E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Inactive Chronic Hepatitis B (CHB) |
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E.1.1.1 | Medical condition in easily understood language |
Inactive Chronic Hepatitis B (CHB) |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10008910 |
E.1.2 | Term | Chronic hepatitis B |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess virologic response to HepTcell in treatment-naïve patients with inactive CHB
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E.2.2 | Secondary objectives of the trial |
•To assess cellular immune response of HepTcell in treatment-naïve patients with inactive CHB •To assess the safety of HepTcell in treatment-naïve patients with inactive CHB
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Able and willing to provide informed consent. 2. Men and women 18 to 65 years of age, inclusive 3. Body Mass Index (BMI) 18.0 to 34.9 kg/m2, inclusive 4. Inactive, treatment-naïve CHB with documented HBsAg positivity for at least 12 months before Day 1 (The history of HBsAg positivity may be reduced to 6 months provided HBV anti-core IgM antibodies are negative) 5. qHBsAg ≥ 10 IU/mL but ≤ 200 IU/mL in the 12 months prior to screening or from informed consent to randomization If a patient has more than one qHBsAg value within 12 months and prior to randomization, the patient will be deemed eligible if any one measurement is within the eligible range. 6. AST, ALT, INR, albumin, total bilirubin (excluding patients with Gilbert Syndrome, who will only be eligible for study participation if total bilirubin is ≤ 3.0 mg/dL) and direct bilirubin within normal limits at screening. Note: ALT and AST elevations up to 1.5 x ULN are allowed if evidence of hepatic steatosis, defined as one of the following criteria: 1) fatty liver on ultrasound, or other imaging modality or Fibroscan controlled attenuation parameter (CAP) ≥ 260 dB/m. To qualify under these conditions, HBV DNA must be <2,000 IU/mL, and there must be no history or signs of liver disease other than fatty liver and HBV. 7. Negative drug screen at screening unless prescribed by a medical practitioner for medical use (NB, recreational and prescription cannabis is allowed) 8. For women of childbearing potential (women who are not permanently sterile [documented hysterectomy, bilateral tubal ligation, salpingectomy, or oophorectomy] or postmenopausal [12 months with no menses without an alternative medical cause]): a. Negative pregnancy test on Day 1 b. Willingness to practice a highly effective method of birth control with low user dependency from screening through one menstrual cycle after the last dose of study medication, which include: i. Abstinence ii. Sex only with persons of the same sex iii. Monogamous relationship with vasectomized partner iv. Intrauterine device v. Combined estrogen and progestogen containing hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal) vi. Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable or implantable) vii. Intrauterine hormone-releasing system Patients who practice true abstinence or who exclusively have same sex partners need not use contraception, provided it is in line with their preferred and usual lifestyle. Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. Should any such patient stop practicing abstinence, they must use contraception as described above. 9.For men with sexual partners of childbearing potential, as defined above: a. Abstinence b. History of vasectomy or surgical sterilization c. Monogamous relationship with a postmenopausal or surgically sterilized partner d. Willingness to practice a highly effective method of contraception, as defined above, for 90 days after the last dose of study medication and to refrain from sperm donation for this time The same criteria pertaining to abstinence and withdrawal methods in women of childbearing potential (Inclusion Criterion 8) apply to men with sexual partners of childbearing potential 10. Willingness to comply with all aspects of the study through the entire study period Patients who fail to meet Inclusion Criteria 5 and/or 6 and otherwise meet the requirements for study participation will be permitted one additional blood draw during the same screening period to requalify. Patients who screen fail for other Inclusion Criteria may undergo rescreening at the discretion of the Investigator and Medical Monitor. |
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E.4 | Principal exclusion criteria |
1. Pregnant or lactating women 2. Positive hepatitis B e antigen (HBeAg) at screening 3. History of a hepatitis B flare or 1-log increase in HBV DNA or HBsAg in the prior 6 months 4. Prior or current history of active or untreated human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis delta virus (HDV) 5. Acute COVID-19, a positive test result for SARS-CoV2 infection, or exposure within 14 days to an individual with acute COVID-19 6. Febrile illness (temperature ≥ 38.0 °C) within the past 14 days 7. Prior or current history of any underlying liver disease not related to HBV (NB, steatosis, as documented by imaging or Fibroscan CAP, is permitted if ALT and AST are <1.5 x ULN and HBV DNA <2,000 IU/mL and there is no history or signs of liver disease other than fatty liver and HBV) 8. Fibroscan > 8.5 kPA at screening, or history of hepatic fibrosis or cirrhosis (NB, a Fibroscan is not required if an examination is performed within 12 months before screening, or a liver biopsy was performed within 2 years before Screening and no fibrosis [F1 or greater] was identified.) 9. History of cirrhosis or signs of hepatic decompensation, including but not limited to variceal bleeding, ascites, or hepatic encephalopathy 10. White blood cell count < 3,500/μL, neutrophils < 1,000/μL, hemoglobin < 11 g/dL, or platelets < 125,000/μL Note: Individuals of African descent with a white blood cell count <3,500/ μL will not be excluded for this reason if white blood cell count is ≥ 2,500/μL, provided that the neutrophil count is ≥ 1,000/μL and there is no other identified cause of leukopenia. 11. Prior treatment with an approved or investigational agent for HBV 12. History of conditions associated with immunocompromise 13. History of conditions associated with altered immune response, such as anaphylaxis, angioedema, or autoimmune disease 14. Treatments known to affect the immune system, such as corticosteroids (other than topical or inhaled preparations), alkylating drugs, antimetabolites, cytotoxic drugs, radiation, immune-modulating biologics, allergy injections, immunoglobulins, interferons or other immunomodulating therapies, within 30 days of screening 15. Uncontrolled diabetes mellitus, defined as Hemoglobin A1C (HbA1C) ≥ 10% at screening 16. Receipt of live-attenuated replicating vaccines within 30 days or receipt of any other licensed or authorized vaccines (including vaccines intended to prevent COVID-19) within 14 days prior to Day 1 17. Change in any chronically administered medication or treatment within 14 days of screening or inability to maintain these medications at the same dose through Day 169 (NB, patients chronically using aspirin, non-steroidal anti-inflammatory agents, antacids, vitamins, probiotics, and over-the-counter medications will maintain their level of intake throughout the study) 18. Malignancy within 3 years of screening, excluding non-melanoma skin cancers and carcinoma in situ cervical cancer (NB, patients who have undergone prior screening for HCC by imaging or alpha-fetoprotein levels will have negative test results) 19. Untreated alcohol or drug abuse 20. Planned elective surgery or hospitalization during the study period 21. Participation in a prior trial involving HepTcell or FP-02.2 22. Known allergy to any of the ingredients in HepTcell 23. Receipt of any investigational drug or treatment within 30 days before Day 1 or planned use during the study period 24. Any medical, psychiatric, or social condition or occupational or other responsibility that in the judgment of the Investigator would interfere with or serve as a contraindication to protocol adherence, assessment of safety (including reactogenicity), or a patient's ability to give informed consent Patients who are excluded by Exclusion Criterion 10 but otherwise meet the requirements for study participation will be permitted one additional blood draw to requalify. Patients who screen fail for other Exclusion Criteria may undergo rescreening at the discretion of the Investigator and Medical Monitor. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The proportion of patients achieving virologic response, defined as a 1.0-log reduction in qHBsAg or serologic clearance of HBsAg, Baseline to Day 169 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
•Proportion of patients achieving serologic clearance of HBsAg on Day 169 •Proportion of patients achieving serologic clearance of HBV DNA on Day 169 •Changes in qHBsAg, HBV DNA, HBcrAg, and pg-RNA levels, Baseline to Days 85 and 169 •Change in IFN-γ frequency by ELISpot in PBMCs, Baseline to Days 85 and 169
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 8 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
Thailand |
United Kingdom |
United States |
Germany |
Italy |
Spain |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 27 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 27 |