Ignite Creation Date:
2024-05-06 @ 8:31 AM
Last Modification Date:
2024-10-26 @ 12:01 PM
Study NCT ID:
NCT02751996
Status:
COMPLETED
Last Update Posted:
2020-02-11
First Post:
2016-04-06
Brief Title:
A Study Evaluating the Safety Pharmacokinetics and Antiviral Efficacy of SB 9200 in Subjects Infected With Chronic HBV
Sponsor:
F-star Therapeutics Inc
Organization:
F-star Therapeutics Inc
Study Overview
Official Title:
A Phase 2 Open-label Randomized Two-part Multiple Dose Study Evaluating the Safety Pharmacokinetics and Antiviral Efficacy of SB 9200 in Subjects Infected With Chronic Hepatitis B Virus
Status:
COMPLETED
Status Verified Date:
2020-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
ACHIEVE
Brief Summary:
This is a Phase 2 open-labelrandomized multiple dose varied administration regimen study with 2 parts Parts A and B in Subjects Infected with Chronic Hepatitis B Virus
Detailed Description:
This is a Phase 2 open-label randomized multiple dose varied administration regimen study with 2 parts Parts A and B
Part A will utilize an ascending dose cohort design with sequential cohorts Each cohort will be evaluated by the DSMB for safety Additional cohorts may be added by the DSMB to determine doses of SB 9200 that exhibit significant antiviral response and safety
Approximately 80 subjects will be assigned sequentially to 1 of the following dosing cohorts 20 subjects per cohort and randomized in a 41 ratio activeplacebo within each cohort Randomization will be stratified so that no more than 2 HBeAg positive subjects will be assigned to receive placebo
SB 9200 25 mg or matching placebo administered qd
SB 9200 50 mg or matching placebo administered qd
SB 9200 100 mg or matching placebo administered qd
SB 9200 200 mg or matching placebo administered qd
After informed consent is obtained subjects will enter a Screening period which will last up to 28 days Once all eligibility criteria are confirmed and the subject is randomized subjects will receive the IP or placebo as a 2-week supply of capsulestablets All randomized subjects will receive the IP or matching placebo for a total of 12 weeks All subjects will then receive tenofovir 300 mg qd for an additional 12 weeks of treatment
Subjects will start the treatment period on Day 1 The PK samples will be collected on Day 1 at predose 30 minutes 1 2 4 6 and 24 hours predose the following day At Week 6 the same sampling times will be used to collect PK samples from the subjects to collect steady state PK data Subjects will return biweekly for the entire 12-week IP treatment period except when beginning IP administration when subjects will be seen weekly for safety assessments including physical examination and laboratory sample analysis of chemistry hematology and urine Sample collection for efficacy HBV DNA HBsAg HBeAg hepatitis B envelope antibody HBeAb HBV RNA and HBV resistance will be collected as indicated in the Schedule of Events A sample for genotyping will be collected at Day 1 Samples for Locarnini biomarkers and other biomarkers will also occur at Day 1 Weeks 2 4 8 12 and 14 and at the End of Study Visit Samples for cytokine levels will be collected at Day 1 Week 6 and Week 12 At Week 12 the end of IP administration all subjects will return to the clinic and be administered IP and 300 mg tenofovir Samples will be collected to explore the potential of a drug-drug interaction between SB 9200 and tenofovir All subjects will have a predose PK sample then take the last dose of IPplacebo together with their first dose of tenofovir The PK samples will then be collected for SB 9200 and tenofovir at 30 minutesand 1 2 4 6 and 24 hours Thereafter the subjects will receive only tenofovir 300 mg qd for an additional 12 weeks as 4-week supplies All subjects will return to the clinic at Weeks 13 14 16 20 and 24 Subjects will have safety assessments including symptom-directed physical examinations and safety hematology biochemistry and virological studies performed at these visits
At Week 24 all subjects will have completed the study Part A or Part B as applicable
Part B will be an open-label randomized combination therapy design consisting of multiple cohorts The study is designed to evaluate the safety tolerability and antiviral response in subjects treated for 12 weeks with a dose of SB 9200 selected from Part A that exhibits significant antiviral response and safety when administered in combination with tenofovir 300 mg qd Cohort 1 or with tenofovir 300 mg qd monotherapy alone Cohort 2 All subjects will then continue in the study for an additional 12 weeks with tenofovir alone Randomization between the 2 initial cohorts will be conducted using a 31 ratio resulting in 30 subjects being allocated to SB 9200 in combination with tenofovir Cohort 1 and 10 subjects being allocated to tenofovir monotherapy Cohort 2 No cohort can enroll more than 60 of either hepatitis e antigen negative or hepatitis e antigen positive subjects
Part B will utilize an adaptive design The first 2 cohorts of Part B may start concurrently to Part A at any time after a dose has been selected from Part A SB 9200 doses for which all subjects have not completed the initial 12 weeks monotherapy of SB 9200 from Part A and demonstrated safety of IP will not be selected to be administered in combination with tenofovir during Part B
The first 2 cohorts will randomize concurrently using a 31 ratio
Cohort 1 30 subjects will receive SB 9200 selected dose 1 from Part A administered in combination with tenofovir 300 mg qd
Cohort 2 10 subjects will receive tenofovir 300 mg qd monotherapy
Based on the results of Part A completed and ongoing cohorts and Part B first cohort up to 2 additional cohorts for which the dose of SB 9200 will be either escalated or de-escalated may be opened to enrollment
Cohort 3 30 subjects will receive SB 9200 selected dose 2 from Part A administered in combination with tenofovir 300 mg qd
Cohort 4 30 subjects will receive SB 9200 selected dose 3 from Part A administered in combination with tenofovir 300 mg qd
Subjects will be enrolled into the Screening period which will last up to 28 days Once all eligibility criteria are confirmed subjects will receive the IP as a 2-week supply of capsulestablets and tenofovir as a 4-week supply Subjects will be required to take the IP per protocol for 12 weeks Subjects will return biweekly for the entire 12-week IP treatment period except when beginning IP administration when subjects will be seen weekly for safety assessments including physical examination and laboratory sample analysis of chemistry hematology and urine Samples for Locarnini biomarkers will also occur at Day 1 Weeks 2 4 6 12 and 14 and at the End of Study Visit Sample collection for cytokine levels and other biomarkers of immune response and plasma samples will also occur at predose on Day 1 and at Weeks 612 and 24 The PK samples will be collected on Day 1 at predose 30 minutes and 1 2 4 6 and 24 hours predose the following day At Week 12 the same sampling times will be used to collect PK samples from the subjects to collect steady state PK data Sample collection for population PK analysis will also be collected before IP administration at Weeks 4 and 8 Urinary PK will be collected on Day 1 and Week 12 predose 6 hours and 24 hours predose the following day
At Week 12 all subjects will be administered tenofovir 300 mg qd for an additional 12 weeks as 4-week supplies All subjects will return to the clinic at Weeks 13 14 16 20 and 24 Subjects will have safety assessments including symptom-directed physical examinations and safety hematology biochemistry and virological studies performed at these visits
Safety reporting for each subject in each cohort will continue after the subject first consents to participate in the study through the 24 week duration of the study or through the Extension Period until 30 days after the last dose is administered
At Week 24 all subjects will have completed the study Part A or Part B as applicable
Extension Period
Any subject who completes Part A or Part B may be eligible to take part in a 12-month Extension Period Before any study-related procedures are performed the subjects will have all study procedures explained to them including information regarding the nature of the study and subjects must sign an informed consentassent form During the Extension Period subjects will receive tenofovir and return for visits every 3 months with laboratory tests of liver function and virological efficacy including HBsAg HBeAg HBeAb and HBV DNA No further study-related testing will be performed Subjects who undergo full termination from the study during Part A or Part B will not be eligible to enroll into the extension study
Safety reporting for each subject in each cohort will continue after the subject first consents to participate in the study through the 24-week duration of the study or through the Extension Period until 30 days after the last dose is administered
Part A will utilize an ascending dose cohort design with sequential cohorts Each cohort will be evaluated by the DSMB for safety Additional cohorts may be added by the DSMB to determine doses of SB 9200 that exhibit significant antiviral response and safety
Approximately 80 subjects will be assigned sequentially to 1 of the following dosing cohorts 20 subjects per cohort and randomized in a 41 ratio activeplacebo within each cohort Randomization will be stratified so that no more than 2 HBeAg positive subjects will be assigned to receive placebo
SB 9200 25 mg or matching placebo administered qd
SB 9200 50 mg or matching placebo administered qd
SB 9200 100 mg or matching placebo administered qd
SB 9200 200 mg or matching placebo administered qd
After informed consent is obtained subjects will enter a Screening period which will last up to 28 days Once all eligibility criteria are confirmed and the subject is randomized subjects will receive the IP or placebo as a 2-week supply of capsulestablets All randomized subjects will receive the IP or matching placebo for a total of 12 weeks All subjects will then receive tenofovir 300 mg qd for an additional 12 weeks of treatment
Subjects will start the treatment period on Day 1 The PK samples will be collected on Day 1 at predose 30 minutes 1 2 4 6 and 24 hours predose the following day At Week 6 the same sampling times will be used to collect PK samples from the subjects to collect steady state PK data Subjects will return biweekly for the entire 12-week IP treatment period except when beginning IP administration when subjects will be seen weekly for safety assessments including physical examination and laboratory sample analysis of chemistry hematology and urine Sample collection for efficacy HBV DNA HBsAg HBeAg hepatitis B envelope antibody HBeAb HBV RNA and HBV resistance will be collected as indicated in the Schedule of Events A sample for genotyping will be collected at Day 1 Samples for Locarnini biomarkers and other biomarkers will also occur at Day 1 Weeks 2 4 8 12 and 14 and at the End of Study Visit Samples for cytokine levels will be collected at Day 1 Week 6 and Week 12 At Week 12 the end of IP administration all subjects will return to the clinic and be administered IP and 300 mg tenofovir Samples will be collected to explore the potential of a drug-drug interaction between SB 9200 and tenofovir All subjects will have a predose PK sample then take the last dose of IPplacebo together with their first dose of tenofovir The PK samples will then be collected for SB 9200 and tenofovir at 30 minutesand 1 2 4 6 and 24 hours Thereafter the subjects will receive only tenofovir 300 mg qd for an additional 12 weeks as 4-week supplies All subjects will return to the clinic at Weeks 13 14 16 20 and 24 Subjects will have safety assessments including symptom-directed physical examinations and safety hematology biochemistry and virological studies performed at these visits
At Week 24 all subjects will have completed the study Part A or Part B as applicable
Part B will be an open-label randomized combination therapy design consisting of multiple cohorts The study is designed to evaluate the safety tolerability and antiviral response in subjects treated for 12 weeks with a dose of SB 9200 selected from Part A that exhibits significant antiviral response and safety when administered in combination with tenofovir 300 mg qd Cohort 1 or with tenofovir 300 mg qd monotherapy alone Cohort 2 All subjects will then continue in the study for an additional 12 weeks with tenofovir alone Randomization between the 2 initial cohorts will be conducted using a 31 ratio resulting in 30 subjects being allocated to SB 9200 in combination with tenofovir Cohort 1 and 10 subjects being allocated to tenofovir monotherapy Cohort 2 No cohort can enroll more than 60 of either hepatitis e antigen negative or hepatitis e antigen positive subjects
Part B will utilize an adaptive design The first 2 cohorts of Part B may start concurrently to Part A at any time after a dose has been selected from Part A SB 9200 doses for which all subjects have not completed the initial 12 weeks monotherapy of SB 9200 from Part A and demonstrated safety of IP will not be selected to be administered in combination with tenofovir during Part B
The first 2 cohorts will randomize concurrently using a 31 ratio
Cohort 1 30 subjects will receive SB 9200 selected dose 1 from Part A administered in combination with tenofovir 300 mg qd
Cohort 2 10 subjects will receive tenofovir 300 mg qd monotherapy
Based on the results of Part A completed and ongoing cohorts and Part B first cohort up to 2 additional cohorts for which the dose of SB 9200 will be either escalated or de-escalated may be opened to enrollment
Cohort 3 30 subjects will receive SB 9200 selected dose 2 from Part A administered in combination with tenofovir 300 mg qd
Cohort 4 30 subjects will receive SB 9200 selected dose 3 from Part A administered in combination with tenofovir 300 mg qd
Subjects will be enrolled into the Screening period which will last up to 28 days Once all eligibility criteria are confirmed subjects will receive the IP as a 2-week supply of capsulestablets and tenofovir as a 4-week supply Subjects will be required to take the IP per protocol for 12 weeks Subjects will return biweekly for the entire 12-week IP treatment period except when beginning IP administration when subjects will be seen weekly for safety assessments including physical examination and laboratory sample analysis of chemistry hematology and urine Samples for Locarnini biomarkers will also occur at Day 1 Weeks 2 4 6 12 and 14 and at the End of Study Visit Sample collection for cytokine levels and other biomarkers of immune response and plasma samples will also occur at predose on Day 1 and at Weeks 612 and 24 The PK samples will be collected on Day 1 at predose 30 minutes and 1 2 4 6 and 24 hours predose the following day At Week 12 the same sampling times will be used to collect PK samples from the subjects to collect steady state PK data Sample collection for population PK analysis will also be collected before IP administration at Weeks 4 and 8 Urinary PK will be collected on Day 1 and Week 12 predose 6 hours and 24 hours predose the following day
At Week 12 all subjects will be administered tenofovir 300 mg qd for an additional 12 weeks as 4-week supplies All subjects will return to the clinic at Weeks 13 14 16 20 and 24 Subjects will have safety assessments including symptom-directed physical examinations and safety hematology biochemistry and virological studies performed at these visits
Safety reporting for each subject in each cohort will continue after the subject first consents to participate in the study through the 24 week duration of the study or through the Extension Period until 30 days after the last dose is administered
At Week 24 all subjects will have completed the study Part A or Part B as applicable
Extension Period
Any subject who completes Part A or Part B may be eligible to take part in a 12-month Extension Period Before any study-related procedures are performed the subjects will have all study procedures explained to them including information regarding the nature of the study and subjects must sign an informed consentassent form During the Extension Period subjects will receive tenofovir and return for visits every 3 months with laboratory tests of liver function and virological efficacy including HBsAg HBeAg HBeAb and HBV DNA No further study-related testing will be performed Subjects who undergo full termination from the study during Part A or Part B will not be eligible to enroll into the extension study
Safety reporting for each subject in each cohort will continue after the subject first consents to participate in the study through the 24-week duration of the study or through the Extension Period until 30 days after the last dose is administered
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None