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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01581203




Registration number
NCT01581203
Ethics application status
Date submitted
18/04/2012
Date registered
20/04/2012
Date last updated
9/10/2015

Titles & IDs
Public title
Phase III Hallmark DUAL: ASV+DCV (Nulls/Partials, Intolerants/Ineligibles. Naives)
Scientific title
A Phase 3 Study With Asunaprevir and Daclatasvir (DUAL) for Null or Partial Responders to Peginterferon Alfa and Ribavirin (P/R), Intolerant or Ineligible to P/R Subjects and Treatment-Naive Subjects With Chronic Hepatitis C Genotype 1b Infection
Secondary ID [1] 0 0
2011-005446-35
Secondary ID [2] 0 0
AI447-028
Universal Trial Number (UTN)
Trial acronym
Hallmark DUAL
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hepatitis C Virus 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Asunaprevir (ASV)
Treatment: Drugs - Daclatasvir (DCV)
Treatment: Drugs - Pegylated-interferon alfa 2a (PegIFN)
Treatment: Drugs - Ribavirin (RBV)

Experimental: Arm 1: Null or Partial Responder to P/R (ASV + DCV) - Asunaprevir 100 mg Capsules by mouth, Twice daily for 24 Weeks
Daclatasvir 60 mg Tablet by mouth, Once daily for 24 Weeks

Experimental: Arm 2: Intolerant to or Ineligible for P/R (ASV + DCV) - Asunaprevir 100 mg Capsules by mouth, Twice daily for 24 Weeks
Daclatasvir 60 mg Tablet by mouth, Once daily for 24 Weeks

Experimental: Arm 3: Treatment naive (ASV + DCV) - [Subjects will receive ASV + DCV for 24 weeks] followed by ASV + DCV for 24 weeks in protocol AI444026]
Subjects meeting prespecified rescue criteria in the treatment naive cohort may have therapeutic rescue instituted with QUAD regimen (QUAD= ASV + DCV + P/R)
Asunaprevir 100 mg Capsules by mouth, Twice daily for 24 or 48 Weeks
Daclatasvir 60 mg Tablet by mouth, Once daily for 24 or 48 Weeks
Pegylated-interferon alfa 2a (PegIFN) 180 mcg/0.5 mL injection subcutaneously (SC), once weekly for 24 or 48 weeks
Ribavirin 1000 mg/1200 mg (total daily dose) tablet by mouth for 24 or 48 weeks

Experimental: Arm 4: Null or Partial Responder to P/R (ASV + DCV) 24/48 week - Subjects meeting prespecified rescue criteria in the null or partial responder cohort or active arm of the treatment naive cohort may have therapeutic rescue instituted with QUAD regimen (QUAD= ASV + DCV + P/R)
Asunaprevir 100 mg Capsules by mouth, Twice daily for 24 or 48 Weeks
Daclatasvir 60 mg Tablet by mouth, Once daily for 24 or 48 Weeks
Pegylated-interferon alfa 2a (PegIFN) 180 mcg/0.5 mL injection subcutaneously (SC), once weekly for 24 or 48 weeks
Ribavirin 1000 mg / 1200 mg (total daily dose) Tablet by mouth, for 24 or 48 weeks


Treatment: Drugs: Asunaprevir (ASV)


Treatment: Drugs: Daclatasvir (DCV)


Treatment: Drugs: Pegylated-interferon alfa 2a (PegIFN)


Treatment: Drugs: Ribavirin (RBV)
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Proportion of treated subjects with SVR12, defined as HCV RNA < LOQ at post treatment Week 12, for subjects who are prior null or partial responders to P/R or are treatment-naive
Timepoint [1] 0 0
At 12 weeks post-treatment
Secondary outcome [1] 0 0
Proportion of treated subjects with SVR12, defined as HCV RNA < LOQ at post-treatment Week 12, for subjects who are intolerant or ineligible to P/R
Timepoint [1] 0 0
Post-treatment Week 12
Secondary outcome [2] 0 0
On treatment safety, as measured by frequency of Serious Adverse Events (SAEs) and discontinuations due to Adverse Events (AEs)
Timepoint [2] 0 0
End of Treatment (up to 48 weeks) plus 7 days
Secondary outcome [3] 0 0
Differences in rates of selected grade 3-4 laboratory abnormalities during the first 12 weeks between treatments (ASV + DCV vs PBO) for naive subjects
Timepoint [3] 0 0
Up to first 12 weeks
Secondary outcome [4] 0 0
Proportion of genotype 1b subjects with SVR12 (HCV RNA < LOQ at post treatment Week 12) by the rs12979860 single nucleotide polymorphisms (SNP) in the IL28B gene for each cohort
Timepoint [4] 0 0
Post-treatment Week 12
Secondary outcome [5] 0 0
Proportion of genotype 1b subjects with HCV RNA undetectable
Timepoint [5] 0 0
At weeks 1, 2, 4, 6, 8 and 12; at both Weeks 4 and 12 [eRVR]; EOT (up to 24 weeks), post-treatment Week 12, or post-treatment Week 24 for each cohort
Secondary outcome [6] 0 0
Proportion of genotypes 1b subjects with HCV RNA < LOQ
Timepoint [6] 0 0
At weeks 1, 2, 4, 6, 8 and 12; at both Weeks 4 and 12 [VR(4&12)]; EOT (up to 24 weeks), post-treatment Week 24 (SVR24) for each cohort
Secondary outcome [7] 0 0
Proportion of subjects with anemia
Timepoint [7] 0 0
At 12 weeks post-treatment
Secondary outcome [8] 0 0
Proportion of subjects with rash
Timepoint [8] 0 0
At 12 weeks post-treatment

Eligibility
Key inclusion criteria
For more information regarding BMS clinical trial participation, please visit
www.BMSStudyConnect.com



- Males and females, = 18 years of age

- HCV Genotype 1b who previously failed treatment with peginterferon alfa and ribavirin,
classified as previous null or partial responders based on previous therapy, OR
intolerant or ineligible to P/R due to neutropenia, anemia, depression or
thrombocytopenia with fibrosis/cirrhosis, OR treatment naive

- HCV RNA = 10,000 IU/mL

- Seronegative for Human immunodeficiency virus (HIV) and Hepatitis B surface antigen
(HBsAg)

- Subjects with compensated cirrhosis are permitted (compensated cirrhotics are capped
at approximately 25% of treated population)
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Prior treatment of HCV with HCV direct acting antiviral (DAA)

- Evidence of a medical condition contributing to chronic liver disease other than HCV

- Evidence of decompensated liver disease including, but not limited to, a history or
presence of ascites, bleeding varices, or hepatic encephalopathy

- Diagnosed or suspected hepatocellular carcinoma or other malignancies

- Uncontrolled diabetes or hypertension

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/05/2012
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/09/2014
Sample size
Target
Accrual to date
Final
748
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Local Institution - Darlinghurst
Recruitment hospital [2] 0 0
Local Institution - Kogarah
Recruitment hospital [3] 0 0
Local Institution - Randwick
Recruitment hospital [4] 0 0
Local Institution - Fitzroy
Recruitment hospital [5] 0 0
Local Institution - Adelaide
Recruitment hospital [6] 0 0
Local Institution - Bedford Park, Sa
Recruitment hospital [7] 0 0
Local Institution - Clayton
Recruitment hospital [8] 0 0
Local Institution - Heidelberg
Recruitment hospital [9] 0 0
Local Institution - Melbourne
Recruitment hospital [10] 0 0
Local Institution - Fremantle
Recruitment hospital [11] 0 0
Local Institution - Nedlands
Recruitment hospital [12] 0 0
Local Institution - Perth
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
2217 - Kogarah
Recruitment postcode(s) [3] 0 0
2070 - Randwick
Recruitment postcode(s) [4] 0 0
3065 VIC - Fitzroy
Recruitment postcode(s) [5] 0 0
5000 - Adelaide
Recruitment postcode(s) [6] 0 0
5042 - Bedford Park, Sa
Recruitment postcode(s) [7] 0 0
3168 - Clayton
Recruitment postcode(s) [8] 0 0
3084 - Heidelberg
Recruitment postcode(s) [9] 0 0
3004 - Melbourne
Recruitment postcode(s) [10] 0 0
6160 - Fremantle
Recruitment postcode(s) [11] 0 0
6009 - Nedlands
Recruitment postcode(s) [12] 0 0
6001 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Maryland
Country [6] 0 0
United States of America
State/province [6] 0 0
Massachusetts
Country [7] 0 0
United States of America
State/province [7] 0 0
Michigan
Country [8] 0 0
United States of America
State/province [8] 0 0
Missouri
Country [9] 0 0
United States of America
State/province [9] 0 0
New York
Country [10] 0 0
United States of America
State/province [10] 0 0
North Carolina
Country [11] 0 0
United States of America
State/province [11] 0 0
Texas
Country [12] 0 0
United States of America
State/province [12] 0 0
Wisconsin
Country [13] 0 0
Argentina
State/province [13] 0 0
Buenos Aires
Country [14] 0 0
Argentina
State/province [14] 0 0
Santa Fe
Country [15] 0 0
Austria
State/province [15] 0 0
Graz
Country [16] 0 0
Austria
State/province [16] 0 0
Linz
Country [17] 0 0
Austria
State/province [17] 0 0
Salzburg
Country [18] 0 0
Austria
State/province [18] 0 0
Wien
Country [19] 0 0
Canada
State/province [19] 0 0
British Columbia
Country [20] 0 0
Canada
State/province [20] 0 0
Ontario
Country [21] 0 0
Canada
State/province [21] 0 0
Quebec
Country [22] 0 0
France
State/province [22] 0 0
Clichy Cedex
Country [23] 0 0
France
State/province [23] 0 0
Creteil
Country [24] 0 0
France
State/province [24] 0 0
Lyon Cedex 04
Country [25] 0 0
France
State/province [25] 0 0
Marseille Cedex 08
Country [26] 0 0
France
State/province [26] 0 0
Paris Cedex 13
Country [27] 0 0
France
State/province [27] 0 0
Paris
Country [28] 0 0
France
State/province [28] 0 0
Toulouse
Country [29] 0 0
France
State/province [29] 0 0
Vandoeuvre Les Nancy
Country [30] 0 0
Germany
State/province [30] 0 0
Berlin
Country [31] 0 0
Germany
State/province [31] 0 0
Bonn
Country [32] 0 0
Germany
State/province [32] 0 0
Essen
Country [33] 0 0
Germany
State/province [33] 0 0
Frankfurt
Country [34] 0 0
Germany
State/province [34] 0 0
Hamburg
Country [35] 0 0
Germany
State/province [35] 0 0
Hannover
Country [36] 0 0
Germany
State/province [36] 0 0
Muenchen
Country [37] 0 0
Ireland
State/province [37] 0 0
Dublin
Country [38] 0 0
Israel
State/province [38] 0 0
Haifa
Country [39] 0 0
Israel
State/province [39] 0 0
Jerusalem
Country [40] 0 0
Israel
State/province [40] 0 0
Tel Aviv
Country [41] 0 0
Israel
State/province [41] 0 0
Tel Hashomer
Country [42] 0 0
Israel
State/province [42] 0 0
Zafed
Country [43] 0 0
Italy
State/province [43] 0 0
Messina
Country [44] 0 0
Italy
State/province [44] 0 0
Milano
Country [45] 0 0
Italy
State/province [45] 0 0
Roma
Country [46] 0 0
Italy
State/province [46] 0 0
Torino
Country [47] 0 0
Korea, Republic of
State/province [47] 0 0
Busan
Country [48] 0 0
Korea, Republic of
State/province [48] 0 0
Daegu
Country [49] 0 0
Korea, Republic of
State/province [49] 0 0
Gyeonggi-do
Country [50] 0 0
Korea, Republic of
State/province [50] 0 0
Gyeongsangnam-do
Country [51] 0 0
Korea, Republic of
State/province [51] 0 0
Incheon
Country [52] 0 0
Korea, Republic of
State/province [52] 0 0
Seoul
Country [53] 0 0
Netherlands
State/province [53] 0 0
Amsterdam
Country [54] 0 0
Netherlands
State/province [54] 0 0
Leiden
Country [55] 0 0
Netherlands
State/province [55] 0 0
Rotterdam
Country [56] 0 0
New Zealand
State/province [56] 0 0
Auckland
Country [57] 0 0
New Zealand
State/province [57] 0 0
Hamilton
Country [58] 0 0
New Zealand
State/province [58] 0 0
Wellington
Country [59] 0 0
Poland
State/province [59] 0 0
Bialystok
Country [60] 0 0
Poland
State/province [60] 0 0
Wroclaw
Country [61] 0 0
Russian Federation
State/province [61] 0 0
Chelyabinsk
Country [62] 0 0
Russian Federation
State/province [62] 0 0
Krasnoyarsk
Country [63] 0 0
Russian Federation
State/province [63] 0 0
Moscow
Country [64] 0 0
Russian Federation
State/province [64] 0 0
Saint-Petersburg
Country [65] 0 0
Russian Federation
State/province [65] 0 0
Samara
Country [66] 0 0
Russian Federation
State/province [66] 0 0
Smolensk
Country [67] 0 0
Russian Federation
State/province [67] 0 0
Tyumen
Country [68] 0 0
Spain
State/province [68] 0 0
Alicante
Country [69] 0 0
Spain
State/province [69] 0 0
Barcelona
Country [70] 0 0
Spain
State/province [70] 0 0
Madrid
Country [71] 0 0
Spain
State/province [71] 0 0
Valencia
Country [72] 0 0
Taiwan
State/province [72] 0 0
Taichung
Country [73] 0 0
Taiwan
State/province [73] 0 0
Tainan
Country [74] 0 0
Taiwan
State/province [74] 0 0
Taipei
Country [75] 0 0
United Kingdom
State/province [75] 0 0
Greater London
Country [76] 0 0
United Kingdom
State/province [76] 0 0
Greater Manchester
Country [77] 0 0
United Kingdom
State/province [77] 0 0
Lanarkshire

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Bristol-Myers Squibb
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to estimate efficacy, as determined by the proportion of
subjects with Sustained virologic response at post-treatment Week 12 (SVR12), defined as
Hepatitis C virus (HCV) Ribonucleic acid (RNA) < Limit of quantitation (LOQ) at
post-treatment Week 12, for subjects who are prior null or partial responders to P/R or who
are treatment-naive.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01581203
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Bristol-Myers Squibb
Address 0 0
Bristol-Myers Squibb
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01581203