Clinical Trials List
Protocol NumberALN-HBV-001
NCT Number(ClinicalTrials.gov Identfier)NCT02826018
2016-09-01 - 2018-11-30
Others
Terminated5
ICD-10B18.1
Chronic viral hepatitis B without delta-agent
ICD-9070.32
Viral hepatitis B without mention of hepatic coma, chronic, without mention of hepatitis delta
A Phase 1/2, Randomized, Single-Blind, Placebo-Controlled, Single-Ascending and Multiple-Ascending Dose, Safety, Tolerability, Pharmacokinetics, and Antiviral Efficacy Study of Subcutaneously Administered ALN-HBV in Healthy Adult Subjects and Non-cirrhotic Patients with Chronic Hepatitis B Virus (HBV) Infection
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Trial Applicant
PPD DEVELOPMENT (HK) LIMITED
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Sponsor
Alnylam Pharmaceuticals, Inc.
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Hung-Yao Chen Digestive System Department
- 蘇文邦 Digestive System Department
- 陳昇弘 Digestive System Department
- Hsueh-Chou Lai Digestive System Department
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
Audit
None
Co-Principal Investigator
- Ming-Lun Yeh Digestive System Department
- Jee-Fu Huang Digestive System Department
- Ming-Lung Yu Digestive System Department
- Chia-Yen Dai Digestive System Department
- 黃駿逸 Digestive System Department
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- Chun-Jen Liu Digestive System Department
- 蘇東弘 Digestive System Department
- 楊宏志 Digestive System Department
- Chien-Hung Chen Digestive System Department
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Audit
None
Condition/Disease
Chronic Hepatitis B Virus (HBV) Infection
Objectives
Primary
• To evaluate the safety and tolerability of single or multiple doses of ALN-HBV in healthy adult subjects and non-cirrhotic patients with chronic HBV infection when administered as monotherapy or concomitantly with the anti-HBV nucleoside (NUC), entecavir, or the anti-HBV nucleotide (NUC), tenofovir
Secondary
• To characterize the pharmacokinetics (PK) of ALN-HBV in healthy adult subjects and non-cirrhotic patients with chronic HBV infection
• To assess the antiviral efficacy of ALN-HBV in non-cirrhotic patients with chronic HBV infection who are receiving anti-HBV NUC treatment (Parts B and C) as measured by changes Hepatitis B surface antigen (HBsAg) levels
Exploratory (HBV Patients; Parts B and C only)
• To assess the effect of ALN-HBV on other markers of HBV infection including but not limited to detection of HBV DNA, Hepatitis B surface antibody (HBsAb), and Hepatitis B extracellular antibody (HBeAb)
• To evaluate additional parameters which may interrogate the mechanism of the anti-HBV activity of ALN-HBV in study subjects and/or evaluate the impact of observed antiviral activity on the immune control of HBV
Test Drug
ALN-HBV
Active Ingredient
ALN-66810(double stranded oligonucleotide covalently linked to a ligand containing 3 GalNAc residues
Dosage Form
Vial
Dosage
200mg / ml
Endpoints
Primary (Parts A, B, and C; All subjects)
• Incidence of adverse events
• Clinical laboratory test results
Secondary
Parts A, B, and C (All Subjects)
Pharmacokinetic parameters of ALN-HBV and possible metabolites (may include, but not be limited to, maximum plasma concentration, time to reach maximum plasma concentration, area under the plasma concentration versus time curve, apparent terminal elimination half-life, fraction eliminated in the urine, and renal clearance).
Parts B and C only (HBV Patients)
Change in the levels of HBsAg in blood
Exploratory (Parts B and C only; HBV patients)
Change in the levels of HBV DNA in blood
Evaluation of other markers of HBV infection
• Incidence of adverse events
• Clinical laboratory test results
Secondary
Parts A, B, and C (All Subjects)
Pharmacokinetic parameters of ALN-HBV and possible metabolites (may include, but not be limited to, maximum plasma concentration, time to reach maximum plasma concentration, area under the plasma concentration versus time curve, apparent terminal elimination half-life, fraction eliminated in the urine, and renal clearance).
Parts B and C only (HBV Patients)
Change in the levels of HBsAg in blood
Exploratory (Parts B and C only; HBV patients)
Change in the levels of HBV DNA in blood
Evaluation of other markers of HBV infection
Inclution Criteria
1. Main inclusion criteria:
Each patient must meet all of the following inclusion criteria to be eligible for enrollment in the study.
1. Age 18 (The subject participating in this study in Taiwan must be over 20 years of age.) to 65 years, inclusive
2. 12-lead electrocardiogram (ECG) within normal limits or with no clinically significant abnormalities at screening and Day -1 in the opinion of the Investigator.
3. Women of child-bearing potential must have a negative pregnancy test, cannot be breast feeding, and must be willing to use a highly effective method of contraception 14 days before first dose, throughout study participation, and for 90 days after last dose administration.
4. Agrees not to donate blood during the duration of the study
5. Willing to comply with the study requirements and to provide written informed consent.
6. Nonsmokers and non-users of nicotine or light smokers and users of nicotine (defined as the equivalent of 10 cigarettes per day) for at least 90 days before screening
7. Body mass index (BMI) ≥18.0 kg/m2 and ≤32 kg/m2 as assessed at screening.
8. A negative test for HBeAg in blood at screening (at the recommendation of the SRC subjects who are HBeAg positive at screening may be allowed to enroll in an optional cohort(s) in Parts B and/or C).
9. Chronic HBV infection as evidenced by a screening HBsAg level > 500 IU/mL.
10. A history of treatment with only one HBV polymerase inhibitor, entecavir or tenofovir.
11. Taking entecavir or tenofovir for at least 12 months prior to screening without an interruption of 7 or more consecutive days over this time period.
12. Screening HBV DNA below the lower limit of quantitation (100 IU/mL in the last 6 months. Only a single HBV DNA measure that is ≥LLOQ but ≤100 IU/mL in the last 6 months is permitted provided that the subsequent HBV DNA level is
Each patient must meet all of the following inclusion criteria to be eligible for enrollment in the study.
1. Age 18 (The subject participating in this study in Taiwan must be over 20 years of age.) to 65 years, inclusive
2. 12-lead electrocardiogram (ECG) within normal limits or with no clinically significant abnormalities at screening and Day -1 in the opinion of the Investigator.
3. Women of child-bearing potential must have a negative pregnancy test, cannot be breast feeding, and must be willing to use a highly effective method of contraception 14 days before first dose, throughout study participation, and for 90 days after last dose administration.
4. Agrees not to donate blood during the duration of the study
5. Willing to comply with the study requirements and to provide written informed consent.
6. Nonsmokers and non-users of nicotine or light smokers and users of nicotine (defined as the equivalent of 10 cigarettes per day) for at least 90 days before screening
7. Body mass index (BMI) ≥18.0 kg/m2 and ≤32 kg/m2 as assessed at screening.
8. A negative test for HBeAg in blood at screening (at the recommendation of the SRC subjects who are HBeAg positive at screening may be allowed to enroll in an optional cohort(s) in Parts B and/or C).
9. Chronic HBV infection as evidenced by a screening HBsAg level > 500 IU/mL.
10. A history of treatment with only one HBV polymerase inhibitor, entecavir or tenofovir.
11. Taking entecavir or tenofovir for at least 12 months prior to screening without an interruption of 7 or more consecutive days over this time period.
12. Screening HBV DNA below the lower limit of quantitation (
Exclusion Criteria
Each patient must not meet any of the following exclusion criteria to be eligible for enrollment in the study.
1. Any uncontrolled or serious disease, or any medical or surgical condition, that may either interfere with participation in the clinical study, and/or put the subject at significant risk (according to Investigator’s judgment) if he/she participates in the clinical study, with the exception of chronic HBV infection for patients in Parts B and C.
2. An underlying known disease, or surgical or medical condition that, in the opinion of the Investigator, might interfere with interpretation of the clinical study results, with the exception of chronic HBV infection for patients in Parts B and C.
3. Active serious mental illness or psychiatric disorder, including but not limited to schizophrenia, bipolar disorder, or severe depression requiring current pharmacological intervention.
4. Clinically significant illness within 7 days before the first dose of study drug.
5. Systolic blood pressure >140 mmHg and a diastolic blood pressure of >90 mmHg after 10 minutes supine rest at screening.
6. Indirect bilirubin > 1.5 × ULN and direct bilirubin > ULN at screening.
7. Any clinical safety laboratory result considered clinically significant and unacceptable by the Investigator at screening.
8. Received an investigational agent within 90 days before the first dose of study drug or are active in the follow-up phase of another clinical study involving interventional treatment.
9. Clinical laboratory evidence of active infection with human immunodeficiency virus (HIV) infection, hepatitis A virus (HAV), or hepatitis C virus (HCV) infection and/or a history of delta virus hepatitis.
10. Consume more than 14 (female) or 21 (male) units of alcohol per week (unit: 1 glass of wine [125 mL] = 1 measure of spirits = ½ pint of beer).
11. History or clinical evidence of alcohol abuse, within the 12 months before screening. Alcohol abuse is defined as regular weekly intake of more than 21 units for males and 14 units for females.
12. History or clinical evidence of drug abuse, within the 12 months before screening. Drug abuse is defined as compulsive, repetitive, and/or chronic use of drugs or other substances with or without problems related to their use and/or where stopping or a reduction in dose will lead to withdrawal symptoms.
13. Known hypersensitivity or contraindication to any medication or history of allergic reaction to an oligonucleotide or N-acetylgalactosamine (GalNAc).
14. Positive screen for drugs of abuse without a ready explanation, i.e., a permitted prescription medication or a short-term use of an over-the-counter medication, and which use is considered consistent with the result of the urine test.
15. History of intolerance to SC injection or relevant abdominal scarring (surgical, burns, etc.).
16. Legal incapacity or limited legal capacity at screening.
17. Any conditions which, in the opinion of the Investigator, would make the subject unsuitable for enrollment or could interfere with the subject’s participation in or completion of the study.
18. Donated more than 500 mL of blood within 90 days before the first dose of study drug.
19. Woman who are pregnant or breastfeeding.
20. Estimated glomerular filtration rate (using MDRD equation) < 60 mL/min/1.73 m2 at screening.
21. History of chronic liver disease from any cause other than chronic HBV infection.
22. History of cirrhosis.
23. History of hepatic decompensation, including ascites, hepatic encephalopathy and/or esophageal or gastric varices.
24. Screening ALT level >3×ULN.
25. Serum albumin level < lower limit of normal at screening.
26. Platelet count ≤100,000 per microliter at screening.
27. Absolute neutrophil count (ANC) <1500 cells/µL at screening.
28. International normalized ratio (INR) or prothrombin time (PT) above the upper limit of the normal reference range (as per the local laboratory reference range) at screening.
1. Any uncontrolled or serious disease, or any medical or surgical condition, that may either interfere with participation in the clinical study, and/or put the subject at significant risk (according to Investigator’s judgment) if he/she participates in the clinical study, with the exception of chronic HBV infection for patients in Parts B and C.
2. An underlying known disease, or surgical or medical condition that, in the opinion of the Investigator, might interfere with interpretation of the clinical study results, with the exception of chronic HBV infection for patients in Parts B and C.
3. Active serious mental illness or psychiatric disorder, including but not limited to schizophrenia, bipolar disorder, or severe depression requiring current pharmacological intervention.
4. Clinically significant illness within 7 days before the first dose of study drug.
5. Systolic blood pressure >140 mmHg and a diastolic blood pressure of >90 mmHg after 10 minutes supine rest at screening.
6. Indirect bilirubin > 1.5 × ULN and direct bilirubin > ULN at screening.
7. Any clinical safety laboratory result considered clinically significant and unacceptable by the Investigator at screening.
8. Received an investigational agent within 90 days before the first dose of study drug or are active in the follow-up phase of another clinical study involving interventional treatment.
9. Clinical laboratory evidence of active infection with human immunodeficiency virus (HIV) infection, hepatitis A virus (HAV), or hepatitis C virus (HCV) infection and/or a history of delta virus hepatitis.
10. Consume more than 14 (female) or 21 (male) units of alcohol per week (unit: 1 glass of wine [125 mL] = 1 measure of spirits = ½ pint of beer).
11. History or clinical evidence of alcohol abuse, within the 12 months before screening. Alcohol abuse is defined as regular weekly intake of more than 21 units for males and 14 units for females.
12. History or clinical evidence of drug abuse, within the 12 months before screening. Drug abuse is defined as compulsive, repetitive, and/or chronic use of drugs or other substances with or without problems related to their use and/or where stopping or a reduction in dose will lead to withdrawal symptoms.
13. Known hypersensitivity or contraindication to any medication or history of allergic reaction to an oligonucleotide or N-acetylgalactosamine (GalNAc).
14. Positive screen for drugs of abuse without a ready explanation, i.e., a permitted prescription medication or a short-term use of an over-the-counter medication, and which use is considered consistent with the result of the urine test.
15. History of intolerance to SC injection or relevant abdominal scarring (surgical, burns, etc.).
16. Legal incapacity or limited legal capacity at screening.
17. Any conditions which, in the opinion of the Investigator, would make the subject unsuitable for enrollment or could interfere with the subject’s participation in or completion of the study.
18. Donated more than 500 mL of blood within 90 days before the first dose of study drug.
19. Woman who are pregnant or breastfeeding.
20. Estimated glomerular filtration rate (using MDRD equation) < 60 mL/min/1.73 m2 at screening.
21. History of chronic liver disease from any cause other than chronic HBV infection.
22. History of cirrhosis.
23. History of hepatic decompensation, including ascites, hepatic encephalopathy and/or esophageal or gastric varices.
24. Screening ALT level >3×ULN.
25. Serum albumin level < lower limit of normal at screening.
26. Platelet count ≤100,000 per microliter at screening.
27. Absolute neutrophil count (ANC) <1500 cells/µL at screening.
28. International normalized ratio (INR) or prothrombin time (PT) above the upper limit of the normal reference range (as per the local laboratory reference range) at screening.
The Estimated Number of Participants
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Taiwan
41 participants
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Global
112 participants
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