Participants randomized to boceprevir triple therapy with Peginterferon alfa-2a and Ribavirin (the original treatment arm C).	Drug: Boceprevir; BOC 800 mg (4 x 200 mg soft gel capsules) administered orally; Other Names: Victrelis® ; Drug: Peginterferon alfa-2a; PEG 180 μg administered via subcutaneous (s.c.) injection once weekly; Other Names: Pegasys® ; Drug: Ribavirin; RBV 200 mg tablets (weight-based dose: < 75 mg = 1000 mg/day; ≥ 75 kg = 1200 mg/day) administered orally in a divided daily dose; Other Names: Copegus®

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants That Discontinued Study Drug or Required Dose Reduction or Dose Interruption Due to Treatment-emergent Adverse Events [within 48 weeks]

Secondary Outcome Measures

1. Percentage of Participants With Emergence of Resistant Mutations [within 48 weeks]

2. Percentage of Participants Who Achieved Sustained Virologic Response (SVR) 24 Weeks After the End of Treatment (SVR24) [24 weeks post-treatment]

   SVR24 was defined as hepatitis C virus (HCV) RNA undetectable (by limit of detection) 24 weeks after end of treatment.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion criteria:

• Chronic HCV genotype 1 infection

• No previous treatment for HCV infection

• African American ethnicity

• Serum HCV RNA ≥ 1000 IU/ml, assessed by quantitative polymerase chain reaction or equivalent at screening visit, no upper limit

• A liver biopsy within 3 years prior to baseline

Exclusion criteria:

• HCV genotype different from genotype 1 or co-infection with other HCV genotype

• Co-infection with Hepatitis B or HIV

• Any other cause of relevant liver disease other than HCV

• Presence or history of hepatic decompensation

• Alanine aminotransferase (ALT) ≥ 10 times ULN, more than 1 episode of elevated bilirubin (> ULN) in past 6 months

Other protocol-defined inclusion/exclusion criteria may apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigational Site	Beverly Hills	California	United States	90211
2	Novartis Investigational Site	Baltimore	Maryland	United States	21229

Sponsors and Collaborators

• Debiopharm International SA

Investigators

• Study Director: Novartis Pharmaceticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Debiopharm International SA
• ClinicalTrials.gov Identifier: NCT01446250
• Other Study ID Numbers: CDEB025A2307
• First Posted: Oct 5, 2011
• Last Update Posted: Jan 16, 2017
• Last Verified: Nov 1, 2016

• Keywords provided by Debiopharm International SA: Chronic hepatitis C; Cyclophilin inhibitor
• Additional relevant MeSH terms: Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis; Hepatitis, Chronic; Ribavirin; Peginterferon alfa-2a

Study Results

Participant Flow

Arm/Group Title	Alisporivir	Boceprevir	PEGinf + RBV	No Intervention
Arm/Group Description	Participants randomized to Treatment A and B received Alisporivir (ALV) 400 mg twice daily (BID) with Peginterferon alfa-2a (PEGinf) and Ribavirin (RBV) in Treatment Period 1.	Participants randomized to Treatment C received Boceprevir (BOC) 800 mg three times daily (TID) with PEGinf and RBV in Treatment Period 1. Participants who received ALV in Treatment Period 1 and were put on clinical hold for 4 weeks, received BOC 800 mg TID with PEGinf and RBV in Treatment Period 2.	Participants who received ALV in Treatment Period 1 were put on clinical hold but continued receiving PEGinf and RBV for 4 weeks, after which they switched to BOC triple therapy in Treatment Period 2.	Participants who had an End of Treatment Response (ETR) were followed-up for 24 weeks after the last dose of BOC triple therapy (in Treatment Period 2) and participants who did not respond for any reason or discontinued the treatment early were followed-up for 12 weeks after the last dose of BOC (in Treatment Period 2).
Period Title: Treatment Period 1
STARTED	5	3	0	0
COMPLETED	5	2	0	0
NOT COMPLETED	0	1	0	0
Period Title: Treatment Period 1
STARTED	0	2	5	0
COMPLETED	0	2	5	0
NOT COMPLETED	0	0	0	0
Period Title: Treatment Period 1
STARTED	0	7	0	0
COMPLETED	0	6	0	0
NOT COMPLETED	0	1	0	0
Period Title: Treatment Period 1
STARTED	0	0	0	6
COMPLETED	0	0	0	0
NOT COMPLETED	0	0	0	6

Baseline Characteristics

Arm/Group Title	All Enrolled Participants
Arm/Group Description	Analysis was performed on all enrolled participants.
Overall Participants	8
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	8 100%
>=65 years	0 0%
Gender (Count of Participants)
Female	5 62.5%
Male	3 37.5%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants That Discontinued Study Drug or Required Dose Reduction or Dose Interruption Due to Treatment-emergent Adverse Events
Time Frame	within 48 weeks

Outcome Measure Data

Analysis Population Description

No data has been reported because planned data analyses were not performed as the study was terminated before the outcome measure time point.

Arm/Group Title	Alisporivir	Boceprevir
Arm/Group Description	Participants randomized to Treatment A and B received Alisporivir (ALV) 400 mg twice daily (BID) with Peginterferon alfa-2a (PEGinf) and Ribavirin (RBV) in Treatment Period 1.	Participants randomized to Treatment C received Boceprevir (BOC) 800 mg three times daily (TID) with PEGinf and RBV in Treatment Period 1. Participants who received ALV in Treatment Period 1 and were put on clinical hold for 4 weeks, received BOC 800 mg TID with PEGinf and RBV in Treatment Period 2.
Measure Participants	0	0

2. Secondary Outcome

Title	Percentage of Participants With Emergence of Resistant Mutations
Time Frame	within 48 weeks

Outcome Measure Data

Analysis Population Description

No data has been reported because planned data analyses were not performed as the study was terminated before the outcome measure time point.

Arm/Group Title	Alisporivir	Boceprevir
Arm/Group Description	Participants randomized to Treatment A and B received Alisporivir (ALV) 400 mg twice daily (BID) with Peginterferon alfa-2a (PEGinf) and Ribavirin (RBV) in Treatment Period 1.	Participants randomized to Treatment C received Boceprevir (BOC) 800 mg three times daily (TID) with PEGinf and RBV in Treatment Period 1. Participants who received ALV in Treatment Period 1 and were put on clinical hold for 4 weeks, received BOC 800 mg TID with PEGinf and RBV in Treatment Period 2.
Measure Participants	0	0

3. Secondary Outcome

Title	Percentage of Participants Who Achieved Sustained Virologic Response (SVR) 24 Weeks After the End of Treatment (SVR24)
Description	SVR24 was defined as hepatitis C virus (HCV) RNA undetectable (by limit of detection) 24 weeks after end of treatment.
Time Frame	24 weeks post-treatment

Outcome Measure Data

Analysis Population Description

No data has been reported because planned data analyses were not performed as the study was terminated before the outcome measure time point.

Arm/Group Title	Alisporivir	Boceprevir
Arm/Group Description	Participants randomized to Treatment A and B received Alisporivir (ALV) 400 mg twice daily (BID) with Peginterferon alfa-2a (PEGinf) and Ribavirin (RBV) in Treatment Period 1.	Participants randomized to Treatment C received Boceprevir (BOC) 800 mg three times daily (TID) with PEGinf and RBV in Treatment Period 1. Participants who received ALV in Treatment Period 1 and were put on clinical hold for 4 weeks, received BOC 800 mg TID with PEGinf and RBV in Treatment Period 2.
Measure Participants	0	0

Adverse Events

Arm/Group Title	Alisporivir		Boceprevir		PEGinf + RBV		No Intervention
Arm/Group Description	Adverse event (AE) occurred while taking Alisporivir + PEGinf + RBV.		AE occurred while taking Boceprevir + PEGinf + RBV.		AE occurred while taking only PEGinf + RBV.		AE was discovered while taking no intervention.
All Cause Mortality
	Alisporivir		Boceprevir		PEGinf + RBV		No Intervention
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Alisporivir		Boceprevir		PEGinf + RBV		No Intervention
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		1/8 (12.5%)		0/8 (0%)		0/6 (0%)
Respiratory, thoracic and mediastinal disorders
Chronic Obstructive Pulmonary Disease	0/5 (0%)		1/8 (12.5%)		0/8 (0%)		0/6 (0%)
Other (Not Including Serious) Adverse Events
	Alisporivir		Boceprevir		PEGinf + RBV		No Intervention
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/5 (100%)		8/8 (100%)		4/8 (50%)		1/6 (16.7%)
Blood and lymphatic system disorders
Anaemia	0/5 (0%)		3/8 (37.5%)		0/8 (0%)		0/6 (0%)
Neutropenia	1/5 (20%)		1/8 (12.5%)		1/8 (12.5%)		0/6 (0%)
Eye disorders
Vision Blurred	1/5 (20%)		0/8 (0%)		0/8 (0%)		0/6 (0%)
Gastrointestinal disorders
Diarrhoea	1/5 (20%)		2/8 (25%)		2/8 (25%)		0/6 (0%)
Gastric Ulcer	0/5 (0%)		0/8 (0%)		0/8 (0%)		1/6 (16.7%)
Vomiting	1/5 (20%)		0/8 (0%)		1/8 (12.5%)		0/6 (0%)
Nausea	1/5 (20%)		1/8 (12.5%)		2/8 (25%)		0/6 (0%)
Dry Mouth	0/5 (0%)		0/8 (0%)		2/8 (25%)		0/6 (0%)
Abdominal Pain Upper	0/5 (0%)		0/8 (0%)		1/8 (12.5%)		0/6 (0%)
General disorders
Fatigue	1/5 (20%)		2/8 (25%)		3/8 (37.5%)		0/6 (0%)
Influenza Like Illness	1/5 (20%)		0/8 (0%)		0/8 (0%)		0/6 (0%)
Pyrexia	1/5 (20%)		0/8 (0%)		1/8 (12.5%)		0/6 (0%)
Chest Discomfort	0/5 (0%)		1/8 (12.5%)		0/8 (0%)		0/6 (0%)
Pain	1/5 (20%)		1/8 (12.5%)		1/8 (12.5%)		0/6 (0%)
Injection Site Erythema	0/5 (0%)		0/8 (0%)		1/8 (12.5%)		0/6 (0%)
Non-Cardiac Chest Pain	0/5 (0%)		0/8 (0%)		1/8 (12.5%)		0/6 (0%)
Irritability	0/5 (0%)		0/8 (0%)		1/8 (12.5%)		0/6 (0%)
Immune system disorders
Seasonal Allergy	0/5 (0%)		0/8 (0%)		1/8 (12.5%)		0/6 (0%)
Infections and infestations
Nasopharyngitis	0/5 (0%)		1/8 (12.5%)		0/8 (0%)		0/6 (0%)
Gastroenteritis Viral	0/5 (0%)		1/8 (12.5%)		0/8 (0%)		0/6 (0%)
Pharyngitis Streptococcal	0/5 (0%)		1/8 (12.5%)		0/8 (0%)		0/6 (0%)
Oral Candidiasis	0/5 (0%)		1/8 (12.5%)		0/8 (0%)		0/6 (0%)
Investigations
Haematocrit Decreased	1/5 (20%)		1/8 (12.5%)		0/8 (0%)		0/6 (0%)
Haemoglobin Decreased	1/5 (20%)		1/8 (12.5%)		0/8 (0%)		0/6 (0%)
Blood Creatinine Increased	0/5 (0%)		0/8 (0%)		1/8 (12.5%)		0/6 (0%)
Metabolism and nutrition disorders
Decreased Appetite	1/5 (20%)		0/8 (0%)		1/8 (12.5%)		0/6 (0%)
Hypertriglyceridaemia	1/5 (20%)		0/8 (0%)		0/8 (0%)		0/6 (0%)
Gout	0/5 (0%)		0/8 (0%)		1/8 (12.5%)		0/6 (0%)
Nervous system disorders
Headache	2/5 (40%)		2/8 (25%)		1/8 (12.5%)		0/6 (0%)
Disturbance in Attention	1/5 (20%)		0/8 (0%)		0/8 (0%)		0/6 (0%)
Dysgeusia	0/5 (0%)		1/8 (12.5%)		1/8 (12.5%)		0/6 (0%)
Dizziness	0/5 (0%)		1/8 (12.5%)		2/8 (25%)		0/6 (0%)
Ageusia	0/5 (0%)		0/8 (0%)		1/8 (12.5%)		0/6 (0%)
Memory Impairment	0/5 (0%)		0/8 (0%)		1/8 (12.5%)		0/6 (0%)
Psychiatric disorders
Sleep Disorder	0/5 (0%)		0/8 (0%)		2/8 (25%)		0/6 (0%)
Libido Decreased	0/5 (0%)		0/8 (0%)		2/8 (25%)		0/6 (0%)
Confusional State	0/5 (0%)		0/8 (0%)		1/8 (12.5%)		0/6 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	0/5 (0%)		0/8 (0%)		2/8 (25%)		0/6 (0%)
Dyspnoea	0/5 (0%)		0/8 (0%)		1/8 (12.5%)		0/6 (0%)
Skin and subcutaneous tissue disorders
Pruritus Generalised	1/5 (20%)		0/8 (0%)		0/8 (0%)		0/6 (0%)
Rash Pruritic	2/5 (40%)		0/8 (0%)		0/8 (0%)		0/6 (0%)
Rash	0/5 (0%)		1/8 (12.5%)		1/8 (12.5%)		0/6 (0%)
Vascular disorders
Hot Flush	0/5 (0%)		0/8 (0%)		1/8 (12.5%)		0/6 (0%)

Limitations/Caveats

Due to the early termination of study enrollment and discontinuation of alisporivir treatment, Amendment 1 changed the number of study arms to 2, combining Arms A and B, and none of the planned outcome measures could be evaluated.

More Information

Certain Agreements

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