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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/NCT03244085




Registration number
NCT03244085
Ethics application status
Date submitted
28/07/2017
Date registered
9/08/2017
Date last updated
16/07/2018

Titles & IDs
Public title
A Study to Investigate the Safety, Efficacy and Pharmacokinetic Profile of Multiple Doses of QL-007 in Chronic Hepatitis B Patients
Scientific title
An Open-Label Phase 1b Study to Evaluate the Dose-Related Safety, Efficacy, and Pharmacokinetic Profile of Different Doses of QL-007 in Chronic Hepatitis B Patients
Secondary ID [1] 0 0
QL007-002
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Hepatitis b 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 - QL-007 tablet

Experimental: 100 mg BID - Drug: QL-007 tablet; Tablet QL-007 will be administered orally daily (100 mg two times a day) over the 28 days under fasted state. Patients fast for 2h before administration and 1h after administration.

Experimental: 200 mg BID - Drug: QL-007 tablet; Tablet QL-007 will be administered orally daily (200 mg two times a day) over the 28 days under fasted state. Patients fast for 2h before administration and 1h after administration.

Experimental: 600 mg QD - Drug: QL-007 tablet; Tablet QL-007 will be administered orally daily (600 mg once a day) over the 28 days under fasted state. Patients fast for 2h before administration and 1h after administration.


Treatment: Drugs: QL-007 tablet
Patients will be enrolled in 1 of 3 cohorts (6 patients per cohort): QL 007 200 mg/day (100 mg BID), or QL 007 400 mg/day (200 mg/BID), or QL 007 600 mg QD. QL 007 will be administered orally daily over the 28 days under fasted state. Patients fast for 2h before administration and 1h after administration.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence of Adverse Events of QL-007
Timepoint [1] 0 0
From randomization up to Day 36
Secondary outcome [1] 0 0
Peak Plasma Concentration (Cmax) of QL-007 following multiple doses
Timepoint [1] 0 0
On Day 1, Day 3, Day 8, Day 15, Day 22 and Day 28, samples will be collected pre-dose; on Day 1 and 28, samples will also be collected at 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h and 12h post dose.
Secondary outcome [2] 0 0
The time to Cmax (tmax) of QL-007 following multiple doses
Timepoint [2] 0 0
On Day 1, Day 3, Day 8, Day 15, Day 22 and Day 28, samples will be collected pre-dose; on Day 1 and 28, samples will also be collected at 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h and 12h post dose.
Secondary outcome [3] 0 0
AUC0-t (area under the plasma concentration versus time curve) of QL-007 following multiple doses
Timepoint [3] 0 0
On Days 1, 3, 8, 15, 22 and 28, samples will be collected pre-dose; on Day 1 and 28, samples will also be collected at 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h and 12h post dose.
Secondary outcome [4] 0 0
AUC0-8 of QL-007 following multiple doses
Timepoint [4] 0 0
On Day 1, Day 3, Day 8, Day 15, Day 22 and Day 28, samples will be collected pre-dose; on Day 1 and 28, samples will also be collected at 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h and 12h post dose.
Secondary outcome [5] 0 0
t1/2 (terminal elimination half-life) of QL-007 following multiple doses
Timepoint [5] 0 0
On Day 1, Day 3, Day 8, Day 15, Day 22 and Day 28, samples will be collected pre-dose; on Day 1 and 28, samples will also be collected at 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h and 12h post dose.
Secondary outcome [6] 0 0
Vz/F(apparent volume of distribution for the terminal disposition phase) of QL-007 following multiple doses
Timepoint [6] 0 0
On Day 1, Day 3, Day 8, Day 15, Day 22 and Day 28, samples will be collected pre-dose; on Day 1 and 28, samples will also be collected at 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h and 12h post dose.
Secondary outcome [7] 0 0
CL/F (apparent clearance) of QL-007 following multiple doses
Timepoint [7] 0 0
On Day 1, Day 3, Day 8, Day 15, Day 22 and Day 28, samples will be collected pre-dose; on Day 1 and 28, samples will also be collected at 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h and 12h post dose.
Secondary outcome [8] 0 0
Change in serum HBsAg from baseline at Day 1, Day 3, Day 8, Day 15, Day 22 and Day 28
Timepoint [8] 0 0
Day 1, Day 3, Day 8, Day 15, Day 22 and Day 28
Secondary outcome [9] 0 0
Change in serum HBV DNA from baseline at Day3, 8, 15, 22 and 28
Timepoint [9] 0 0
Day 1, Day 3, Day 8, Day 15, Day 22 and Day 28

Eligibility
Key inclusion criteria
1. Adult (age 18-65 years inclusive) males or females with chronic HBV (positive for
serum hepatitis B surface antigen (HBsAg) or HBV DNA for = 6 months) prior to
baseline.

2. Anti-HBV treatment-naive adults; adults who have taken oral anti-HBV nucleoside
therapy with the last dose = 4 weeks prior to screening are also eligible.

3. Positive or negative for hepatitis B e antigen (HBeAg).

4. HBV DNA = 20,000 IU/mL.

5. ALT levels could be normal or elevated to < 10 times upper limit of normal.

6. Creatinine clearance = 70 mL/min.

7. The following laboratory criteria have been met:

- Absolute neutrophil count (ANC) = 1.5 x 109/L

- Hemoglobin (Hgb) = 8 g/dL

- Platelets = 75 x 109/L

8. Negative serum pregnancy test for females of childbearing potential

9. For men and women who are not postmenopausal (ie, = 12 months of non-therapy-induced
amenorrhea, confirmed by follicle stimulating hormone (FSH), if not on hormone
replacement) or surgically sterile (vasectomy in males or absence of ovaries and/or
uterus or tubal ligation in females) agreement to remain abstinent or use a highly
effective method of contraception during the treatment period and at least through
week 12 after last dose.

10. Participants must have signed an ICF indicating that they understand the purpose of
and procedures required for the study and are willing to participate in the study and
comply with the study procedures and restrictions.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria

Patients will be excluded from the study if one or more of the following criteria are
applicable:

1. Known co-infection with HIV, hepatitis C virus (HCV) or hepatitis D virus (HDV)

2. Presence of autoimmune disorders

3. History of liver disease other than Hepatitis B

4. History of Gilbert's Disease

5. Any sign of decompensated liver disease

6. Known or suspected cirrhosis

7. Evidence of hepatocellular carcinoma

8. Patient has clinically significant, uncontrolled heart disease and/or recent cardiac
event (within 6 months), such as:

- unstable angina within 6 months prior to screening;

- myocardial infarction within 6 months prior to screening;

- history of documented congestive heart failure (New York Heart Association
functional classification III-IV);

- uncontrolled hypertension defined by a systolic blood pressure (SBP) = 160 mm Hg
and/or diastolic blood pressure (DBP) = 100 mm Hg, with or without
antihypertensive medication;

- initiation or adjustment of antihypertensive medication(s) is allowed prior to
screening;

- ventricular arrhythmias; supraventricular and nodal arrhythmias not controlled
with medication;

- other cardiac arrhythmia not controlled with medication;

- corrected QTc > 450 msec using Fridericia correction on the screening ECG.

9. Electrolyte abnormalities.

10. Impaired GI function or GI disease that may alter absorption of QL-007.

11. Ongoing GI AEs > grade 2 (eg, nausea, vomiting, or diarrhea) at screening.

12. Receiving medications that meet one of the following criteria and that cannot be
discontinued = 1 week prior to the start of treatment QL 007:

- Medication with a known risk of prolonging the QT interval or inducing Torsades
de Pointes (see Appendix 3; please refer to
https://crediblemeds.org/pdftemp/pdf/CombinedList.pdf

- Moderate or strong inhibitors or strong inducers of CYP3A (please refer to
http://medicine.iupui.edu/flockhart/table.htm or
http://www.druginteractioninfo.org)

- Unstable or increasing doses of corticosteroids

- Enzyme-inducing anticonvulsive agents

- Herbal supplements.

13. Alcohol or substance abuse

14. History of bleeding diathesis

15. Patients with a history of seizures, central nervous system disorders or psychiatric
disability thought to be clinically significant in the opinion of the investigator.

16. History of clinically significant gastrointestinal, cardiovascular, endocrine, renal,
ocular, pulmonary, psychiatric or neurological disease.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised 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
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Unknown status
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
20/08/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/12/2018
Actual
Sample size
Target
18
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
New Zealand
State/province [1] 0 0
Wellington

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Qilu Pharmaceutical Co., Ltd.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a nonrandomized, open-label, no-control, dose-escalation Phase 1b trial in 18
patients with chronic HBV infection to determine the safety, preliminary efficacy, and
pharmacokinetics (PK) of QL-007 after administration over 28 days of multiple oral doses in a
fasted state at the following planned dose levels: 200 mg/day (100 mg two times a day (BID)),
400 mg/day (200 mg BID), then 600 mg once daily (QD), with 6 patients for each cohort.
Trial website
https://clinicaltrials.gov/ct2/show/NCT03244085
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
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/NCT03244085