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

NCT03244085 | Unknown Phase 1 DMC

• 1 other identifier: QL007-002
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

Chronic Hepatitis b

Outcome Measures

Primary Outcomes (1)

• Incidence of Adverse Events of QL-007

  Safety assessments will include adverse events, clinical safety laboratory parameters, vital signs, physical examinations, and electrocardiogram results.

  From randomization up to Day 36

Secondary Outcomes (9)

• Peak Plasma Concentration (Cmax) of QL-007 following multiple doses

  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

  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

  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

  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

  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.

Study Arms (3)

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.

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.

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.

Drug: QL-007 tablet

Interventions

QL-007 tablet DRUG

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.

Also known as: QL-007

100 mg BID; 200 mg BID; 600 mg QD

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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
• 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;

Sponsors & Collaborators

• Qilu Pharmaceutical Co., Ltd.: lead

Study Sites (1)

P3 Research

Wellington, 6242, New Zealand

RECRUITING

MeSH Terms

Conditions

Hepatitis B, Chronic

Condition Hierarchy (Ancestors)

Hepatitis B; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 28, 2017
• First Posted: August 9, 2017
• Study Start: August 20, 2017
• Primary Completion: October 30, 2018
• Study Completion: December 30, 2018
• Last Updated: July 16, 2018

Record last verified: 2017-07

Locations

NZ (1)