HepTcell (Adjuvanted FP-02.2) in patients with inactive CHB
Research type
Research Study
Full title
Phase 2, Double-blind, Randomized, Placebo-controlled Study of HepTcell (Adjuvanted FP-02.2) as an Immunotherapeutic Vaccine in Treatment naïve Patients with Inactive Chronic Hepatitis B (CHB)
IRAS ID
286901
Contact name
Mark Thursz
Contact email
Sponsor organisation
Altimmune, Inc.
Eudract number
2020-002118-42
Duration of Study in the UK
1 years, 5 months, days
Research summary
This is a Phase 2, randomized, double-blind, placebo-controlled, multicenter clinical trial to evaluate the antiviral effects, immunogenicity, and safety of HepTcell in treatment-naïve patients with inactive CHB and low HBsAg levels (10 to 100 IU/mL).
Chronic hepatitis B (CHB) affects 292 million people worldwide (3.9% of the world’s population), of which 887,000 die annually of complications of the disease. Altimmune, Inc. is developing HepTcell (adjuvanted FP-02.2), an immunotherapeutic vaccine for treatment of CHB, to address the substantial unmet medical need of this patient population. This immunotherapeutic vaccine is specifically designed to enhance T cell immunity in patients with CHB and achieve durable control of the virus. FP-02.2 has been studied in Phase 1 clinical trial conducted in UK and South Korea. Results from phase 1 study established a robust immunogenicity response in patients treated with FP-02.2 in combination with IC31. The magnitude of response increased with each successive dose of FP-02.2 and suggested that additional doses would result in an even more robust immunological response. FP-02.2 was generally safe and well tolerated .
In this Phase 2 clinical trial HepTcell vaccine (FP-02.2) + IC31 will be administered by intramuscular (IM) injection at intervals of 4 weeks for 6 doses to patients. Approximately 80 patients with inactive CHB and low hepatitis B surface antigen (HBsAg) levels (10 to 100 IU/mL) will be randomized in 1:1 to HepTcell or placebo and stratified by study center. Duration for study patient is approximately 76 weeks (a 4-week Screening Period, a 24-week Treatment Period, and a 52-week Follow-Up Period commencing after the last dose of study medication at Week 20)This clinical trial is being sponsored by Altimmune, Inc and will take place at 6 sites in the UK with estimated 15 patients’ enrolment per country.
Lay summary of study results: SYNOPSIS
Name of Sponsor/Company: Altimmune, Inc.
Name of Finished Product: HepTcell Name of Active Ingredient: Adjuvanted FP-02.2
Individual Study Table Referring to Part of the Dossier Volume: Page:Title of Study: Phase 2, Double-blind, Randomized, Placebo-controlled Study of HepTcell (Adjuvanted FP-02.2) as an Immunotherapeutic Vaccine in Treatment-naïve Patients with Inactive Chronic Hepatitis B (CHB)
Investigators and Study Centers: The study was conducted at 43 study centers, including 6 in Germany, 7 in Spain, 4 in Italy, 5 in the UK, 8 in the USA, 6 in Canada, and 7 in Thailand.
Publications (reference): None
Studied period (years):
Date first patient enrolled: 12 August 2021
Date last patient completed: 17 April 2024
Phase of development: 2Objectives:
Primary: • To assess virologic response to HepTcell in treatment-naïve patients with inactive CHB. Secondary: • To assess cellular immune response of HepTcell in treatment-naïve patients with inactive CHB • To assess safety of HepTcell in treatment-naïve patients with inactive CHBMethodology: This was a Phase 2, randomized, double-blind, placebo-controlled, multicenter clinical trial to evaluate the antiviral effects, immunogenicity, and safety of HepTcell in treatment-naïve patients with inactive CHB and low HBsAg levels (10 to 200 IU/mL). After providing written informed consent, patients were to undergo a screening period of up to 35 days. Patients who met eligibility criteria were to be randomized in a 1:1 ratio to receive 6 intramuscular (IM) doses of HepTcell or placebo (normal saline) at study visits 4 weeks apart. Randomization was stratified by study center. Adverse events (AEs) were to be monitored, and blood samples collected for qHBsAg, anti-HBs, HBV DNA, HBV pg-RNA, HBcrAg, and IFN-γ ELISpot assay in PBMCs. Patients were to record any reactogenicity events for 7 days after each administration of study medication in a diary. A visit consisting of a targeted physical examination and safety laboratory tests, including liver panels, was to be conducted 7±2 days after administration of Doses 1 and 2 of study medication. Patients were to be followed for 52 weeks after the last dose of study medication. AEs and concomitant medications were to be recorded from the signing of informed consent to Day 169, and MAEs, NCIs, and IMCs, were to be followed subsequently. Likewise, concomitant medications were to be recorded through Day 169, but only immunosuppressive medications, vaccines, and new HBV treatments or medications associated with MAEs, NCIs, SAEs, hepatitis flares, or hepatic injury were to be recorded beyond that point. A Safety Committee conducted regular blinded reviews of all AEs and reactogenicity events. The safety of study participants was also overseen by an unblinded Data Monitoring Committee (DMC). A sentinel cohort of 12 patients (6 receiving HepTcell and 6 placebo) were to undergo blinded safety review by the Safety Committee 7 to 10 days after all ongoing patients in the sentinel cohort completed the respective dose of study medication to determine whether to continue at that dose to the expanded cohort. If any protocol-defined stopping rules were met in one or more patients and the event(s) deemed possibly or probably related to HepTcell, dosing was to be suspended pending DMC review. If none of the stopping rules were met, randomization and dosing was to continue in the expanded study cohort. Patients were to be unblinded as necessary to assess the relationship between the study medication and events meeting the criteria for Stopping Rules. Investigators were to review the eligibility of all patients prior to dosing to determine if the next treatment was to be administered. Eligibility for the next treatment included: 1) confirmation that patients did not meet a stopping rule; 2) confirmation that the pretreatment liver parameters were within acceptable ranges for treatment; 3) confirmation that patients did not have a new confirmed or suspected immune-mediated medical condition (IMC). If abnormalities of ALT, AST, total bilirubin, direct bilirubin, or international normalized ratio (INR) were reported after dosing was started, protocol-defined management and dosing rules were to be applied.
Number of patients (planned and analyzed): Planned: Approximately 80 patients Enrolled and analyzed (safety population): 84 patients, 41 in the HepTcell group and 43 in the placebo group.
Diagnosis and main criteria for inclusion: • Men and women 18 to 65 years of age, inclusive • Body Mass Index (BMI) 18.0 to 34.9 kg/m2, inclusive • Inactive, treatment-naïve CHB with documented HBsAg positivity for at least 12 months before Day 1. (The history of HBsAg positivity could have been reduced to 6 months provided HBV anti-core IgM antibodies were negative.) • qHBsAg ≥ 10 IU/mL but ≤ 200 IU/mL in the 12 months prior to Screening or from informed consent to randomization. (Patients with more than one qHBsAg value within 12 months prior to randomization were to be deemed eligible if any one measurement was within the eligible range.) • AST, ALT, INR, albumin, total bilirubin and direct bilirubin within normal limits at screening. Note: Patients with Gilbert Syndrome were only eligible for study participation if total bilirubin was ≤ 3.0 mg/dL. ALT and AST elevations up to 1.5 × ULN were allowed if there was evidence of hepatic steatosis, defined as fatty liver on ultrasound or other imaging modality or Fibroscan controlled attenuation parameter (CAP) ≥ 260 dB/m. To qualify under these conditions, HBV DNA was to be < 2000 IU/mL and there was to be no history or signs of liver disease other than fatty liver and HBV.
Test product, dose and mode of administration, batch number: HepTcell (adjuvanted synthetic fluoropeptide hepatitis B immunotherapeutic vaccine) is the final reconstituted product for administration, that consists of a lyophilized mixture of 9 fluoropeptides and mannitol (FP-02.2 drug product), L-histidine buffer, normal saline (to achieve an isotonic, neutral pH), and IC31® (developed by Valneva SE). A dose of 150 μg of each fluoropeptide + IC31 (500/20 nmol KLK/ODN1a) was administered by intramuscular (IM) injection at intervals of 4 weeks for 6 doses. Lot numbers: FP02.02 Lot # P08419; IC31 Lot # P08919; L-Histidine Lot # ALTg100
Duration of treatment: Twenty weeks total: 6 doses at 4-week intervals.Reference therapy, dose and mode of administration: Normal saline placebo for IM injection at intervals of 4 weeks for 6 doses.
Criteria for evaluation (Endpoints):
Efficacy:
Primary • Proportion of patients achieving virologic response, defined as a 1.0-log reduction in quantitative HBsAg (qHBsAg) or serologic clearance of HBsAg, Baseline to Day 169.
Secondary • 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, hepatitis B core-related antigen (HBcrAg) and pre-genomic RNA (pg-RNA) levels, Baseline to Days 85 and 169 • Change in IFN-γ frequency by ELISpot assay in PBMCs, Baseline to Days 85 and 169
Safety: • Incidence and severity of AEs, medically-attended AEs (MAEs), new-onset chronic illnesses (NCIs), and immune-mediated medical conditions (IMCs) • Incidence and severity of local and systemic reactogenicity events • Incidence and duration of hepatitis flares, defined as alanine aminotransferase (ALT) ≥ 3 × upper limit of normal (ULN) and > 100 U/L • Changes in ALT, aspartate aminotransferase (AST), alkaline phosphatase (AP), gamma glutamyl transferase (GGT), bilirubin total and direct, international normalized ratio (INR) and other laboratory parametersSummary – Conclusions
Study Subjects:
A total of 87 patients were randomized and 84 patients were treated in the study. Forty of the 41 patients that received HepTcell and all 43 patients that received placebo completed the study treatment phase. Based on the efficacy and immunogenicity findings from a prespecified interim analysis conducted when all patients were through the treatment phase, the study was terminated and the planned 52-week follow-up period was not completed for patients ongoing at that time.
Efficacy Results: The efficacy and immunogenicity results revealed no meaningful evidence of virologic response in patients treated with HepTcell. A virologic response was observed in only 1 patient in the HepTcell group and there were no significant differences between the HepTcell and placebo groups for changes from baseline in qHBsAg, HBV DNA, HBcrAg, pg-RNA, or IFN-γ levels.
Safety Results: HepTcell was well tolerated with no safety concerns identified. No treatment-emergent SAEs were reported and no patients discontinued study treatment because of TEAEs. The overall incidences of TEAEs, severe TEAEs, and MAEs were numerically lower in the HepTcell group compared with the placebo group. No notable differences were apparent between the HepTcell and placebo groups in the incidence of any individual TEAEs. In both groups, the most commonly reported TEAE was COVID-19. Except for a severe event of blood creatine phosphokinase increased unrelated to study drug in 1 patient in the HepTcell group, all TEAEs in this group were mild or moderate in severity. The only IMC reported was vitiligo in 1 patient in the HepTcell group. The majority of reactogenicity events were mild in severity and no severe reactogenicity events were reported in the HepTcell group. The most commonly reported reactogenicity events after each dose in the HepTcell group were pain and tenderness at the injection sit, with a lower incidence of these events after the sixth dose compared with the first. No hepatitis flares were reported in the HepTcell group. Laboratory values and vital signs measurements were comparable in the HepTcell and placebo groups. No clinically significant ECG or physical exam findings were reported in the HepTcell group at Day 169.Conclusions: HepTcell was well tolerated with no safety concerns identified. The efficacy and immunogenicity results revealed no meaningful evidence of virologic response. Thus, the decision was made do terminate the clinical study and discontinue further development of HepTcell.
Date of the Report: 09 July 2024
Has the registry been updated to include summary results?: Yes
If yes - please enter the URL to summary results: Study data is shared in the following: 1) Spain: Reec - Spanish portal for Clinical Trials: https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Fclick.pstmrk.it%2F3ts%2Freec.aemps.es%252Freec%252Fpublic%252Fdetail.html%2FNBTI%2Ft563AQ%2FAQ%2F4c089ce0-091b-472e-87d2-ee4393d8d3f9%2F1%2FF3R_rdFvEC&data=05%7C02%7Csurreyborders.rec%40hra.nhs.uk%7C6d949d83cf6d47d8e95908dcc6a29aeb%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638603648883889754%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C0%7C%7C%7C&sdata=lKVtalz8gbiPkarhgk007zg8wuxTAnGpEO6d%2BgQbMCM%3D&reserved=0 2) ClinicalTrials.gov: https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Fclick.pstmrk.it%2F3ts%2Fclinicaltrials.gov%252Fsearch%253Fterm%253DALT-301-202%2FNBTI%2Ft563AQ%2FAQ%2F4c089ce0-091b-472e-87d2-ee4393d8d3f9%2F2%2FXUrrUIe7_X&data=05%7C02%7Csurreyborders.rec%40hra.nhs.uk%7C6d949d83cf6d47d8e95908dcc6a29aeb%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638603648883900589%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C0%7C%7C%7C&sdata=b0Uab8kGDpAuoOHGbcYcVEbZ1wrddw9LZmqk94i5S78%3D&reserved=0 – study results pending
If no – why not?:
Did you follow your dissemination plan submitted in the IRAS application form (Q A51)?: Pending
If yes, describe or provide URLs to disseminated materials:
If pending, date when dissemination is expected: 26/03/2025
If no, explain why you didn't follow it:
Have participants been informed of the results of the study?: No
If yes, describe and/or provide URLs to materials shared and how they were shared:
If pending, date when feedback is expected:
If no, explain why they haven't: A dissemination plan to inform the participants of the ALT-301-202 study results was not developed as this was not the aim of the Sponsor. Principal Investigators have been adequately informed regarding results for ALT-301-202 study. Participants who wishes to know more about the results can ask their corresponding principal investigator.
Have you enabled sharing of study data with others?: Yes
If yes, describe or provide URLs to how it has been shared: Study data is shared in the following: 1) Spain: Reec - Spanish portal for Clinical Trials: https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Fclick.pstmrk.it%2F3ts%2Freec.aemps.es%252Freec%252Fpublic%252Fdetail.html%2FNBTI%2Ft563AQ%2FAQ%2F4c089ce0-091b-472e-87d2-ee4393d8d3f9%2F1%2FF3R_rdFvEC&data=05%7C02%7Csurreyborders.rec%40hra.nhs.uk%7C6d949d83cf6d47d8e95908dcc6a29aeb%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638603648883908363%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C0%7C%7C%7C&sdata=S0WcNAm634Z%2FYIoEVheyfxacL52LtguzTR9wJPfqw8g%3D&reserved=0 2) ClinicalTrials.gov: https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Fclick.pstmrk.it%2F3ts%2Fclinicaltrials.gov%252Fsearch%253Fterm%253DALT-301-202%2FNBTI%2Ft563AQ%2FAQ%2F4c089ce0-091b-472e-87d2-ee4393d8d3f9%2F2%2FXUrrUIe7_X&data=05%7C02%7Csurreyborders.rec%40hra.nhs.uk%7C6d949d83cf6d47d8e95908dcc6a29aeb%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638603648883913663%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C0%7C%7C%7C&sdata=ehFCnLuzt7OEKSEw%2B1Ecd6TT2LeLsogKlTNUoBWo8QM%3D&reserved=0 – Pending, to be completed by 26Mar2025
If no, explain why sharing hasn't been enabled:
Have you enabled sharing of tissue samples and associated data with others?: No
If yes, describe or provide a URL:
If no, explain why: There are no plans of sharing tissue samples and associated data for the ALT-301-202 study with others
Submitted on: 27/08/2024REC name
London - Surrey Borders Research Ethics Committee
REC reference
20/LO/1115
Date of REC Opinion
9 Dec 2020
REC opinion
Further Information Favourable Opinion