Trial Outcomes & Findings for Phase III China GT 1b Interferon (IFN) Intolerant Prev Exclude Dual (NCT NCT01995266)

NCT ID: NCT01995266

Last Updated: 2020-08-11

Results Overview

SVR was defined as Hepatitis C Virus ribonucleic acid (HCV RNA) \< lower limit of quantitation (LLOQ) target detected (TD) or not detected (TND) at post-treatment follow-up Week 24.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 218 participants
• Primary outcome timeframe: 24 Weeks after treatment discontinuation (Follow-up Week 24)
• Results posted on: 2020-08-11

Participant Flow

Of 218 participants enrolled, 159 were treated. Of the 59 who were not treated, 55 did not meet study criteria and 4 withdrew consent to participate.

Participant milestones

Measure	All Subjects Oral dose of daclatasvir (DCV) 60 mg once daily (QD) and asunaprevir (ASV) 100 mg twice daily (BID) was administered for 24 weeks. Thereafter, participants entered a follow-up period of 24 weeks after completion of study treatment or upon early discontinuation of treatment.
Overall Study STARTED	159
Overall Study COMPLETED	150
Overall Study NOT COMPLETED	9

Reasons for withdrawal

Measure	All Subjects Oral dose of daclatasvir (DCV) 60 mg once daily (QD) and asunaprevir (ASV) 100 mg twice daily (BID) was administered for 24 weeks. Thereafter, participants entered a follow-up period of 24 weeks after completion of study treatment or upon early discontinuation of treatment.
Overall Study Death	1
Overall Study Lack of Efficacy	6
Overall Study Adverse Event	2

Baseline Characteristics

Phase III China GT 1b Interferon (IFN) Intolerant Prev Exclude Dual

Baseline characteristics by cohort

Measure	All Subjects n=159 Participants Oral dose of daclatasvir (DCV) 60 mg once daily (QD) and asunaprevir (ASV) 100 mg twice daily (BID) was administered for 24 weeks. Thereafter, participants entered a follow-up period of 24 weeks after completion of study treatment or upon early discontinuation of treatment.
Age, Continuous	53.6 years STANDARD_DEVIATION 12.30 • n=5 Participants
Sex: Female, Male Female	104 Participants n=5 Participants
Sex: Female, Male Male	55 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	159 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: 24 Weeks after treatment discontinuation (Follow-up Week 24)

Population: All treated and evaluable participants.

SVR was defined as Hepatitis C Virus ribonucleic acid (HCV RNA) < lower limit of quantitation (LLOQ) target detected (TD) or not detected (TND) at post-treatment follow-up Week 24.

Outcome measures

Measure	All Subjects n=159 Participants Oral dose of daclatasvir (DCV) 60 mg once daily (QD) and asunaprevir (ASV) 100 mg twice daily (BID) was administered for 24 weeks. Thereafter, participants entered a follow-up period of 24 weeks after completion of study treatment or upon early discontinuation of treatment.
Percentage of Participants With Sustained Virologic Response (SVR) at Post-Treatment Follow-up Week 24 (SVR24)	91.2 Percentage of participants Interval 85.7 to 95.1

SECONDARY outcome

Timeframe: 12 Weeks after treatment discontinuation (Follow-up Week 12)

Population: All treated and evaluable participants.

SVR12 was defined as HCV RNA < LLOQ target detected or not detected at post-treatment follow-up Week 12. For SVR12, missing HCV RNA data at follow-up Week 12 was imputed using the Next Value Carried Backwards (NVCB) approach.

Outcome measures

Measure	All Subjects n=159 Participants Oral dose of daclatasvir (DCV) 60 mg once daily (QD) and asunaprevir (ASV) 100 mg twice daily (BID) was administered for 24 weeks. Thereafter, participants entered a follow-up period of 24 weeks after completion of study treatment or upon early discontinuation of treatment.
Percentage of Participants With Sustained Virologic Response (SVR) at Post-Treatment Follow-up Week 12 (SVR12)	91.2 Percentage of participants Interval 85.7 to 95.1

SECONDARY outcome

Timeframe: 7 days after treatment discontinuation

Population: All treated and evaluable participants.

An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death, initial or prolonged inpatient hospitalization, life-threatening experience (immediate risk of dying), persistent or significant disability/incapacity, or a congenital anomaly, or a medically important event.

Outcome measures

Measure	All Subjects n=159 Participants Oral dose of daclatasvir (DCV) 60 mg once daily (QD) and asunaprevir (ASV) 100 mg twice daily (BID) was administered for 24 weeks. Thereafter, participants entered a follow-up period of 24 weeks after completion of study treatment or upon early discontinuation of treatment.
Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Death, and AEs Leading to Discontinuation AEs leading to discontinuation	2 Participants
Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Death, and AEs Leading to Discontinuation Death	1 Participants
Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Death, and AEs Leading to Discontinuation SAEs	5 Participants
Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Death, and AEs Leading to Discontinuation AEs	118 Participants

SECONDARY outcome

Timeframe: 24 Weeks after treatment discontinuation (Follow-up Week 24)

Population: All evaluable participants of each Genotype who received treatment

Participants categorized into three genotypes based on SNPs in the IL28B gene were assessed for SVR24, defined as response in which hepatitis C virus RNA levels below lower limit of quantitation or below target detected or target not detected at follow-up Week 24.

Outcome measures

Measure	All Subjects n=159 Participants Oral dose of daclatasvir (DCV) 60 mg once daily (QD) and asunaprevir (ASV) 100 mg twice daily (BID) was administered for 24 weeks. Thereafter, participants entered a follow-up period of 24 weeks after completion of study treatment or upon early discontinuation of treatment.
Percentage of Participants With SVR24 by the rs12979860 Single Nucleotide Polymorphisms (SNP) in the IL 28B Gene at Post-Treatment Follow-up Week 24 CC Genotype	89.5 Percentage of participants
Percentage of Participants With SVR24 by the rs12979860 Single Nucleotide Polymorphisms (SNP) in the IL 28B Gene at Post-Treatment Follow-up Week 24 CT Genotype	93.0 Percentage of participants
Percentage of Participants With SVR24 by the rs12979860 Single Nucleotide Polymorphisms (SNP) in the IL 28B Gene at Post-Treatment Follow-up Week 24 TT Genotype	100 Percentage of participants

SECONDARY outcome

Timeframe: Week 24 (End-of Treatment)

Population: All treated and evaluable participants.

Blood was drawn from each participant to assess HCV RNA plasma levels using the Roche COBAS® Taqman quantitative RT-PCR assay, v2.0. The lower and upper limits of quantitation (LOQs) of the assay for HCV GT-1 were 25 IU/mL and 3.91 X10^8 IU/mL, respectively; the limit of detection was ~ 10 IU/mL

Outcome measures

Measure	All Subjects n=159 Participants Oral dose of daclatasvir (DCV) 60 mg once daily (QD) and asunaprevir (ASV) 100 mg twice daily (BID) was administered for 24 weeks. Thereafter, participants entered a follow-up period of 24 weeks after completion of study treatment or upon early discontinuation of treatment.
Percentage of Participants With HCV RNA< LLOQ Target Not Detected at the End of Treatment (Week 24)	92.5 Percentage of participants Interval 87.2 to 96.0

SECONDARY outcome

Timeframe: Treatment Week 4

Population: All treated and evaluable participants.

RVR was defined as HCV RNA < LLOQ, target not detected at treatment Week 4.

Outcome measures

Measure	All Subjects n=159 Participants Oral dose of daclatasvir (DCV) 60 mg once daily (QD) and asunaprevir (ASV) 100 mg twice daily (BID) was administered for 24 weeks. Thereafter, participants entered a follow-up period of 24 weeks after completion of study treatment or upon early discontinuation of treatment.
Number of Participants With Rapid Virologic Response (RVR)	136 Participants

SECONDARY outcome

Timeframe: Treatment Week 12

Population: All treated and evaluable participants.

cEVR was defined as HCV RNA < LLOQ, target not detected at treatment Week 12.

Outcome measures

Measure	All Subjects n=159 Participants Oral dose of daclatasvir (DCV) 60 mg once daily (QD) and asunaprevir (ASV) 100 mg twice daily (BID) was administered for 24 weeks. Thereafter, participants entered a follow-up period of 24 weeks after completion of study treatment or upon early discontinuation of treatment.
Percentage of Participants With Complete Early Virologic Response (cEVR)	96.2 Percentage of participants Interval 92.0 to 98.6

SECONDARY outcome

Timeframe: Treatment Week 4 and Week 12

Population: All treated and evaluable participants.

eRVR was defined as HCV RNA < LLOQ, target not detected at treatment Weeks 4 and 12.

Outcome measures

Measure	All Subjects n=159 Participants Oral dose of daclatasvir (DCV) 60 mg once daily (QD) and asunaprevir (ASV) 100 mg twice daily (BID) was administered for 24 weeks. Thereafter, participants entered a follow-up period of 24 weeks after completion of study treatment or upon early discontinuation of treatment.
Number of Participants With Extended Rapid Virologic Response (eRVR)	134 Participants

SECONDARY outcome

Timeframe: Week 24 (End-of Treatment)

Population: All treated and evaluable participants.

Antiviral efficacy is measured by the number of participants with HCV RNA< LLOQ (lower limit of quantification), TD (target detected) or TND (target not detected) at End of Treatment (Week 24)

Outcome measures

Measure	All Subjects n=159 Participants Oral dose of daclatasvir (DCV) 60 mg once daily (QD) and asunaprevir (ASV) 100 mg twice daily (BID) was administered for 24 weeks. Thereafter, participants entered a follow-up period of 24 weeks after completion of study treatment or upon early discontinuation of treatment.
Number of Participants With HCV RNA < LLOQ Target Detected or Not Detected at the End of Treatment (Week 24)	149 Participants

SECONDARY outcome

Timeframe: Treatment Week 4 and 12

Population: All treated and evaluable participants.

VR was defined as HCV RNA < LLOQ, target detected or not detected at specific time points (Week 4 and Week 12)

Outcome measures

Measure	All Subjects n=159 Participants Oral dose of daclatasvir (DCV) 60 mg once daily (QD) and asunaprevir (ASV) 100 mg twice daily (BID) was administered for 24 weeks. Thereafter, participants entered a follow-up period of 24 weeks after completion of study treatment or upon early discontinuation of treatment.
Number of Participants With Virologic Response (VR) at Treatment Week 4 and 12	151 Participants

Adverse Events

All Subjects

Serious events: 5 serious events

Other events: 66 other events

Deaths: 1 deaths

Serious adverse events

Measure	All Subjects n=159 participants at risk Oral dose of daclatasvir (DCV) 60 mg once daily (QD) and asunaprevir (ASV) 100 mg twice daily (BID) was administered for 24 weeks. Thereafter, participants entered a follow-up period of 24 weeks after completion of study treatment or upon early discontinuation of treatment.
Cardiac disorders Adam-Stokes Syndrome	0.63% 1/159 • Up to 24 weeks within 30 days of discontinuation of dosing Analysis was performed on all treated participants.
Cardiac disorders Asteriosclerosis Coronary Artery	0.63% 1/159 • Up to 24 weeks within 30 days of discontinuation of dosing Analysis was performed on all treated participants.
Cardiac disorders Coronary Artery Disease	0.63% 1/159 • Up to 24 weeks within 30 days of discontinuation of dosing Analysis was performed on all treated participants.
Ear and labyrinth disorders Sudden Hearing Loss	0.63% 1/159 • Up to 24 weeks within 30 days of discontinuation of dosing Analysis was performed on all treated participants.
Infections and infestations Pneumonia	0.63% 1/159 • Up to 24 weeks within 30 days of discontinuation of dosing Analysis was performed on all treated participants.
Injury, poisoning and procedural complications Femoral Neck Fracture	0.63% 1/159 • Up to 24 weeks within 30 days of discontinuation of dosing Analysis was performed on all treated participants.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatocellular Carcinoma	0.63% 1/159 • Up to 24 weeks within 30 days of discontinuation of dosing Analysis was performed on all treated participants.
Cardiac disorders Arrhythmia	0.63% 1/159 • Up to 24 weeks within 30 days of discontinuation of dosing Analysis was performed on all treated participants.

Other adverse events

Measure	All Subjects n=159 participants at risk Oral dose of daclatasvir (DCV) 60 mg once daily (QD) and asunaprevir (ASV) 100 mg twice daily (BID) was administered for 24 weeks. Thereafter, participants entered a follow-up period of 24 weeks after completion of study treatment or upon early discontinuation of treatment.
Investigations Platelet Count Decreased	8.8% 14/159 • Up to 24 weeks within 30 days of discontinuation of dosing Analysis was performed on all treated participants.
Investigations Alanine Aminotransferase Increased	6.9% 11/159 • Up to 24 weeks within 30 days of discontinuation of dosing Analysis was performed on all treated participants.
Investigations Neutrophil Count Decreased	6.9% 11/159 • Up to 24 weeks within 30 days of discontinuation of dosing Analysis was performed on all treated participants.
Investigations Monocyte Count Decreased	6.3% 10/159 • Up to 24 weeks within 30 days of discontinuation of dosing Analysis was performed on all treated participants.
Investigations White Blood Cell Count Decreased	6.3% 10/159 • Up to 24 weeks within 30 days of discontinuation of dosing Analysis was performed on all treated participants.
Investigations Aspartate Aminotransferase Increased	5.0% 8/159 • Up to 24 weeks within 30 days of discontinuation of dosing Analysis was performed on all treated participants.
Infections and infestations Upper Respiratory Tract Infection	8.2% 13/159 • Up to 24 weeks within 30 days of discontinuation of dosing Analysis was performed on all treated participants.
Blood and lymphatic system disorders Thrombocytopenia	6.3% 10/159 • Up to 24 weeks within 30 days of discontinuation of dosing Analysis was performed on all treated participants.
Skin and subcutaneous tissue disorders Pruritus	5.7% 9/159 • Up to 24 weeks within 30 days of discontinuation of dosing Analysis was performed on all treated participants.
Gastrointestinal disorders Diarrhoea	5.0% 8/159 • Up to 24 weeks within 30 days of discontinuation of dosing Analysis was performed on all treated participants.
Metabolism and nutrition disorders Hyperuricaemia	5.0% 8/159 • Up to 24 weeks within 30 days of discontinuation of dosing Analysis was performed on all treated participants.

Additional Information

Bristol-Myers Squibb Study Director

Bristol-Myers Squibb

Phone: Please email

Email: clinical.trials@bms.com

Results disclosure agreements

• Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submitting for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
• Publication restrictions are in place

Restriction type: OTHER