Alisporivir With RBV in Chronic Hepatitis C Genotype 2 and 3 Participants for Whom Interferon is Not an Option

• Sponsor: Debiopharm International SA (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02094443
• Collaborator: (none)
• Enrollment: 52
• Locations: 16
• Arms: 2
• Duration (Months): 13
• Patients Per Site: 3.3
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The primary purpose of this study is to evaluate the pharmacodynamic (i.e. hepatitis C virus (HCV) viral load), pharmacokinetic and safety profiles between two treatment groups receiving different doses of DEB025 in combination with ribavirin (RBV) during the first 12 weeks treatment in chronic hepatitis C genotype (GT)-2 and GT-3 patients who had previously failed interferon therapy or were intolerant or unable to take interferon.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis C; Liver Disease	Drug: Alisporivir; Drug: Ribavirin	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 52 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Open-label, Randomized, 2-arm, Phase II Trial of Pharmacodynamics, Pharmacokinetics and Safety of Two Dose Regimens of DEB025/Alisporivir in Combination With Ribavirin Therapy in Chronic Hepatitis C Genotype 2 and 3 Patients Who Have Previously Failed Interferon Therapy or Are Intolerant or Unable to Take Interferon.
• Study Start Date: Mar 1, 2014
• Actual Primary Completion Date: Apr 1, 2015
• Actual Study Completion Date: Apr 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Alisporivir 300 mg BID Alisporivir (ALV) 300 mg twice daily (BID) with ribavirin for 12 or 24 weeks based on Week 2 response, with a safety follow-up of at least 4 weeks, during which patients did not receive any study medication	Drug: Alisporivir; ALV 100 and 200 mg soft gel capsules administered orally; Other Names: DEB025 ; 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®
Experimental: Alisporivir 400 mg BID ALV 400 mg twice daily (BID) with ribavirin for 12 or 24 weeks based on Week 2 response, with a safety follow-up of at least 4 weeks, during which patients did not receive any study medication	Drug: Alisporivir; ALV 100 and 200 mg soft gel capsules administered orally; Other Names: DEB025 ; 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. Change From Baseline in Hepatitis C Virus Ribonucleic Acid Viral Load at Week 12 [Baseline, Week 12]

   The change in log transformed Hepatitis-C Virus (HCV) Ribonucleic acid (RNA) from baseline to Week 12.

2. Change From Baseline in Alanine Aminotransferase (ALT) at Week 12 [Baseline, Week 12]

   ALT levels were assessed as part of clinical chemistry assessments throughout the study as a measure of biochemical liver recovery. A negative change from baseline indicates less liver damage.

Secondary Outcome Measures

1. Percentage of Participants Achieving Sustained Virologic Response (SVR) 4, 12, and 24 Weeks After Treatment [Up to 24 weeks posttreatment]

   SVR is defined as HCV RNA less than the lower limit of quantification (LLOQ), i.e., <15 IU/mL, at 4 weeks (SVR4), 12 weeks (SVR12), and 24 weeks (SVR24) after treatment, respectively.

2. Percentage of Participants With Extended Rapid Virologic Response [2 weeks]

   Extended rapid virologic response (eRVR) was defined as serum HCV RNA < LLOQ after 2 weeks of treatment

3. Percentage of Participants With Rapid Virologic Response (RVR) [4 weeks]

   eRVR was defined as serum HCV RNA < LLOQ after 4 weeks of treatment

4. Percentage of Participants With End of Treatment Response (ETR) [Up to 24 weeks]

   ETR was defined as serum HCV RNA < LLOQ at treatment end (completed or prematurely discontinued).

5. Percentage of Participants With Abnormal Alanine Aminotransferase (ALT) at Baseline Who Had Normalized ALT at Treatment End and Study End [Up to 24 weeks]

   ALT is an enzyme found mostly in the cells of the liver and kidney. When the liver is damaged, ALT is released into the blood. This makes ALT a common test for liver damage, because higher ALT levels may indicate more liver damage. ALT upper limit of normal is commonly considered to be 40 international units per liter (IU/L), so abnormal ALT is above 40 IU/L.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Written informed consent must be obtained before any assessment is performed

2. Participants with HCV genotype 2 or 3 infection who have previously failed interferon therapy or are intolerant or unable to take interferon

3. Males or females aged ≥18 years

4. Diagnosed Chronic hepatitis C virus infection

Exclusion criteria:

1. Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of that medication before enrollment

2. History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes

3. Hepatitis B surface antigen (HBsAg) positive

4. Human immunodeficiency virus (HIV) positive

Other protocol-defined inclusion/exclusion criteria apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Bakersfield	California	United States	93301
2	Novartis Investigative Site	Lancaster	California	United States	93534
3	Novartis Investigative Site	San Diego	California	United States	92114
4	Novartis Investigative Site	San Diego	California	United States	92128
5	Novartis Investigative Site	St. Louis	Missouri	United States	63110
6	Novartis Investigative Site	Arlington	Texas	United States	76012
7	Novartis Investigative Site	Houston	Texas	United States	77030
8	Novartis Investigative Site	San Antonio	Texas	United States	78215
9	Novartis Investigative Site	Newport News	Virginia	United States	23602
10	Novartis Investigative Site	Seattle	Washington	United States	98101
11	Novartis Investigative Site	Seattle	Washington	United States	98104
12	Novartis Investigative Site	Clichy		France	92110
13	Novartis Investigative Site	Creteil		France	94010
14	Novartis Investigative Site	Lyon Cedex 04		France	69317
15	Novartis Investigative Site	Nice Cedex 3		France	06202
16	Novartis Investigative Site	Paris		France	75014

Sponsors and Collaborators

• Debiopharm International SA

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Debiopharm International SA
• ClinicalTrials.gov Identifier: NCT02094443
• Other Study ID Numbers: CDEB025A2233; 2013-003751-38
• First Posted: Mar 21, 2014
• Last Update Posted: Oct 13, 2016
• Last Verified: Aug 1, 2016

• Keywords provided by Debiopharm International SA: Chronic hepatitis C genotype 2; Chronic hepatitis C genotype 3; Cyclophilin inhibitor; Interferon intolerant
• Additional relevant MeSH terms: Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis; Hepatitis, Chronic; Liver Diseases; Ribavirin

Study Results

Participant Flow

Arm/Group Title	Alisporivir 300 mg BID	Alisporivir 400 mg BID
Arm/Group Description	Alisporivir (ALV) 300 mg twice per day (BID) with ribavirin (RBV) for up to 24 weeks.	ALV 400 mg BID with RBV for up to 24 weeks.
Period Title: Overall Study
STARTED	26	26
Completed at Week 12	0	1
Completed at Week 24	11	8
COMPLETED	11	9
NOT COMPLETED	15	17

Baseline Characteristics

Arm/Group Title	Alisporivir 300 mg BID	Alisporivir 400 mg BID	Total
Arm/Group Description	ALV 300 mg BID with RBV for up to 24 weeks.	ALV 400 mg BID with RBV for up to 24 weeks.	Total of all reporting groups
Overall Participants	26	26	52
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	53.4 (8.25)	54.5 (7.62)	53.9 (7.88)
Sex: Female, Male (Count of Participants)
Female	8 30.8%	12 46.2%	20 38.5%
Male	18 69.2%	14 53.8%	32 61.5%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Hepatitis C Virus Ribonucleic Acid Viral Load at Week 12
Description	The change in log transformed Hepatitis-C Virus (HCV) Ribonucleic acid (RNA) from baseline to Week 12.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	Alisporivir 300 mg BID	Alisporivir 400 mg BID
Arm/Group Description	ALV 300 mg BID with RBV for up to 24 weeks.	ALV 400 mg BID with RBV for up to 24 weeks.
Measure Participants	26	26
Baseline	6.323 (0.4785)	6.343 (0.6396)
Change from baseline	-3.935 (2.3361)	-3.855 (2.7506)

2. Primary Outcome

Title	Change From Baseline in Alanine Aminotransferase (ALT) at Week 12
Description	ALT levels were assessed as part of clinical chemistry assessments throughout the study as a measure of biochemical liver recovery. A negative change from baseline indicates less liver damage.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Participants in the safety set with available data at the given time point

Arm/Group Title	Alisporivir 300 mg BID	Alisporivir 400 mg BID
Arm/Group Description	ALV 300 mg BID with RBV for up to 24 weeks.	ALV 400 mg BID with RBV for up to 24 weeks.
Measure Participants	21	19
Baseline	77.3 (48.57)	67.9 (42.94)
Change from baseline	-67.4 (45.99)	-58.2 (44.50)

3. Secondary Outcome

Title	Percentage of Participants Achieving Sustained Virologic Response (SVR) 4, 12, and 24 Weeks After Treatment
Description	SVR is defined as HCV RNA less than the lower limit of quantification (LLOQ), i.e., <15 IU/mL, at 4 weeks (SVR4), 12 weeks (SVR12), and 24 weeks (SVR24) after treatment, respectively.
Time Frame	Up to 24 weeks posttreatment

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	Alisporivir 300 mg BID	Alisporivir 400 mg BID
Arm/Group Description	ALV 300 mg BID with RBV for up to 24 weeks.	ALV 400 mg BID with RBV for up to 24 weeks.
Measure Participants	26	26
SVR4	30.8 118.5%	38.5 148.1%
SVR12	19.2 73.8%	26.9 103.5%
SVR24	19.2 73.8%	26.9 103.5%

4. Secondary Outcome

Title	Percentage of Participants With Extended Rapid Virologic Response
Description	Extended rapid virologic response (eRVR) was defined as serum HCV RNA < LLOQ after 2 weeks of treatment
Time Frame	2 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	Alisporivir 300 mg BID	Alisporivir 400 mg BID
Arm/Group Description	ALV 300 mg BID with RBV for up to 24 weeks.	ALV 400 mg BID with RBV for up to 24 weeks.
Measure Participants	26	26
Number [percentage of participants]	0.0 0%	3.8 14.6%

5. Secondary Outcome

Title	Percentage of Participants With Rapid Virologic Response (RVR)
Description	eRVR was defined as serum HCV RNA < LLOQ after 4 weeks of treatment
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	Alisporivir 300 mg BID	Alisporivir 400 mg BID
Arm/Group Description	ALV 300 mg BID with RBV for up to 24 weeks.	ALV 400 mg BID with RBV for up to 24 weeks.
Measure Participants	26	26
Number [percentage of participants]	3.8 14.6%	15.4 59.2%

6. Secondary Outcome

Title	Percentage of Participants With End of Treatment Response (ETR)
Description	ETR was defined as serum HCV RNA < LLOQ at treatment end (completed or prematurely discontinued).
Time Frame	Up to 24 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	Alisporivir 300 mg BID	Alisporivir 400 mg BID
Arm/Group Description	ALV 300 mg BID with RBV for up to 24 weeks.	ALV 400 mg BID with RBV for up to 24 weeks.
Measure Participants	26	26
Number [percentage of participants]	46.2 177.7%	50.0 192.3%

7. Secondary Outcome

Title	Percentage of Participants With Abnormal Alanine Aminotransferase (ALT) at Baseline Who Had Normalized ALT at Treatment End and Study End
Description	ALT is an enzyme found mostly in the cells of the liver and kidney. When the liver is damaged, ALT is released into the blood. This makes ALT a common test for liver damage, because higher ALT levels may indicate more liver damage. ALT upper limit of normal is commonly considered to be 40 international units per liter (IU/L), so abnormal ALT is above 40 IU/L.
Time Frame	Up to 24 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	Alisporivir 300 mg BID	Alisporivir 400 mg BID
Arm/Group Description	ALV 300 mg BID with RBV for up to 24 weeks.	ALV 400 mg BID with RBV for up to 24 weeks.
Measure Participants	26	26
End of Treatment	73.1 281.2%	61.5 236.5%
End of Study	38.5 148.1%	42.3 162.7%

Adverse Events

Time Frame	Adverse events were collected from first subject first visit until last subject last visit. All reported serious adverse events occurred during treatment.
Adverse Event Reporting Description	The mean exposure to alisporivir and ribavirin or to their combination regimen was 17 weeks for the 300 mg arm and 15 weeks for the 400 mg arm.
Arm/Group Title	Alisporivir 300 mg BID		Alisporivir 400 mg BID
Arm/Group Description	ALV 300 mg BID with RBV for up to 24 weeks.		ALV 400 mg BID with RBV for up to 24 weeks.
All Cause Mortality
	Alisporivir 300 mg BID		Alisporivir 400 mg BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Alisporivir 300 mg BID		Alisporivir 400 mg BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/26 (11.5%)		3/26 (11.5%)
Cardiac disorders
Coronary artery disease	0/26 (0%)		1/26 (3.8%)
General disorders
General physical health deterioration	1/26 (3.8%)		0/26 (0%)
Infections and infestations
Epiglottitis	1/26 (3.8%)		0/26 (0%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	0/26 (0%)		1/26 (3.8%)
Pleural effusion	1/26 (3.8%)		0/26 (0%)
Vascular disorders
Hypertension	0/26 (0%)		1/26 (3.8%)
Other (Not Including Serious) Adverse Events
	Alisporivir 300 mg BID		Alisporivir 400 mg BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	22/26 (84.6%)		24/26 (92.3%)
Blood and lymphatic system disorders
Anaemia	5/26 (19.2%)		7/26 (26.9%)
Eye disorders
Ocular icterus	2/26 (7.7%)		1/26 (3.8%)
Dry eye	2/26 (7.7%)		2/26 (7.7%)
Gastrointestinal disorders
Abdominal pain	0/26 (0%)		2/26 (7.7%)
Abdominal pain upper	0/26 (0%)		2/26 (7.7%)
Constipation	3/26 (11.5%)		1/26 (3.8%)
Diarrhoea	2/26 (7.7%)		4/26 (15.4%)
Dry mouth	2/26 (7.7%)		1/26 (3.8%)
Gastrooesophageal reflux disease	0/26 (0%)		2/26 (7.7%)
Nausea	4/26 (15.4%)		4/26 (15.4%)
Vomiting	2/26 (7.7%)		3/26 (11.5%)
General disorders
Fatigue	6/26 (23.1%)		6/26 (23.1%)
Asthenia	5/26 (19.2%)		12/26 (46.2%)
Infections and infestations
Bronchitis	2/26 (7.7%)		1/26 (3.8%)
Nasopharyngitis	2/26 (7.7%)		0/26 (0%)
Urinary tract infection	3/26 (11.5%)		1/26 (3.8%)
Metabolism and nutrition disorders
Hypertriglyceridaemia	2/26 (7.7%)		1/26 (3.8%)
Musculoskeletal and connective tissue disorders
Muscle spasms	2/26 (7.7%)		3/26 (11.5%)
Nervous system disorders
Dizziness	0/26 (0%)		3/26 (11.5%)
Headache	4/26 (15.4%)		7/26 (26.9%)
Syncope	2/26 (7.7%)		2/26 (7.7%)
Psychiatric disorders
Anxiety	1/26 (3.8%)		4/26 (15.4%)
Depression	1/26 (3.8%)		3/26 (11.5%)
Irritability	3/26 (11.5%)		2/26 (7.7%)
Insomnia	4/26 (15.4%)		4/26 (15.4%)
Renal and urinary disorders
Dysuria	0/26 (0%)		2/26 (7.7%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	5/26 (19.2%)		6/26 (23.1%)
Productive cough	2/26 (7.7%)		0/26 (0%)
Oropharyngeal pain	0/26 (0%)		2/26 (7.7%)
Skin and subcutaneous tissue disorders
Dry skin	1/26 (3.8%)		2/26 (7.7%)
Pruritis generalised	1/26 (3.8%)		2/26 (7.7%)
Pruritis	5/26 (19.2%)		4/26 (15.4%)
Rash	3/26 (11.5%)		3/26 (11.5%)
Vascular disorders
Hypertension	4/26 (15.4%)		5/26 (19.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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