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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/NCT02569710




Registration number
NCT02569710
Ethics application status
Date submitted
1/10/2015
Date registered
7/10/2015
Date last updated
16/07/2019

Titles & IDs
Public title
A Study to Evaluate the Safety, Pharmacokinetics and Efficacy of the Combination of AL-335, Odalasvir, and Simeprevir
Scientific title
A Phase 2a, Open-Label Study to Evaluate the Safety, Pharmacokinetics and Efficacy of the Combination of AL-335 and Odalasvir, With or Without Simeprevir, in Treatment-Naïve Subjects With Genotype 1, 2 or 3 Chronic Hepatitis C Infection With or Without Compensated Child Pugh A Cirrhosis
Secondary ID [1] 0 0
AL-335-604
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Hepatitis C 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 - AL-335
Treatment: Drugs - Odalasvir (ODV)
Treatment: Drugs - Simeprevir (SMV)

Experimental: Cohorts 1 and 2 (Without Cirrhosis) : AL-335+ODV+SMV - Treatment-naïve non-cirrhotic Hepatitis C virus (HCV)-infected participants will receive AL-335 and Odalasvir (ODV) with Simeprevir (SMV) for 8 weeks.

Experimental: Cohort 1b (Without Cirrhosis) : AL-335+ODV - Treatment-naïve non-cirrhotic HCV-infected participants will receive AL-335 and ODV for 8 weeks.

Experimental: Cohort 3 (Without Cirrhosis) : AL-335+ODV+SMV - Treatment-naïve non-cirrhotic HCV-infected participants will receive AL-335 and ODV with SMV for 6 weeks.

Experimental: Cohort 4 (Without Cirrhosis) : AL-335+ODV - Treatment-naïve non-cirrhotic HCV-infected participants will receive AL-335 and ODV up to 8 or 12 weeks.

Experimental: Cohort 5 (Without Cirrhosis) : AL-335+ODV + SMV - Treatment-naïve non-cirrhotic HCV-infected participants will receive AL-335 and ODV with SMV up to 8 or 12 weeks.

Experimental: Cohorts 6, 7, 8 and 12 (With Cirrhosis) : AL-335+ODV+SMV - Treatment naïve or treatment experienced HCV-infected participants with compensated cirrhosis will receive AL-335 and ODV with SMV for 8 weeks.

Experimental: Cohorts 9, 10 and 11 (With Cirrhosis) : AL-335+ODV+SMV - Treatment naïve or treatment experienced HCV-infected participants with compensated cirrhosis will receive AL-335 and ODV with SMV for 12 weeks.

Experimental: Cohorts 12 to 15: AL-335+ODV With/without SMV - Based on safety, pharmacokinetic (PK), and viral load data, the treatment duration (4 to 12 weeks) and dose levels (AL-335: 400-1,200 milligram [mg], ODV: 25-50 mg with/without SMV: 75-150 mg) may be changed for ongoing and future cohorts (up to 15) after obtaining agreement from the Sponsor and the Principal Investigator.


Treatment: Drugs: AL-335
AL-335 tablets will be administered in a dose range of 400 to 1200 mg once daily (QD).

Treatment: Drugs: Odalasvir (ODV)
ODV capsules will be administered in a dose range of 25 to 50 mg.

Treatment: Drugs: Simeprevir (SMV)
SMV tablets will be administered in a dose range of 75 to 150 mg QD or every other day (QOD).
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Treatment Emergent Adverse Event (TEAE)
Timepoint [1] 0 0
Up to 43 weeks
Primary outcome [2] 0 0
Body Weight at End of Treatment
Timepoint [2] 0 0
End of treatment (Cohort 3: 6 weeks; Cohort 1, Cohort 1b+ Cohort 4, Cohort 2, Cohort 5a, and Cohort 6, 7, 8: 8 weeks; Cohort 4, Cohort 5b, Cohort 9 and Cohort 11: 12 weeks)
Primary outcome [3] 0 0
Body Mass Index (BMI) at End of Treatment
Timepoint [3] 0 0
End of treatment (Cohort 3: 6 weeks; Cohort 1, Cohort 1b+ Cohort 4, Cohort 2, Cohort 5a, and Cohort 6, 7, 8: 8 weeks; Cohort 4, Cohort 5b, Cohort 9 and Cohort 11: 12 weeks)
Primary outcome [4] 0 0
Percentage of Participants With Worst Post-Baseline Values of Vital Signs
Timepoint [4] 0 0
Up to 43 weeks
Primary outcome [5] 0 0
Percentage of Participants With Maximum Decrease From Baseline in Mean Ejection Fraction
Timepoint [5] 0 0
Baseline up to End of treatment (up to 43 weeks)
Primary outcome [6] 0 0
Percentage of Participants by Treatment Emergent Toxicity Grade - Hematology Parameters
Timepoint [6] 0 0
Up to 43 weeks
Primary outcome [7] 0 0
Percentage of Participants by Treatment Emergent Toxicity Grade - Blood Chemistry Parameters
Timepoint [7] 0 0
Up to 43 weeks
Primary outcome [8] 0 0
Percentage of Participants by Treatment Emergent Toxicity Grade - Prothrombin International Normalized Ratio (INR)
Timepoint [8] 0 0
Up to 43 weeks
Primary outcome [9] 0 0
Percentage of Participants by Treatment Emergent Toxicity Grade - Urinalysis Parameter (Protein)
Timepoint [9] 0 0
Up to 43 weeks
Primary outcome [10] 0 0
Percentage of Participants With Worst Treatment Emergent Abnormalities of Electrocardiogram (ECG) Parameters
Timepoint [10] 0 0
Up to 43 weeks
Secondary outcome [1] 0 0
Percentage of Participants With Sustained Virologic Response (SVR) at Week 4, 12 and 24 After End of Treatment
Timepoint [1] 0 0
At Week 4, 12 and Week 24 after end of treatment (Cohort 3: 6 weeks; Cohort 1, Cohort 1b+ Cohort 4, Cohort 2, Cohort 5a, and Cohort 6, 7, 8: 8 weeks; Cohort 4, Cohort 5b, Cohort 9 and Cohort 11: 12 weeks)
Secondary outcome [2] 0 0
Minimum Observed Plasma Concentration (Cmin) of AL-335 and Its Metabolites (ALS-022399 and ALS-022227)
Timepoint [2] 0 0
Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)
Secondary outcome [3] 0 0
Maximum Observed Plasma Concentration (Cmax) of AL-335 and Its Metabolites (ALS-022399 and ALS-022227)
Timepoint [3] 0 0
Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)
Secondary outcome [4] 0 0
Trough Plasma Concentration (Ctrough) for AL-335 and Its Metabolites (ALS-022399 and ALS-022227)
Timepoint [4] 0 0
Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)
Secondary outcome [5] 0 0
Time to Reach the Maximum Plasma Concentration (Tmax) of AL-335 and Its Metabolites (ALS-022399 and ALS-022227)
Timepoint [5] 0 0
Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)
Secondary outcome [6] 0 0
Area Under the Plasma Concentration-Time Curve From Time 0 to Last Measurable Plasma Concentration (AUC [0-last]) of AL-335 and Its Metabolites (ALS-022399 and ALS-022227)
Timepoint [6] 0 0
Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)
Secondary outcome [7] 0 0
Area Under the Plasma Concentration Time-Curve at 24 Hours (AUC0-24) for AL-335 and Its Metabolites (ALS-022399 and ALS-022227)
Timepoint [7] 0 0
Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose
Secondary outcome [8] 0 0
Last Measurable Plasma Concentration (Clast) of AL-335 and Its Metabolite (ALS-022399 and ALS-022227)
Timepoint [8] 0 0
Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)
Secondary outcome [9] 0 0
Time Corresponding to Last Measurable Plasma Concentration (Tlast) for AL-335 and Its Metabolites (ALS-022399 and ALS-022227)
Timepoint [9] 0 0
Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)
Secondary outcome [10] 0 0
Average Plasma Concentration at Steady State (Css,Avg) of ALS-022227
Timepoint [10] 0 0
Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)
Secondary outcome [11] 0 0
Cmin of Simeprevir
Timepoint [11] 0 0
Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)
Secondary outcome [12] 0 0
Cmax of Simeprevir
Timepoint [12] 0 0
Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)
Secondary outcome [13] 0 0
Ctrough of Simeprevir
Timepoint [13] 0 0
Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)
Secondary outcome [14] 0 0
Tmax of Simeprevir
Timepoint [14] 0 0
Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)
Secondary outcome [15] 0 0
AUC (0-last) of Simeprevir
Timepoint [15] 0 0
Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)
Secondary outcome [16] 0 0
AUC (0-24) of Simeprevir
Timepoint [16] 0 0
Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose
Secondary outcome [17] 0 0
Clast of Simeprevir
Timepoint [17] 0 0
Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)
Secondary outcome [18] 0 0
Tlast of Simeprevir
Timepoint [18] 0 0
Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)
Secondary outcome [19] 0 0
Average Plasma Concentration at Steady State (Css,Avg) of Simeprevir
Timepoint [19] 0 0
Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)
Secondary outcome [20] 0 0
Cmin of Odalasvir
Timepoint [20] 0 0
Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)
Secondary outcome [21] 0 0
Cmax of Odalasvir
Timepoint [21] 0 0
Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)
Secondary outcome [22] 0 0
Ctrough of Odalasvir
Timepoint [22] 0 0
Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)
Secondary outcome [23] 0 0
Tmax of Odalasvir
Timepoint [23] 0 0
Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)
Secondary outcome [24] 0 0
AUC (0-last) of Odalasvir
Timepoint [24] 0 0
Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)
Secondary outcome [25] 0 0
AUC (0-24) for Odalasvir
Timepoint [25] 0 0
Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose
Secondary outcome [26] 0 0
Clast of Odalasvir
Timepoint [26] 0 0
Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)
Secondary outcome [27] 0 0
Tlast of Odalasvir
Timepoint [27] 0 0
Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)
Secondary outcome [28] 0 0
Average Plasma Concentration at Steady State (Css,Avg) of Odalasvir
Timepoint [28] 0 0
Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)
Secondary outcome [29] 0 0
Percentage of Participants With Virologic Relapse During the Follow-up Period
Timepoint [29] 0 0
Follow up period (Up to Week 12 after end of treatment)
Secondary outcome [30] 0 0
Percentage of Participants With On-treatment Failure
Timepoint [30] 0 0
Up to 12 weeks
Secondary outcome [31] 0 0
Percentage of Participants Who Achieved HCV RNA Less Then (<) LLOQ Undetectable
Timepoint [31] 0 0
Day 2, 3, Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 and End of treatment (Cohort 3: 6 weeks; Cohort 1, Cohort 1b+ Cohort 4, Cohort 2, Cohort 5a, and Cohort 6, 7, 8: 8 weeks; Cohort 4, Cohort 5b, Cohort 9 and Cohort 11: 12 weeks)
Secondary outcome [32] 0 0
Percentage of Participants Who Achieved HCV RNA <LLOQ
Timepoint [32] 0 0
Day 2, 3, Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 and End of treatment (Cohort 3: 6 weeks; Cohort 1, Cohort 1b+ Cohort 4, Cohort 2, Cohort 5a, and Cohort 6, 7, 8: 8 weeks; Cohort 4, Cohort 5b, Cohort 9 and Cohort 11: 12 weeks)
Secondary outcome [33] 0 0
Time to Achieve Undetectable HCV RNA or < LLOQ HCV RNA
Timepoint [33] 0 0
Up to Week 24 (follow up visit)
Secondary outcome [34] 0 0
Number of Participants With HCV Nonstructural Protein NS5A, NS5B, and NS3/4A Sequence in Participants With Virologic Failure
Timepoint [34] 0 0
Up to Week 24 (Follow up visit)

Eligibility
Key inclusion criteria
1. Participant has provided written consent

2. In the Investigator's opinion, the participant is able to understand and comply with
protocol requirements, instructions, and protocol stated restrictions and is likely to
complete the study as planned

3. Male or female, 18-70 years of age

4. Body mass index (BMI) 18-35 kilogram per meter square (kg/m^2), inclusive

5. A woman of childbearing potential must have a negative serum (beta-human chorionic
gonadotropin) pregnancy test at screening

6. Female participants must either:

- not be of childbearing potential defined as: i. Postmenopausal for at least 12
months (that is [i.e.], 2 years of amenorrhea without an alternative medical
cause) and a serum follicle stimulating hormone (FSH) level in the postmenopausal
range (per reference laboratory), OR ii. Surgically sterile (example [e.g.],
underwent total hysterectomy, bilateral oophorectomy, or bilateral tubal
ligation/bilateral tubal clips without reversal operation), or otherwise
incapable of becoming pregnant, OR

- be of childbearing potential AND

- not heterosexually active (e.g., abstinent or homosexual) from screening until 6
months after study drug administration (or longer, if dictated by local
regulations), OR

- if heterosexually active

- have a vasectomized partner (confirmed sterile per verbal account of the
participant), OR

- using an acceptable method of birth control from screening and agree to
continue to use the same method of contraception throughout the study and
for 6 months after study drug administration (or longer, if dictated by
local regulations). Oral hormone based contraceptives are not allowed from
14 days before the planned study drug administration until 6 months after
the last dose of treatment due to the potential for drug-drug interactions
which might undermine their efficacy. An intrauterine device (IUD), being
either hormonal (i.e., Intra-Uterine System [IUS*]) or non-hormonal, is
considered highly effective and reliable; therefore participants using an
IUD/IUS are not required to use additional contraceptive methods (no
double-barrier method is required). Other non-oral hormone-based
contraception methods (e.g., injectable, implants, transdermal system,
vaginal ring) may be continued, but as the interaction of the study drug
with hormone-based contraception is unknown, these methods are not
considered to be reliable and therefore participants should use a
double-barrier method (e.g., male condom+either diaphragm or cervical cap
with or without spermicide).

- An IUS does not rely on systemic plasma concentrations and is therefore
not expected to be impacted by a potential drug-drug interaction (DDI)

Note 1: Sexual abstinence is considered a highly effective method only if defined as
refraining from heterosexual intercourse during the entire period of risk associated
with the study drug. The reliability of sexual abstinence needs to be evaluated in
relation to the duration of the study and the preferred and usual lifestyle of the
participant.

Note 2: A male and female condom should not be used together due to risk of breakage
or damage caused by latex friction

7. A post-menopausal female who is receiving hormone replacement therapy and is willing
to discontinue hormone therapy 30 days before study drug dosing and agrees to remain
off hormone replacement therapy for the duration of the study may be eligible for
study participation.

- Male participants must either:

- be surgically sterile (had a vasectomy), or otherwise incapable of fathering a
child, OR

- not be heterosexually active (e.g., abstinent or homosexual) from enrollment (Day
1) in the study until at least 6 months after study drug administration, OR

- if heterosexually active:

- have a partner who is postmenopausal (2 years amenorrhea), surgically
sterile (e.g., has had a total hysterectomy, bilateral oophorectomy, or
bilateral tubal ligation/bilateral tubal clips without reversal operation),
or otherwise incapable of becoming pregnant OR

- be practicing an acceptable method of birth control from enrollment in the
study (Day 1) and agree to continue to use the same method of contraception
throughout the study and for at least 6 months after study drug
administration (or longer, if dictated by local regulations). An acceptable
method of birth control for male participants is a double-barrier method
(e.g., male condom+either diaphragm or cervical cap with or without
spermicide).

Note: Male participants with a female partner who uses hormonal contraceptives (oral,
injectable, implants) or a hormonal (IUS) or non-hormonal IUD and male participants
who are vasectomized or otherwise incapable of fathering a child are not required to
use additional contraceptive methods.

Note 1: Sexual abstinence is considered a highly effective method only if defined as
refraining from heterosexual intercourse during the entire period of risk associated
with the study drug. The reliability of sexual abstinence needs to be evaluated in
relation to the duration of the study and the preferred and usual lifestyle of the
participant.

Note 2: A male and female condom should not be used together due to risk of breakage
or damage caused by latex friction.

NOTE: Contraceptive use by men and women should be consistent with local regulations
regarding the use of contraceptive methods for participants participating in clinical
studies if these are stricter than what is proposed in these inclusion criteria

8. Participants must agree to refrain from sperm/egg donation from start of dosing
through 6 months after the completion of study drug administration

9. Genotype (GT) 1a or 1b or GT2 or 3 chronic hepatitis C (CHC), depending on cohort,
with positive Hepatitis C virus (HCV) antibody and a positive HCV ribonucleic acid
(RNA) at screening including documentation of CHC infection for at least 6 months.
Genotype testing must occur at a screening visit. NOTE: GT1 patients are eligible for
inclusion even if they cannot be successfully subtyped unless a specific subtype is
required for a cohort

10. Screening HCV RNA viral load greater than or equal to (>=) 50,000 International Units
per milliliter (IU/mL), except for participants with compensated cirrhosis (Child Pugh
Class A) who may have HCV RNA viral load >=10^4 IU/mL

11. No prior treatment for CHC (defined as no prior exposure to any approved or
investigational drug including direct-acting antivirals, and interferon-based
treatments)

12. Fibroscan, collected within 6 months of baseline visit, with liver stiffness score
less than or equal to (<=) 12.5 kilo Pascal (kPa) to be eligible (except for
participants with cirrhosis, see below).

- participants with compensated cirrhosis must meet the Child-Pugh Class A
definition (see Appendix G) and at least one of the following criteria: i. Liver
biopsy result indicating the presence of cirrhosis (e.g., Metavir F4; Ishak >5)
or ii. Fibroscan evaluation with a liver stiffness score >12.5 kPa

13. Participant is otherwise in good health as deemed by the investigator, based on the
findings of a medical evaluation including medical history, physical examination,
laboratory tests and electrocardiogram (ECG)

14. Willing to avoid prolonged sun exposure and use of tanning devices while taking
Simeprevir (SMV) and through 4 weeks of follow up. Participant should also be advised
to use a broad-spectrum sunscreen and lip balm of at least sun protection factor >30
to help protect against potential sunburn
Minimum age
18 Years
Maximum age
70 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Pregnant, planning on becoming pregnant (during treatment and up to 6 months after the
end of treatment [EOT]), or breast-feeding female participant, or male participant
whose female partner is pregnant or planning on becoming pregnant (during treatment
and up to 6 months after the EOT)

2. Other than CHC with or without compensated cirrhosis, clinically significant
cardiovascular, respiratory, renal, gastrointestinal, hematologic, neurologic, thyroid
or any other medical illness or psychiatric disorder, as determined by the
Investigator and/or Sponsor's Medical Monitor

3. History or other clinical evidence of significant or unstable cardiac disease (e.g.,
angina, congestive heart failure, myocardial infarction, diastolic dysfunction,
significant arrhythmia, coronary heart disease, and/or clinically significant ECG
abnormalities), moderate to severe valvular disease or uncontrolled hypertension at
screening

4. Screening echocardiogram ejection fraction <55 percentage (%) or any other
echocardiographic finding suggestive of clinically relevant cardiomyopathy

5. Creatinine clearance of <60 mL/min (Cockcroft-Gault)

6. Positive test for Hepatitis A virus immunoglobulin (HAV) Immunoglobulin M (IgM),
Hepatitis B surface antigen (HBsAg), or Human Immunodeficiency Virus (HIV) Ab

7. Abnormal screening laboratory results that are considered clinically significant by
the investigator

8. History of clinical hepatic decompensation, e.g., variceal bleeding, spontaneous
bacterial peritonitis, ascites, hepatic encephalopathy or active jaundice (within last
year)

9. Any condition that, in the opinion of the investigator, would compromise the study's
objectives or the well-being of the participant or prevent the participant from
meeting the study requirements

10. Participation in an investigational drug trial or having received an investigational
vaccine within 30 days or 5 half lives (whichever is longer) prior to study medication

11. Clinically significant abnormal screening ECG findings (e.g., PR >200 msec, QRS
interval >120 millisecond (msec) or corrected QT interval (QTc) >450 msec for male
participants and >470 msec for female participants), based on an average of triplicate
ECGs. Any evidence of heart block or bundle branch block is also exclusionary

12. History or family history of abnormal ECG intervals, for example prolonged QT syndrome
(torsade de pointes) or sudden cardiac death

13. The participant has a positive prestudy drug screen, including methadone unless the
drug is prescribed by the participant's physician. The list of drugs that should be
screened for includes amphetamines, barbiturates, cocaine, opiates, phencyclidine
(PCP), and benzodiazepines

14. Laboratory abnormalities including:

- Hematocrit <0.34

- White blood cell counts <3,500/millimeter (mm)^3 (<1,000/mm^3 for participants
with compensated cirrhosis)

- Absolute neutrophil count <1,000/mm^3 (<750/mm^3 for participants with
compensated cirrhosis)

- Platelets <=120,000/mm^3 (platelets =90,000/mm^3 for participants with
compensated cirrhosis)

- Glycosylated hemoglobin (HbA1C) >55 mmol/mol

- Prothrombin time >=1.5 * upper limit of normal (ULN)

- Albumin <=32 gram per liter (g/L), bilirubin >=1.5 milligram per deciliter
(mg/dL) at screening (participants with documented Gilbert's disease allowed)

- Serum ALT concentration >=5* ULN

- CK >1.5* ULN A single repeat laboratory evaluation under appropriate conditions
(e.g., fasted, no antecedent exercise) is allowed for eligibility determination

15. Any condition possibly affecting drug absorption (e.g., gastrectomy or other
significant gastrointestinal tract surgery, such as gastroenterostomy, small bowel
resection, or active enterostomy)

16. Clinically significant blood loss or elective blood donation of significant volume
(i.e., >500 mL) within 60 days of first dose of study drug; >1 unit of plasma within 7
days of first dose of study drug

17. Evidence of clinically relevant active infection that would interfere with study
conduct or its interpretation

18. History of regular alcohol intake >10 standard drinks per week of alcohol for females
and >15 standard drinks per week for males (one unit is defined as 10 g alcohol)
within 3 months of the screening visit

19. The use of prohibited medications, including prescription, over the counter (OTC)
medications, herbal medications, inducers or inhibitors of Cytochrome P450 (CYP450)
enzymes or drug transporters (including P-gp) within 14 days prior to the first dose
of study medication is excluded, unless previously approved by the Sponsor's Medical
Monitor. NOTE: Chronic medication use is permitted so long as they are medically
necessary, deemed acceptable by the Principal Investigator and Medical Monitor, and
not Prohibited Medications (see Section 5.12)

20. Hypersensitivity to the active substances (including sulfa allergy) or to any of the
excipients of AL-335, Odalasvir (ODV) or SMV

21. Evidence on recent (within 6 months) liver ultrasound of hepatic mass or lesion
concerning for malignancy (participants with cirrhosis only)

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 2
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
31/10/2015
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
11/05/2018
Sample size
Target
Accrual to date
Final
161
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
Mauritius
State/province [1] 0 0
Phoenix
Country [2] 0 0
Moldova, Republic of
State/province [2] 0 0
Chisinau
Country [3] 0 0
New Zealand
State/province [3] 0 0
Auckland
Country [4] 0 0
New Zealand
State/province [4] 0 0
Christchurch
Country [5] 0 0
New Zealand
State/province [5] 0 0
Hamilton
Country [6] 0 0
New Zealand
State/province [6] 0 0
Havelock North
Country [7] 0 0
New Zealand
State/province [7] 0 0
Wellington
Country [8] 0 0
United Kingdom
State/province [8] 0 0
Brixton
Country [9] 0 0
United Kingdom
State/province [9] 0 0
Glasgow
Country [10] 0 0
United Kingdom
State/province [10] 0 0
Oldham

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Alios Biopharma Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to evaluate the safety and tolerability of AL-335 in combination
with odalasvir (ODV) with or without simeprevir (SMV) in participants with genotype (GT)1 or
GT2 or GT3 chronic hepatitis C (CHC) infection.
Trial website
https://clinicaltrials.gov/ct2/show/NCT02569710
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Alios Biopharma Inc. Clinical Trial
Address 0 0
Alios Biopharma Inc.
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