Chronic Hepatitis bPhase 1NCT03244085

A Study to Investigate the Safety, Efficacy and Pharmacokinetic Profile of Multiple Doses of QL-007 in Chronic Hepatitis B Patients

A Phase 1 study testing QL-007 tablet in people with Chronic Hepatitis b, run by Qilu Pharmaceutical Co., Ltd. at 1 site in New Zealand.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record

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Trial 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… Read more about this study

Who is it for?: Ages 18 to 65 years
Conditions the study is for: Chronic Hepatitis b
What is being tested?: QL-007 tablet
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 18 participants
Where: 1 siteNew Zealand
Study dates: 20 Aug 2017to 30 Dec 2018
Phase: Phase 1
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.
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.
Positive or negative for hepatitis B e antigen (HBeAg).
HBV DNA ≥ 20,000 IU/mL.
ALT levels could be normal or elevated to < 10 times upper limit of normal.
Creatinine clearance ≥ 70 mL/min.

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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
Negative serum pregnancy test for females of childbearing potential
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.
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.

Who cannot join

Patients will be excluded from the study if one or more of the following criteria are applicable:
Known co-infection with HIV, hepatitis C virus (HCV) or hepatitis D virus (HDV)
Presence of autoimmune disorders
History of liver disease other than Hepatitis B
History of Gilbert's Disease
Any sign of decompensated liver disease

Show all 30Show fewer

Known or suspected cirrhosis
Evidence of hepatocellular carcinoma
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.
Electrolyte abnormalities.
Impaired GI function or GI disease that may alter absorption of QL-007.
Ongoing GI AEs > grade 2 (eg, nausea, vomiting, or diarrhea) at screening.
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.
Alcohol or substance abuse
History of bleeding diathesis
Patients with a history of seizures, central nervous system disorders or psychiatric disability thought to be clinically significant in the opinion of the investigator.
History of clinically significant gastrointestinal, cardiovascular, endocrine, renal, ocular, pulmonary, psychiatric or neurological disease.

Trial locations and contacts

1 site in 1 country.

New Zealand1 site, 1 recruiting

P3 Research
Wellington, 6242
Richard Stubbs, Dr, 64 4 9012560, RichardS@p3research.co.nz
Recruiting

Other trials in New Zealand

About this study

Official 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

Read the detailed description

Administration of the next dose level will occur only if the preceding dose was determined to be safe and well tolerated. The decision to proceed to the next higher dose level will be made by a Safety Review Committee (SRC) based upon review of efficacy and safety data including AEs, safety laboratory results, vital signs and ECGs. PK data for up to 12 hours post-dose will also be reviewed. The review will be conducted after the last subject in a cohort completes the Day 28 visit. The planned dose levels can be modified based on the data reviewed.

Conditions: Chronic Hepatitis b
Being tested: QL-007 tablet
Medical subject headings: Hepatitis B, Chronic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

QL-007 tabletDrug
Also called QL-007
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.

Study groups in NCT03244085
Study group	Role	What they receive
100 mg BID	Experimental	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. Receives: Drug: QL-007 tablet
200 mg BID	Experimental	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. Receives: Drug: QL-007 tablet
600 mg QD	Experimental	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. Receives: Drug: QL-007 tablet

What is being measured

The primary outcome is the main question the study is designed to answer.

Incidence of Adverse Events of QL-007
Safety assessments will include adverse events, clinical safety laboratory parameters, vital signs, physical examinations, and electrocardiogram results.
Measured: From randomization up to Day 36

Secondary outcomes (9)

Peak Plasma Concentration (Cmax) of QL-007 following multiple doses
Concentrations of QL-007 in plasma will be collected on Day 1, Day 3, Day 8, Day 15, Day 22 and Day 28.
Measured: 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.
The time to Cmax (tmax) of QL-007 following multiple doses
Concentrations of QL-007 in plasma will be collected on Day 1, Day 3, Day 8, Day 15, Day 22 and Day 28.
Measured: 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.
AUC0-t (area under the plasma concentration versus time curve) of QL-007 following multiple doses
Concentrations of QL-007 in plasma will be collected on Day 1, Day 3, Day 8, Day 15, Day 22 and Day 28.
Measured: 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.
AUC0-∞ of QL-007 following multiple doses
Concentrations of QL-007 in plasma will be collected on Day 1, Day 3, Day 8, Day 15, Day 22 and Day 28.
Measured: 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.
t1/2 (terminal elimination half-life) of QL-007 following multiple doses
Concentrations of QL-007 in plasma will be collected on Day 1, Day 3, Day 8, Day 15, Day 22 and Day 28.
Measured: 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.
Vz/F(apparent volume of distribution for the terminal disposition phase) of QL-007 following multiple doses
Concentrations of QL-007 in plasma will be collected on Day 1, Day 3, Day 8, Day 15, Day 22 and Day 28.
Measured: 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.
CL/F (apparent clearance) of QL-007 following multiple doses
Concentrations of QL-007 in plasma will be collected on Day 1, Day 3, Day 8, Day 15, Day 22 and Day 28.
Measured: 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.
Change in serum HBsAg from baseline at Day 1, Day 3, Day 8, Day 15, Day 22 and Day 28
To evaluate serum levels of HBsAg, multiple blood samples will be drawn as specified in the Schedule of Assessments. Blood samples will be collected into <[specify type of tube]> tubes during screening and on Day -1; prior to investigational product administration on Days1, 3, 8, 15, 22, 28; and on the follow-up 7 ±1 days after the last dose of the investigational product.
Measured: Day 1, Day 3, Day 8, Day 15, Day 22 and Day 28
Change in serum HBV DNA from baseline at Day3, 8, 15, 22 and 28
To evaluate serum levels of HBV DNA, multiple blood samples will be drawn as specified in the Schedule of Assessments. Blood samples will be collected into <[specify type of tube]> tubes during screening and on Day -1; prior to investigational product administration on Days 1, 3, 8, 15, 22, 28; and on the follow-up 7 ±1 days after the last dose of the investigational product.
Measured: Day 1, Day 3, Day 8, Day 15, Day 22 and Day 28

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

20 Aug 201730 Dec 2018

First posted9 Aug 2017
Study start20 Aug 2017
Primary completion30 Oct 2018 (estimated)
Study completion30 Dec 2018 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Chronic Hepatitis bStudies of the same condition, open and under way.
More trials run by Qilu Pharmaceutical Co., Ltd.The sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Enrolment: 18 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03244085
Sponsor's protocol ID: QL007-002
Status last verified: Jul 2017
First submitted: 28 Jul 2017
Last updated: 16 Jul 2018
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: Undecided

Want to know more?

Each site lists its own contact. Pick the site nearest to you.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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A Study of Sequential Therapy With Daplusiran/Tomligisiran (DAP/TOM) Followed by Bepirovirsen in Participants Living With Chronic Hepatitis B (CHB)
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Study of Bepirovirsen in Participants Living With Human Immunodeficiency Virus and Chronic Hepatitis B Virus Infection (B-Focus)
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All Chronic Hepatitis b trials

Study at a glance

From the registry record, last updated by the sponsor on 16 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official 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
ClinicalTrials.gov ID: NCT03244085
Acronym / sponsor ID: QL007-002
Conditions: Chronic Hepatitis b
Phase: Phase 1
Study type: Interventional
Recruitment status: Unknown status
Enrolment: 18 participants (estimated)
Lead sponsor: Qilu Pharmaceutical Co., Ltd.Industry (pharma, biotech, devices)
Study start: 20 Aug 2017 (actual)
Primary completion: 30 Oct 2018 (estimated)
Study completion: 30 Dec 2018 (estimated)
First posted: 9 Aug 2017 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
100 mg BID	Experimental	Drug: QL-007 tabletDrug: 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.
200 mg BID	Experimental	Drug: QL-007 tabletDrug: 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.
600 mg QD	Experimental	Drug: QL-007 tabletDrug: 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.

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (13 listed)

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.
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.
Positive or negative for hepatitis B e antigen (HBeAg).
HBV DNA ≥ 20,000 IU/mL.
ALT levels could be normal or elevated to < 10 times upper limit of normal.

Key exclusion criteria (30 listed)

Patients will be excluded from the study if one or more of the following criteria are applicable:
Known co-infection with HIV, hepatitis C virus (HCV) or hepatitis D virus (HDV)
Presence of autoimmune disorders
History of liver disease other than Hepatitis B
History of Gilbert's Disease

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
QL-007 tabletAlso: QL-007Patients 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.	Drug	100 mg BID, 200 mg BID, 600 mg QD

Primary outcome

Incidence of Adverse Events of QL-007
Time frame: From randomization up to Day 36
Safety assessments will include adverse events, clinical safety laboratory parameters, vital signs, physical examinations, and electrocardiogram results.

9 secondary outcomes

Peak Plasma Concentration (Cmax) of QL-007 following multiple doses
Time frame: 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.
The time to Cmax (tmax) of QL-007 following multiple doses
Time frame: 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.
AUC0-t (area under the plasma concentration versus time curve) of QL-007 following multiple doses
Time frame: 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.
AUC0-∞ of QL-007 following multiple doses
Time frame: 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.
t1/2 (terminal elimination half-life) of QL-007 following multiple doses
Time frame: 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.
Vz/F(apparent volume of distribution for the terminal disposition phase) of QL-007 following multiple doses
Time frame: 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.
CL/F (apparent clearance) of QL-007 following multiple doses
Time frame: 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.
Change in serum HBsAg from baseline at Day 1, Day 3, Day 8, Day 15, Day 22 and Day 28
Time frame: Day 1, Day 3, Day 8, Day 15, Day 22 and Day 28
Change in serum HBV DNA from baseline at Day3, 8, 15, 22 and 28
Time frame: Day 1, Day 3, Day 8, Day 15, Day 22 and Day 28

Results and safety

Results are not available in the source record.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 16 Jul 2018.
Individual participant dataSharing planned: Undecided

Related trials for Chronic Hepatitis b

Active, not recruitingPhase 2
A Study of Sequential Therapy With Daplusiran/Tomligisiran (DAP/TOM) Followed by Bepirovirsen in Participants Living With Chronic Hepatitis B (CHB)
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

P3 Research

Wellington, New Zealand

64 4 9012560

RichardS@p3research.co.nz

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing QL-007 tablet in people with Chronic Hepatitis b, run by Qilu Pharmaceutical Co., Ltd. at 1 site in New Zealand.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 16 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in New Zealand. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of Adverse Events of QL-007 (time frame: From randomization up to Day 36). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03244085.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jul 2018.