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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/NCT01858961




Registration number
NCT01858961
Ethics application status
Date submitted
17/05/2013
Date registered
21/05/2013
Date last updated
23/01/2014

Titles & IDs
Public title
Open Label Trial to Compare BI 207127 to Telaprevir in HCV Patients
Scientific title
A Phase III, Randomised, Open Label, Active-controlled Study of an Interferon-free Regimen of BI 207127 in Combination With Faldaprevir and Ribavirin Compared to Telaprevir in Combination With Pegylated interferon-a and Ribavirin in Treatment-naive Patients With Chronic Genotype 1b Hepatitis C Virus Infection
Secondary ID [1] 0 0
2012-004544-30
Secondary ID [2] 0 0
1241.37
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hepatitis C, Chronic 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 - BI 201335
Treatment: Drugs - ribavirin
Treatment: Drugs - BI 207127
Treatment: Drugs - Telaprevir
Treatment: Drugs - ribavirin
Treatment: Drugs - Pegylated Interferon

Experimental: Group 1 - BI 201335 in combination with BI 207127 and ribavirin for 24 weeks

Experimental: Group 2 - Telaprevir in combination with PegIFN and ribavirin for 24 weeks or 48 weeks


Treatment: Drugs: BI 201335
Once a day

Treatment: Drugs: ribavirin
Twice a day

Treatment: Drugs: BI 207127
Twice a day

Treatment: Drugs: Telaprevir
Three times a day

Treatment: Drugs: ribavirin
Twice a day

Treatment: Drugs: Pegylated Interferon
Once a week
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Sustained Virologic Response at Week 12 after end of treatment (SVR12)
Timepoint [1] 0 0
at week 12 post treatment
Secondary outcome [1] 0 0
SVR4: Plasma HCV RNA level <25 IU/mL1 at 4 weeks after end of treatment
Timepoint [1] 0 0
at week 4 post treatment
Secondary outcome [2] 0 0
SVR24: Plasma HCV RNA level <25 IU/mL1 at 24 weeks after end of treatment
Timepoint [2] 0 0
at week 4 post treatment
Secondary outcome [3] 0 0
Virological Response at Week 4 -Plasma HCV RNA level undetectable at Week 4 -Plasma HCV RNA level <25 IU/mL at Week 4
Timepoint [3] 0 0
at week 4 post treatment
Secondary outcome [4] 0 0
Plasma HCV level undetectable at Week 12
Timepoint [4] 0 0
at week 12
Secondary outcome [5] 0 0
Time to achieving HCV RNA undetectable
Timepoint [5] 0 0
up to week 48
Secondary outcome [6] 0 0
Virological breakthrough
Timepoint [6] 0 0
up to week 48
Secondary outcome [7] 0 0
ETR: Plasma HCV RNA level undetected at the end of treatment
Timepoint [7] 0 0
week 24 or 48
Secondary outcome [8] 0 0
Lack of on-treatment viral response
Timepoint [8] 0 0
up to week 48
Secondary outcome [9] 0 0
Relapse
Timepoint [9] 0 0
up to 48 weeks post treatment
Secondary outcome [10] 0 0
Adverse events
Timepoint [10] 0 0
up to week 48 post treatment
Secondary outcome [11] 0 0
Adverse events leading to discontinuation
Timepoint [11] 0 0
up to week 48
Secondary outcome [12] 0 0
Serious Adverse Events
Timepoint [12] 0 0
up to week 48 post treatment
Secondary outcome [13] 0 0
Laboratory test abnormalities by DAIDS grades
Timepoint [13] 0 0
up to week 48 post treatment
Secondary outcome [14] 0 0
Rate of red blood cell transfusion
Timepoint [14] 0 0
up to week 48 post treatment
Secondary outcome [15] 0 0
Time to discontinuation of trial medication
Timepoint [15] 0 0
up to week 48
Secondary outcome [16] 0 0
Liver disease progression, fibroscan and FibroSURE
Timepoint [16] 0 0
up to week 48 post treatment
Secondary outcome [17] 0 0
Rate of ESA use
Timepoint [17] 0 0
up to week 48 post treatment
Secondary outcome [18] 0 0
Change in laboratory test values over time
Timepoint [18] 0 0
up to week 48 post treatment
Secondary outcome [19] 0 0
Patients requiring hospitalisation due to AEs related to study drugs
Timepoint [19] 0 0
up to week 48 post treatment

Eligibility
Key inclusion criteria
Inclusion criteria:

1. Chronic HCV, diagnosed by HCV RNA = 1,000 IU/mL at screening in addition to at least
one of the following:

1. positive anti-HCV antibodies or detected HCV RNA at least 6 months prior to
screening, OR

2. liver biopsy indicating chronic HCV infection, OR

3. history of elevated ALT levels at least 6 months prior to screening.

2. HCV infection of sub-GT1b confirmed by genotypic testing at screening.

3. Treatment naïve defined as:

1. no prior treatment with any interferon, pegylated interferon, and /or ribavirin
and

2. no prior treatment with at least one dose of any other licensed or
investigational antiviral agent for acute or chronic hepatitis C infection.

4. Availability of a liver biopsy within three years or fibroscan within 6 months prior
to randomisation.

Note: patients who do not have a liver biopsy (nor fibroscan) due to contraindication
of the procedure should not be excluded for this reason. The decision on the inclusion
of these patients should be discussed with the CML. Patients with a liver biopsy
performed 3 or more years (or fibroscan performed 6 months or more) prior to
randomisation, demonstrating cirrhosis do not need to repeat a liver biopsy or
fibroscan.

5. Age 18 - 70 years (inclusive).

6. Female patients

1. with documented hysterectomy, or

2. who have had both ovaries removed, or

3. with documented tubal ligation, or

4. who are post-menopausal with last menstrual period at least 12 months prior to
screening, or

5. of childbearing potential with a negative serum pregnancy test at screening and
on Day 1 (Visit 2), who agree to use two non-hormonal methods of birth control
from the date of screening until 7 months after the last dose of ribavirin. They
must not breast-feed at any time from the date of screening until 7 months after
the last dose of ribavirin.

Accepted methods of contraception for females in this trial are diaphragm with
spermicide substances, intrauterine devices, cervical caps and condoms.

Note: Systemic hormonal contraceptives may not be as effective in women taking BI
207127/FDV combination therapy and are not accepted methods of contraception in the
study.

OR:

Male patients

1. who are documented to be sterile, or

2. who consistently and correctly use a condom while their female partners (if of
child-bearing potential) agree to use one of the appropriate medically accepted
methods of birth control from the date of screening until 7 months after the last
dose of ribavirin, and

3. without pregnant female partners. It is in the responsibility of the male patient
to ensure that his partner (or partners) is not pregnant prior to enrolment into
the study or becomes pregnant during the treatment and follow-up phase. Female
partners of childbearing potential must perform monthly pregnancy tests from the
date of screening until 7 months after the last dose of ribavirin (tests will be
provided by the Sponsor).

7. Signed informed consent form prior to trial participation.
Minimum age
18 Years
Maximum age
70 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:

1. HCV infection of mixed genotype (1/2, 1/3, and 1/4), HCV sub-GT1a or GT1 undefined,
diagnosed at screening by genotypic testing.

2. Liver disease due to causes other than chronic HCV infection which may include but is
not limited to hemochromatosis, Wilson's disease, or autoimmune liver disease.

3. HIV infection.

4. Hepatitis B virus (HBV) infection based on presence of Hepatitis B surface antigen.

5. Evidence of decompensated liver disease or history of decompensated liver disease,
defined as history of ascites, hepatic encephalopathy, bleeding esophageal varices or
any other evidence of previous decompensation and/or any laboratory results
(International Normalised Ratio, albumin, bilirubin) indicating a Child-Pugh-Turcotte
score > 6 points (i.e. CPT-B or -C)

6. Confirmed or suspected active malignancy or history of malignancy within the last 5
years (with the exception of appropriately treated basal cell carcinoma of the skin or
in situ carcinoma of the uterine cervix).

7. Patients with ongoing or historical photosensitivity or recurrent rash.

8. History of illicit drug use (other than cannabis) or chronic alcohol abuse within 12
months prior to randomization, in the opinion of the Investigator.

9. Body mass index <18 or >35 kg/m2.

10. Usage of any investigational drugs within 28 days prior to randomisation, or the
planned usage of an investigational drug during the course of the current study.

11. Known hypersensitivity to any ingredient of the study drugs.

12. A condition that is insufficiently diagnosed, treated or clinically unstable which in
the opinion of Investigator may put the patient at risk because of participation in
this study, influence the results of this study, or limit the patient's ability to
participate in this study.

13. Alpha fetoprotein value >100ng/mL at screening; if > 20ng/mL and = 100ng/mL, patients
can be included if there is no evidence of liver cancer in an appropriate imaging
study within 6 months prior to randomisation.

14. A history of severe pre-existing cardiac disease, including unstable or uncontrolled
cardiac disease (e.g. congestive heart failure, myocardial infarction, unstable angina
and arrhythmic disorders) current or within the previous 12 months before
randomisation. Clinically significant Electrocardiogram (ECG) abnormalities. A history
of congenital QT prolongation, or a family history of congenital QT prolongation or
sudden death.

15. Received silymarin (milk thistle) or glycyrrhizin or Sho-saiko-to (SST) within 28 days
prior to randomisation or any medication listed in a restricted medication list
provided in ISF within 28 days prior to randomisation, with the exception of
parenteral analgesics used during liver biopsy procedure.

16. Pre-existing psychiatric conditions that could interfere with the subject's
participation in and completion of the study including but not limited to severe
depression or hospitalization for depression, suicidal ideation and attempted suicide,
schizophrenia, bipolar illness, severe anxiety or personality disorder, history of
craniocerebral trauma or active seizure disorders requiring medication, a period of
disability or impairment due to a psychiatric disease current or within the previous 3
years before randomisation.

17. Abnormal thyroid function that cannot be controlled effectively by medication.

18. Active autoimmune-mediated disease (e.g., Crohn's disease, ulcerative colitis,
idiopathic thrombocytopenic purpura, systemic lupus erythematosus, autoimmune
hemolytic anemia, scleroderma, severe psoriasis).

19. Requirement for chronic systemic corticosteroids (inhaled or nasally administered or
pulmonary steroids will be allowed).

20. History or other evidence of severe retinopathy or clinically significant
ophthalmological disorder due to diabetes mellitus or hypertension (but not limited to
these conditions).

Plus other exclusion criteria relating to Peg interferon, ribavirin and Telaprevir.

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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Withdrawn
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
1/05/2013
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/07/2016
Actual
Sample size
Target
Accrual to date
Final
0
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 0 0
1241.37.61002 Boehringer Ingelheim Investigational Site - Westmead
Recruitment hospital [2] 0 0
1241.37.61001 Boehringer Ingelheim Investigational Site - Adelaide
Recruitment hospital [3] 0 0
1241.37.61003 Boehringer Ingelheim Investigational Site - Fitzroy
Recruitment postcode(s) [1] 0 0
- Westmead
Recruitment postcode(s) [2] 0 0
- Adelaide
Recruitment postcode(s) [3] 0 0
- Fitzroy
Recruitment outside Australia
Country [1] 0 0
Spain
State/province [1] 0 0
Alzira
Country [2] 0 0
Spain
State/province [2] 0 0
Barcelona
Country [3] 0 0
Spain
State/province [3] 0 0
L'Hospitalet Llobregat (BCN)
Country [4] 0 0
Spain
State/province [4] 0 0
Madrid
Country [5] 0 0
Spain
State/province [5] 0 0
Valencia
Country [6] 0 0
Sweden
State/province [6] 0 0
Lund
Country [7] 0 0
Sweden
State/province [7] 0 0
Stockholm

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Boehringer Ingelheim
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The aim of this trial is to evaluate efficacy and safety of treatment with 600 mg of BID BI
207127 in combination with 120 mg QD Faldaprevir and RBV compared to a Telaprevir-based
regimen along with PegIFN and RBV in chronically infected HCV GT1 treatment naïve patients,
including patients with compensated cirrhosis.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01858961
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Boehringer Ingelheim
Address 0 0
Boehringer Ingelheim
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/NCT01858961