Study of the Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Characteristics of PA1010 in HBV Patients

NCT05019040 | Completed Phase 1

• 1 other identifier: PA1010-102
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 4

Brief Summary

The primary objective of this study is to evaluate the safety, tolerability, pharmacokinetic and pharmacodynamic characteristics of multiple ascending dose (MAD) of PA1010 tablets in Chinese adults with Chronic Hepatitis B.

Conditions

Chronic HBV Infection

Outcome Measures

Primary Outcomes (11)

• Evaluation the change from baseline in Serum HBV DNA in patients

  The primary efficacy endpoint is the change from baseline in Serum HBV DNA in patients on day 28 in all patients. The safety and tolerance are also observed in all treatment groups.

  28 days

• Evaluation the rate of change from Baseline in Serum HBV DNA

  Rate of change from Baseline in Serum HBV DNA

  28 days

• Evaluation the change from Baseline in Serum HBsAg

  Change from Baseline in Serum HBsAg

  28 days

• Evaluation the change from Baseline in Serum ALT

  Change from Baseline in Serum ALT

  28 days

• Number of subjects experiencing adverse events (AEs)

  An adverse event (AE) is defined as any untoward medical occurrence in a clinical study subject administered a medicinal product which does not necessarily have a causal relationship with this treatment.

  28 days

• Pharmacokinetics of single dose of PA1010-Cmax

  Blood samples will be collected serially, and the concentrations of PA1010 in plasma samples are determined by liquid chromatography/mass spectrometry/mass spectrometry (LC/MS/MS), followed by the calculation of pharmacokinetic parameter Maximum Observed Plasma Concentration (Cmax)

  28 days

• Pharmacokinetics of single dose of PA1010-Tmax

  Blood samples will be collected serially, and the concentrations of PA1010 in plasma samples are determined by liquid chromatography/mass spectrometry/mass spectrometry (LC/MS/MS), followed by the calculation of pharmacokinetic parameter Time to Reach Maximum Observed Plasma Concentration (Tmax)

  28 days

• Pharmacokinetics of single dose of PA1010-AUC

  Blood samples will be collected serially, and the concentrations of PA1010 in plasma samples are determined by liquid chromatography/mass spectrometry/mass spectrometry (LC/MS/MS), followed by the calculation of pharmacokinetic parameter Area Under the Plasma Concentration-Time Curve (AUC)

  28 days

• ECG parameter-QTc interval、PR interval、QRS duration

  A 12 lead electrocardiogram (ECG) will be recorded using an ECG machine that automatically measures QTc interval、PR interval、QRS duration

  28 days

• Number of new abnormal signs with clinical significance

  Physical examination records include: skin, lymph nodes, head and neck (including thyroid), nervous system examination (including but not limited to speech, cranial nerves, motor ability, tendon reflex, sensation, ataxia), chest (heart, lung), abdomen (liver, gallbladder, spleen, kidney), etc.

  28 days

• Body temperature, blood pressure, pulse, respiratory rate

  Vital signs body temperature, blood pressure, pulse, respiratory rate

  28 days

Secondary Outcomes (4)

• Pharmacokinetics of single dose of PA1010-T1/2

  28 days

• Pharmacokinetics of single dose of PA1010-Vz/F

  28 days

• Pharmacokinetics of single dose of PA1010-CL/F

  28 days

• Pharmacokinetics of single dose of PA1010-λz

  28 days

Study Arms (3)

PA1010 5 mg

EXPERIMENTAL

Twelve subjects will be randomly assigned at a 3: 1 ratio to receive either 5 mg of PA1010 tablets or 300 mg of TDF tablets, once daily for 28 days.

Drug: PA1010

PA1010 10 mg

EXPERIMENTAL

Twelve subjects will be randomly assigned at a 3: 1 ratio to receive either 10 mg of PA1010 tablets or 300 mg of TDF tablets, once daily for 28 days.

Drug: PA1010

PA1010 20 mg

EXPERIMENTAL

Twelve subjects will be randomly assigned at a 3: 1 ratio to receive either 20 mg of PA1010 tablets or 300 mg of TDF tablets, once daily for 28 days.

Drug: PA1010

Interventions

PA1010 DRUG

TDF as control

PA1010 10 mg; PA1010 20 mg; PA1010 5 mg

Eligibility Criteria

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

You may qualify if:

• Sign on the informed consent form to indicate willingness to participate in this study;
• Male or female CHB patients aged between 18 and 65 (including upper and lower limits), and should meet the following requirements:
• One of the following conditions:
• records show that hepatitis B surface antigen (HBsAg) is positive and / or hepatitis B virus deoxyribonucleic acid (HBV DNA) is positive for more than 6 months;
• the serum immunoglobulin M (IgM) antibody of HBcAg is negative, and HBsAg is positive;
• HBsAg positive and / or HBV DNA positive, and liver biopsy results show chronic hepatitis B (including previous biopsy results);
• Have not used nucleoside (acid) analogues within 6 months before the first administration, or have received effective, nucleoside(acid) analogues or interferon treatment, but discontinuation of the drug for more than 6 months;
• For HBeAg positive patients: HBV DNA \> 2 × 105 IU/mL； For HBeAg negative patients: HBV DNA \> 2 × 104 IU/mL；
• × Upper limit of normal value (ULN) ≤ alanine aminotransferase (ALT) ≤ 10 × ULN； Serum total bile Hemoglobin ≤ 2 × ULN； Creatinine clearance (clcr) \> 70 ml / min (using Cockcroft Gault formula law);
• Urine protein is negative or 1+ (it is necessary to add 24 hours of urine protein quantification when 1+. If within the normal range, selected);
• No major disease history, and the physical examination, vital signs, 12 lead electrocardiogram (ECG) and laboratory examination results are normal during the screening period , although they exceed the normal reference value range, they are judged by the investigator to be of no clinical significance;
• Subjects are forbidden to donate blood or use drugs within 30 days after the last dose;
• During the study period (from signing the informed consent to the last follow-up) and within 6 months after the last dose, sperm donation and egg donation are prohibited, and there is no possibility of pregnancy (or sexual partner pregnancy), childbirth and lactation, at least one of the following conditions is met:
• Menopausal women who have menopause for more than 12 months or undergo sterilization (such as hysterectomy, ligation of both fallopian tubes or bilateral ovariectomy);
• For premenopausal women, pregnancy tests in the screening period and baseline period are negative, and they are willing to take more than one effective contraceptive method from the screening period to 6 months after the last dose, including intrauterine device, tubal ligation, double barrier method (condom / vaginal diaphragm + spermicide) and male partner vas deferens ligation, but excluding oral contraceptives;

You may not qualify if:

• Potential subjects who meet any of the following criteria will be excluded from the study:
• There are any medical conditions that the investigator believes may increase the risk of subjects participating in the study (especially the history of esophageal or gastrointestinal ulcer), may interfere with the absorption, distribution, metabolism or excretion of drugs, or may weaken the compliance with the study protocol;
• Patients with liver diseases other than hepatitis B, including but not limited to patients with chronic alcoholic hepatitis, drug-induced liver injury, autoimmune liver disease, known Gilbert syndrome and other hereditary liver diseases;
• Any history or current signs of liver decompensation (ascites, hepatic encephalopathy or esophageal and gastric varices bleeding) at any time before or at the time of screening, child Pugh grade B or C;
• Those who have received solid organ or bone marrow transplantation;
• History of severe kidney disease (judged by the researcher) or current signs;
• Serious bone diseases (such as osteomalacia, chronic osteomyelitis, osteogenesis imperfecta, chondrosis) or multiple bone diseases fold;
• Liver malignant tumor or other untreated malignant tumor was diagnosed before the first administration ;
• Have received any other study drug within 90 days before the first dose;
• Those who have used other nucleosides (acids) or interferons within 6 months before the first administration;
• Before the first administration, stop the prescription drug or over-the-counter drug that other researchers believe will affect the evaluation results of this study less than 14 days or 5 half lives of the drug (whichever is longer);
• Blood donation or massive blood loss (\>400 ml) within 3 months before the first administration of the study drug;
• Major surgery or trauma within 6 months before the first administration;
• Take drinks or food containing grapefruit, pomegranate, papaya, grape and carambola within 14 days before the first administration, or disagree to avoid taking any drinks or food containing grapefruit, pomegranate, papaya, grape and carambola every day during the test;
• Have taken any food or drink rich in caffeine and xanthine (coffee, tea, coke, chocolate, seafood, animal liver, etc.) within 48 hours before the first administration, or do not agree to avoid taking any food or drink rich in caffeine and xanthine (coffee, tea, coke, chocolate, seafood, animal liver, etc.) every day during the test;

Sponsors & Collaborators

• Zhejiang Palo Alto Pharmaceuticals, Inc.: lead

Study Sites (4)

Beijing Tsinghua Changgung Hospital affiliated to Tsinghua

Beijing, Beijing Municipality, China

Location

The Second Affiliated Hospital of Chongqing Medical University

Chongqing, Chongqing Municipality, 400010, China

Location

Southern Hospital of Southern Medical University

Guangzhou, Guangdong, China

Location

The First Affiliated Hospital of Medical College of Zhejiang University

Hangzhou, Zhejiang, China

Location

Study Officials

• Lai Wei, MD

  Beijing Tsinghua Changgung Hospital affiliated to Tsinghua University

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: August 17, 2021
• First Posted: August 24, 2021
• Study Start: September 17, 2021
• Primary Completion: November 15, 2022
• Study Completion: November 18, 2022
• Last Updated: January 31, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (4)