Hepatitis BPhase 2ACHIEVENCT02751996
A Study Evaluating the Safety, Pharmacokinetics, and Antiviral Efficacy of SB 9200 in Subjects Infected With Chronic HBV
A Phase 2 study testing SB 9200 and Tenofovir in people with Hepatitis B and Hepatitis, Viral, run by F-star Therapeutics, Inc. at 17 sites in 4 countries.
Trial summary
This is a Phase 2, open-label,randomized, multiple dose, varied administration regimen study with 2 parts (Parts A and B) in Subjects Infected with Chronic Hepatitis B Virus Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Hepatitis B, Hepatitis, Viral
- What is being tested?
- SB 9200 and Tenofovir
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 17 sitesin 4 countries
- Study dates
- May 2016to 10 Feb 2020
- Phase
- Phase 2
- 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Documented evidence of chronic HBV infection (eg, HBsAg positive for at least 6 months or HBV DNA positive for at least 6 months). In the absence of documented evidence of HBsAg or HBV DNA, the subject must be HBsAg positive, and anti-HBc (IgM) negative at Screening.
- Not on any antiviral medications for at least 6 months. If a subject is HBeAg negative, they will be eligible if they have not received antiviral medications for at least 3 months. Antiviral medications include lamivudine, telbivudine, adefovir, tenofovir, entecavir, IFN therapies of any type, and all other medications with potential antiviral activity.
- HBV DNA > 2000 IU/mL for HBeAg-negative subjects and > 20000 IU/mL for HBeAg-positive subjects at Screening
- ALT > ULN, but < 5 x the ULN and ≤ 200 U/L
- Ultrasound, computed tomography (CT) scan, or magnetic resonance imaging (MRI) within 3 months of randomization date with no evidence of hepatocellular carcinoma
- Must be willing and able to comply with all study requirements
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- Negative urine or serum pregnancy test (for women of childbearing potential [WOCBP]) documented within the 24-hour period prior to the first dose of test drug. If the urine pregnancy test is positive, a follow-up serum test is required for confirmation. Additionally, all fertile males with partners of childbearing age and females must be using reliable contraception during the study and for 3 months after treatment completion. All fertile males must also refrain from sperm donation while on IP and for 3 months after completion of IP.
- Must have the ability to understand and sign a written ICF; consent must be obtained prior to initiation of study procedures
- Subjects who meet all of the following inclusion criteria may be eligible to be enrolled into the Extension Period:
- Signed informed consent form
- Subject was randomized in Part A or Part B
Who cannot join
- Subjects who meet any of the following exclusion criteria are not to be enrolled in this study:
- Any prior liver biopsy evidence of metavir F3 or F4 disease
- Any history of decompensation of liver disease including history of ascites, encephalopathy, or varices
- Evidence of cirrhosis as defined by Fibroscan at the Screening Visit of ≥ 8 kilopascals (kPa) or both a Fibrotest ≥ 0.65 and AST:platelet ratio index (APRI) ≥ 1.0 (subjects will not be excluded if only 1 of the Fibrotest or APRI result is higher than allowed) or have had evidence of Metavir F3-F4 on liver biopsy at any time.
- Laboratory parameters not within defined thresholds: white blood cells (WBC) < 4000 cells/µL, (SI unit < 4.0 × 109/L), hemoglobin (HgB) < 12 g/dL (SI unit < 120 g/L) for females, < 13 g/dL (SI unit < 130 g/L) for males, platelets < 130,000 per µL, (SI unit < 130 × 109/L), albumin < 3.5 g/dL,(SI unit < 35 g/L), international normalized ratio (INR) > 1.5, total bilirubin > 1.2 mg/dL, (SI unit > 20.52 µmol/L), or alpha-fetoprotein (AFP) > 50 ng/mL (SI unit > 180.25 nmol/L). Subjects with an elevated indirect bilirubin and known Gilbert's disease can be included if direct bilirubin is within normal limits. Subjects with an AFP > 50 ng/mL but ˂ 500 ng/mL can be included if computed tomography (CT) scan or magnetic resonance imaging (MRI) performed within 3 months shows no evidence of hepatocellular carcinoma
- Creatinine > 1.2 mg/dL, (SI unit > 106.08 µmol/L), creatinine clearance < 50 mL/min, (SI unit < 0.83 L/s/m2)
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- Co-infection with hepatitis C virus (HCV), human immunodeficiency virus (HIV), or hepatitis D virus
- Evidence or history of hepatocellular carcinoma
- Malignancy within 5 years prior to Screening, with the exception of specific cancers that are cured by surgical resection (basal cell skin cancer, etc). Subjects under evaluation for possible malignancy are not eligible.
- Significant cardiovascular, pulmonary, or neurological disease
- Received solid organ or bone marrow transplant
- Received within 3 months of Screening or expected to receive prolonged therapy with immunomodulators (eg, corticosteroids) or biologics (eg, monoclonal antibody, IFN)
- Subjects currently taking medication(s) that are transported through organic anion transporting polypeptide 1 (OATP1) including, but not limited to, atazanavir, rifampin, cyclosporine, eltrombopag, gemfibrozil, lopinavir/ritonavir, and saquinavir
- Use of another investigational agent within 3 months of Screening
- Current alcohol or substance abuse judged by the Investigator to potentially interfere with compliance
- Females who are pregnant or may wish to become pregnant during the study
- If the Investigator believes the prospective subject will not be able to comply with the requirements of the protocol and complete the study
- Any medical condition, in the opinion of the Investigator, that could interfere with evaluation of the study objectives or safety of the subjects
- Exclusion Criteria for Extension Period Subjects who meet any of the following exclusion criteria are not to be enrolled into the Extension Period:
- Any condition, comorbidity, or laboratory abnormality that, based on the package insert of tenofovir or in the opinion of the Investigator, excludes the subject
- Subjects who were withdrawn from Part A or Part B due to an AE or serious adverse event (SAE) related to the use of tenofovir
- Participation in any other interventional study
- Subject fully terminated from Part A or Part B
Trial locations and contacts
17 sites in 4 countries.
17 sites in 4 countries
South Korea6 sites
Spring Bank Pharma Research site
Busan
Spring Pharma Research Site
Chuncheon, Gangwon-do
Spring Bank Pharma Research Site
Daegu
Spring Bank Pharma Research site
Goyang-si
Spring Bank Pharma Research site
Seoul
Spring Bank Pharma Research site
Yangsan, Gyeongsangnam-do
Canada5 sites
Spring Bank Pharma Research site
Calgary, Alberta
Spring Bank Pharma Research Site
London, Ontario
Spring Bank Pharma Research site
Toronto, Ontario
Spring Bank Pharma Research site
Vancouver, British Columbia
Spring Bank Pharma Research site
Vaughan, Ontario
Taiwan4 sites
Spring Bank Pharma Research Site
Chia-Yi City
Spring Bank Pharma Research Site
New Taipei City
Spring Bank Pharma Research Site
Taipei
Spring Bank Pharma Research Site
Taoyuan County
Hong Kong2 sites
Spring Bank Pharma Research site
Hong Kong
Spring Bank Pharma Research site
Shatin
About this study
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
This is a Phase 2, open-label,randomized, multiple dose, varied administration regimen study with 2 parts (Parts A and B) in Subjects Infected with Chronic Hepatitis B Virus
Read the 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 4:1 ratio (active:placebo) 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 capsules/tablets. 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 IP/placebo together with their first dose of tenofovir. The PK samples will then be collected for SB 9200 and tenofovir at 30 minutes,and 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 3:1 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 3:1 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 capsules/tablets 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 6,12 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 consent/assent 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.
- Conditions
- Hepatitis B, Hepatitis, Viral
- Being tested
- SB 9200, Placebo, Tenofovir
- Keywords
- Chronic Hepatitis, HBV, Double blind
- Medical subject headings
- Hepatitis B, Hepatitis, Hepatitis, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SB 9200Drug
Also called SB9200
SB 9200
PlaceboDrug
TenofovirDrug
| Study group | Role | What they receive |
|---|---|---|
| Part A Cohort 1: 25mg SB 9200 | Active comparator | Part A Cohort 1: 25mg SB 9200. After 12 weeks of SB 9200 this medication will be stopped. From weeks 12 - 24 patients will be given 12 weeks of Tenofovir (current standard of care) Receives: Drug: SB 9200 |
| Part A Cohort 1: 25mg Placebo | Placebo comparator | Part A Cohort 1: 25mg Placebo. After 12 weeks of Placebo this medication will be stopped. From weeks 12 - 24 patients will be given 12 weeks of Tenofovir (current standard of care) Receives: Drug: Placebo |
| Part A Cohort 2: 50mg SB 9200 | Active comparator | Part A Cohort 2: 50mg SB 9200. After 12 weeks of SB 9200 this medication will be stopped. From weeks 12 - 24 patients will be given 12 weeks of Tenofovir (current standard of care) Receives: Drug: SB 9200 |
| Part A Cohort 2: 50mg Placebo | Placebo comparator | Part A Cohort 2: 50mg Placebo. After 12 weeks of Placebo this medication will be stopped. From weeks 12 - 24 patients will be given 12 weeks of Tenofovir (current standard of care) Receives: Drug: Placebo |
| Part A Cohort 3: 100mg SB 9200 | Active comparator | Part A Cohort 3: 100mg SB 9200. After 12 weeks of SB 9200 this medication will be stopped. From weeks 12 - 24 patients will be given 12 weeks of Tenofovir (current standard of care) Receives: Drug: SB 9200 |
| Part A Cohort 3: 100mg Placebo | Placebo comparator | Part A Cohort 3: 100mg Placebo. After 12 weeks of Placebo this medication will be stopped. From weeks 12 - 24 patients will be given 12 weeks of Tenofovir (current standard of care) Receives: Drug: Placebo |
| Part A Cohort 4: 200mg SB 9200 | Active comparator | Part A Cohort 4: 200mg SB 9200. After 12 weeks of SB 9200 this medication will be stopped. From weeks 12 - 24 patients will be given 12 weeks of Tenofovir (current standard of care) Receives: Drug: SB 9200 |
| Part A Cohort 4: 200mg Placebo | Placebo comparator | Part A Cohort 4: 200mg Placebo. After 12 weeks of Placebo this medication will be stopped. From weeks 12 - 24 patients will be given 12 weeks of Tenofovir (current standard of care) Receives: Drug: Placebo |
| Part B: SB 9200 with tenofovir | Active comparator | Part B: SB 9200 selected dose from Part A administered in combination with tenofovir 300 mg qd. After 12 weeks of SB 9200 this medication will be stopped. From weeks 12 - 24 patients will be given 12 weeks of Tenofovir (current standard of care) Receives: Drug: SB 9200 |
| Part B: Tenofovir 300 mg | Active comparator | Part B: Tenofovir 300 mg qd monotherapy. After 12 weeks of SB 9200 this medication will be stopped. From weeks 12 - 24 patients will be given 12 weeks of Tenofovir (current standard of care) Receives: Drug: Tenofovir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part A: Proportion of subjects reporting an adverse event (AE) and HBV DNA decline
The primary endpoint for safety and efficacy in Part A is the proportion of subjects reporting an adverse event (AE) or experiencing a clinically significant AE or laboratory abnormality from baseline (Randomisation) to end of SB 9200 treatment (12 weeks) and change from baseline to Week 12 in Log10 HBV DNA.
Measured: 12 weeks
Part B: Proportion of subjects reporting an adverse event (AE) and hepatitis B surface antigen decline
The primary endpoints for safety and efficacy in Part B is the proportion of subjects reporting an adverse event (AE) or experiencing a clinically significant AE or laboratory abnormality from baseline (Randomisation) to end of SB 9200 treatment (12 weeks) and the proportion of subjects with hepatitis B surface antigen decline (12 weeks)
Measured: 12 weeks
Secondary outcomes (8)
Maximum observed plasma SB 9200 plasma concentration (Cmax) and determination of pharmacokineticPK parameters for SB 9200 and, Rp -SB 9000, and Sp SB 9000 (Parts A and B)
Measured: 0 - 24 hours
Change in serum HBV DNA, HBsAg, and HBV RNA at 2, 4, 8, 12, 14, and 24 weeks (Part A)
Measured: 2, 4, 8, 12, 14, and 24 weeks
Change in serum HBV DNA, HBsAg, and HBV RNA at 2, 4, 6, 12, 14, and 24 weeks (Part B)
Measured: 2, 4, 6, 12, 14, and 24 weeks
Change in HBeAg in log10 IU/mL from Baseline to Weeks 2, 4, 8, 12, 14, and 24 (Part A)
Measured: Weeks 2, 4, 8, 12, 14, and 24 weeks
Change in HBeAg in log10 IU/mL from Baseline to Weeks 2, 4, 6, 12, 14, and 24 (Part B)
Measured: 2, 4, 6, 12, 14, and 24 weeks
Proportion of subjects with HBeAg or HBsAg loss and seroconversion at Weeks 2, 4, 8, 12, 14, and 24 (Part A)
Measured: 2, 4, 8, 12, 14, and 24 weeks
Proportion of subjects with HBeAg or HBsAg loss and seroconversion at Weeks 2, 4, 6, 12, 14, and 24 (Part B)
Measured: 2, 4, 6, 12, 14, and 24 weeks
Proportion of subjects with HBsAg ≥ 1 log10 reduction from Baseline to Week 12 (Part B)
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Apr 2016 (estimated)
- Study startMay 2016
- Primary completion10 Feb 2020
- Study completion10 Feb 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatitis BStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- F-star Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Chelsea Macfarlane, Study director, SBP Sr. Director of Clinical Operations
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02751996
- Sponsor's protocol ID
- SBP-9200-HBV-201
- Acronym
- ACHIEVE
- Status last verified
- Feb 2020
- First submitted
- 6 Apr 2016
- Last updated
- 11 Feb 2020
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No: No plan to share data at this stage
Study at a glance
From the registry record, last updated by the sponsor on 11 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02751996
- Acronym / sponsor ID
- ACHIEVE / SBP-9200-HBV-201
- Conditions
- Hepatitis B, Hepatitis, Viral
- Keywords
- Chronic Hepatitis, HBV, Double blind
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- F-star Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- May 2016
- Primary completion
- 10 Feb 2020 (actual)
- Study completion
- 10 Feb 2020 (actual)
- First posted
- 26 Apr 2016 (estimated)
- 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.
This is a Phase 2, open-label,randomized, 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 4:1 ratio (active:placebo) 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 capsules/tablets. 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 IP/placebo together with their first dose of tenofovir. The PK samples will then be collected for SB 9200 and tenofovir at 30 minutes,and 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 3:1 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 3:1 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 capsules/tablets 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 6,12 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 consent/assent 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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 10
| Arm | Type | Receives |
|---|---|---|
| Part A Cohort 1: 25mg SB 9200 | Active comparator | Drug: SB 9200Part A Cohort 1: 25mg SB 9200. After 12 weeks of SB 9200 this medication will be stopped. From weeks 12 - 24 patients will be given 12 weeks of Tenofovir (current standard of care) |
| Part A Cohort 1: 25mg Placebo | Placebo comparator | Drug: PlaceboPart A Cohort 1: 25mg Placebo. After 12 weeks of Placebo this medication will be stopped. From weeks 12 - 24 patients will be given 12 weeks of Tenofovir (current standard of care) |
| Part A Cohort 2: 50mg SB 9200 | Active comparator | Drug: SB 9200Part A Cohort 2: 50mg SB 9200. After 12 weeks of SB 9200 this medication will be stopped. From weeks 12 - 24 patients will be given 12 weeks of Tenofovir (current standard of care) |
| Part A Cohort 2: 50mg Placebo | Placebo comparator | Drug: PlaceboPart A Cohort 2: 50mg Placebo. After 12 weeks of Placebo this medication will be stopped. From weeks 12 - 24 patients will be given 12 weeks of Tenofovir (current standard of care) |
| Part A Cohort 3: 100mg SB 9200 | Active comparator | Drug: SB 9200Part A Cohort 3: 100mg SB 9200. After 12 weeks of SB 9200 this medication will be stopped. From weeks 12 - 24 patients will be given 12 weeks of Tenofovir (current standard of care) |
| Part A Cohort 3: 100mg Placebo | Placebo comparator | Drug: PlaceboPart A Cohort 3: 100mg Placebo. After 12 weeks of Placebo this medication will be stopped. From weeks 12 - 24 patients will be given 12 weeks of Tenofovir (current standard of care) |
| Part A Cohort 4: 200mg SB 9200 | Active comparator | Drug: SB 9200Part A Cohort 4: 200mg SB 9200. After 12 weeks of SB 9200 this medication will be stopped. From weeks 12 - 24 patients will be given 12 weeks of Tenofovir (current standard of care) |
| Part A Cohort 4: 200mg Placebo | Placebo comparator | Drug: PlaceboPart A Cohort 4: 200mg Placebo. After 12 weeks of Placebo this medication will be stopped. From weeks 12 - 24 patients will be given 12 weeks of Tenofovir (current standard of care) |
| Part B: SB 9200 with tenofovir | Active comparator | Drug: SB 9200Part B: SB 9200 selected dose from Part A administered in combination with tenofovir 300 mg qd. After 12 weeks of SB 9200 this medication will be stopped. From weeks 12 - 24 patients will be given 12 weeks of Tenofovir (current standard of care) |
| Part B: Tenofovir 300 mg | Active comparator | Drug: TenofovirPart B: Tenofovir 300 mg qd monotherapy. After 12 weeks of SB 9200 this medication will be stopped. From weeks 12 - 24 patients will be given 12 weeks of Tenofovir (current standard of care) |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Documented evidence of chronic HBV infection (eg, HBsAg positive for at least 6 months or HBV DNA positive for at least 6 months). In the absence of documented evidence of HBsAg or HBV DNA, the subject must be HBsAg positive, and anti-HBc (IgM) negative at Screening.
- Not on any antiviral medications for at least 6 months. If a subject is HBeAg negative, they will be eligible if they have not received antiviral medications for at least 3 months. Antiviral medications include lamivudine, telbivudine, adefovir, tenofovir, entecavir, IFN therapies of any type, and all other medications with potential antiviral activity.
- HBV DNA > 2000 IU/mL for HBeAg-negative subjects and > 20000 IU/mL for HBeAg-positive subjects at Screening
- ALT > ULN, but < 5 x the ULN and ≤ 200 U/L
- Ultrasound, computed tomography (CT) scan, or magnetic resonance imaging (MRI) within 3 months of randomization date with no evidence of hepatocellular carcinoma
Key exclusion criteria (23 listed)
- Subjects who meet any of the following exclusion criteria are not to be enrolled in this study:
- Any prior liver biopsy evidence of metavir F3 or F4 disease
- Any history of decompensation of liver disease including history of ascites, encephalopathy, or varices
- Evidence of cirrhosis as defined by Fibroscan at the Screening Visit of ≥ 8 kilopascals (kPa) or both a Fibrotest ≥ 0.65 and AST:platelet ratio index (APRI) ≥ 1.0 (subjects will not be excluded if only 1 of the Fibrotest or APRI result is higher than allowed) or have had evidence of Metavir F3-F4 on liver biopsy at any time.
- Laboratory parameters not within defined thresholds: white blood cells (WBC) < 4000 cells/µL, (SI unit < 4.0 × 109/L), hemoglobin (HgB) < 12 g/dL (SI unit < 120 g/L) for females, < 13 g/dL (SI unit < 130 g/L) for males, platelets < 130,000 per µL, (SI unit < 130 × 109/L), albumin < 3.5 g/dL,(SI unit < 35 g/L), international normalized ratio (INR) > 1.5, total bilirubin > 1.2 mg/dL, (SI unit > 20.52 µmol/L), or alpha-fetoprotein (AFP) > 50 ng/mL (SI unit > 180.25 nmol/L). Subjects with an elevated indirect bilirubin and known Gilbert's disease can be included if direct bilirubin is within normal limits. Subjects with an AFP > 50 ng/mL but ˂ 500 ng/mL can be included if computed tomography (CT) scan or magnetic resonance imaging (MRI) performed within 3 months shows no evidence of hepatocellular carcinoma
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 |
|---|---|---|
| SB 9200Also: SB9200SB 9200 | Drug | Part A Cohort 1: 25mg SB 9200, Part A Cohort 2: 50mg SB 9200, Part A Cohort 3: 100mg SB 9200, Part A Cohort 4: 200mg SB 9200, Part B: SB 9200 with tenofovir |
| Placebo | Drug | Part A Cohort 1: 25mg Placebo, Part A Cohort 2: 50mg Placebo, Part A Cohort 3: 100mg Placebo, Part A Cohort 4: 200mg Placebo |
| Tenofovir | Drug | Part B: Tenofovir 300 mg |
Primary outcome
Part A: Proportion of subjects reporting an adverse event (AE) and HBV DNA decline
Time frame: 12 weeks
The primary endpoint for safety and efficacy in Part A is the proportion of subjects reporting an adverse event (AE) or experiencing a clinically significant AE or laboratory abnormality from baseline (Randomisation) to end of SB 9200 treatment (12 weeks) and change from baseline to Week 12 in Log10 HBV DNA.
Part B: Proportion of subjects reporting an adverse event (AE) and hepatitis B surface antigen decline
Time frame: 12 weeks
The primary endpoints for safety and efficacy in Part B is the proportion of subjects reporting an adverse event (AE) or experiencing a clinically significant AE or laboratory abnormality from baseline (Randomisation) to end of SB 9200 treatment (12 weeks) and the proportion of subjects with hepatitis B surface antigen decline (12 weeks)
8 secondary outcomes
Maximum observed plasma SB 9200 plasma concentration (Cmax) and determination of pharmacokineticPK parameters for SB 9200 and, Rp -SB 9000, and Sp SB 9000 (Parts A and B)
Time frame: 0 - 24 hours
Change in serum HBV DNA, HBsAg, and HBV RNA at 2, 4, 8, 12, 14, and 24 weeks (Part A)
Time frame: 2, 4, 8, 12, 14, and 24 weeks
Change in serum HBV DNA, HBsAg, and HBV RNA at 2, 4, 6, 12, 14, and 24 weeks (Part B)
Time frame: 2, 4, 6, 12, 14, and 24 weeks
Change in HBeAg in log10 IU/mL from Baseline to Weeks 2, 4, 8, 12, 14, and 24 (Part A)
Time frame: Weeks 2, 4, 8, 12, 14, and 24 weeks
Change in HBeAg in log10 IU/mL from Baseline to Weeks 2, 4, 6, 12, 14, and 24 (Part B)
Time frame: 2, 4, 6, 12, 14, and 24 weeks
Proportion of subjects with HBeAg or HBsAg loss and seroconversion at Weeks 2, 4, 8, 12, 14, and 24 (Part A)
Time frame: 2, 4, 8, 12, 14, and 24 weeks
Proportion of subjects with HBeAg or HBsAg loss and seroconversion at Weeks 2, 4, 6, 12, 14, and 24 (Part B)
Time frame: 2, 4, 6, 12, 14, and 24 weeks
Proportion of subjects with HBsAg ≥ 1 log10 reduction from Baseline to Week 12 (Part B)
Time frame: 12 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Feb 2020.
- Individual participant dataSharing planned: No. No plan to share data at this stage
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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.
Chelsea Macfarlane study director
SBP Sr. Director of Clinical Operations
17 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing SB 9200 and Tenofovir in people with Hepatitis B and Hepatitis, Viral, run by F-star Therapeutics, Inc. at 17 sites in 4 countries.
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 11 inclusion and 23 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: finished, as of the sponsor's last update on 11 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in South Korea, Canada, Taiwan, Hong Kong. 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Part A: Proportion of subjects reporting an adverse event (AE) and HBV DNA decline (time frame: 12 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 11 Feb 2020.