ANRS HB07 IP-Cure-B Proof of Concept (PoC) Clinical Trial. Educating the Liver Immune Environment Through TLR8 Stimulation Followed by NUC Discontinuation

NCT05045261 | Unknown Phase 2 DMC FDA Drug

• 2 other identifiers: ANRS HB07 IP CURE B2020-004376-18
• Study Type: interventional
• Target: 100
• Locations: 4 countries
• Sites: 8

Brief Summary

The ANRS HB07 IP-cure-B study is a proof of concept Phase II clinical trial in HBeAg negative virally suppressed non-cirrhotic CHB patients. It will explore whether stopping NUC or stopping NUC after SLGN administration can increase the rate of HBsAg decline compared to standard of care CHB treatment.

Conditions

Hepatitis B, Chronic

Outcome Measures

Primary Outcomes (1)

• Efficacy : Percentage of subjects with ≥ 1.0 log10 IU/mL decline of HBsAg at week 76

  percentage of subjects with ≥ 1.0 log10 IU/mL decline of HBsAg at week 76 compared to baseline

  Week 76

Secondary Outcomes (13)

• Efficacy : Percentage of subjects with HBsAg ≥ 0.3 log10 IU/mL decline

  Weeks 12, 24, 28, 36, 48, 76

• Efficacy : Percentage of subjects with HBsAg ≥ 0.5 log10 IU/mL decline

  Weeks 12, 24, 28, 36, 48, 76

• Efficacy : Percentage of subjects with HBsAg ≥ 1.0 log10 IU/mL decline

  Weeks 12, 24, 28, 36, 48, 76

• Efficacy : Percentage of subjects with HBsAg < 100 IU/mL

  Weeks 12, 24, 28, 36, 48, 76

• Efficacy : Percentage of subjects with HBsAg < 10 IU/mL

  Weeks 12, 24, 28, 36, 48, 76

Study Arms (3)

A - Standard of care NUC

NO INTERVENTION

Patients will continue their standard of care NUC treatment

B - NUC discontinuation

EXPERIMENTAL

Patients will stop their NUC treatment 28 weeks after enrolment

Drug: Discontinuation of NUC treatment in arms B and C

C - NUC discontinuation after SLGN treatment

EXPERIMENTAL

Patients will take from enrolment * their standard of care NUC treatment for 28 weeks then stop * 3mg SLGN weekly for 24 weeks then stop

Drug: administration of SLGN in arm C; Drug: Discontinuation of NUC treatment in arms B and C

Interventions

administration of SLGN in arm C DRUG

administration of 3mg SLGN weekly for 24 weeks in arm C

C - NUC discontinuation after SLGN treatment

Discontinuation of NUC treatment in arms B and C DRUG

NUC treatment will be stopped after 28 weeks in arms B and C

B - NUC discontinuation; C - NUC discontinuation after SLGN treatment

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with HBeAg negative CHB on documented NUC for ≥ 3 years with HBV DNA LLOQ by local assay by polymerase chain reaction (PCR) documented at least annually over the last 3 years. NUC can include only tenofovir disoproxil fumarate (TDF), tenofovir alafemanide fumarate (TAF) or entecavir,
• HBsAg ≥ 100 IU/mL but \< or = 3,000 IU/mL at screening,
• Male and female subjects aged 18 to 70 years (inclusive) at the day of screening,
• Ultrasound, computed tomography (CT) scan, or magnetic resonance imaging (MRI) within 6 months of screening date with no evidence of hepatocellular carcinoma (HCC),
• No evidence of advanced fibrosis or cirrhosis at screening: elastography (Fibroscan) value ≤ 9 kPa and ultrasonography without any sign of cirrhosis and platelets ≥ 150x109/L,
• No evidence of advanced fibrosis or cirrhosis before the onset of NUC therapy,
• HBV DNA \< 20 IU/mL at screening,
• ALT levels within the normal range of the local lab (\< ULN) at screening,
• Negative urine or serum pregnancy test (for women of childbearing potential) documented within the 24-hour period prior to the first dose of IMP. If the urine pregnancy test is positive, a follow-up serum test is required for confirmation,
• Women of childbearing potential must agree to use a highly effective method of contraception from screening throughout the study period and for 7 days after the last dose of study drug. Men with female partners who are of childbearing potential must agree that they or their partners will use a highly effective method of contraception from screening throughout the study period and for 7 days after the last dose of study drug.
• Women of childbearing potential are sexually mature women who have not undergone bilateral oophorectomy or hysterectomy; or who have not been postmenopausal (ie, who have not menstruated at all) for at least 1 year.
• Highly effective methods of contraception not using hormonal contraceptives will be intrauterine device, tubal sterilization, Essure microinsert system; male partner sterilization; or total abstinence from heterosexual intercourse, when this is the preferred and usual lifestyle of the subject. Note: The double-barrier method (eg, synthetic condoms, diaphragm, or cervical cap with spermicidal foam, cream, or gel), periodic abstinence (such as calendar, symptothermal, post-ovulation), withdrawal (coitus interruptus), lactational amenorrhea method, and spermicide only are not acceptable as highly effective methods of contraception.
• Screening Electrocardiogram (ECG) without clinically significant abnormalities and with QTcF interval (QT corrected using Fridericia's formula) ≤ 450 msec for males and ≤ 470 msec for females,
• Must be willing and able to comply with all study requirements,
• Must have the ability to understand and sign a written informed consent form (ICF),

You may not qualify if:

• Any history of decompensation of liver disease including history of ascites, encephalopathy and gastrointestinal bleeding,
• Any sign of oesophageal and/or gastric varices,
• Laboratory parameters not within defined thresholds:
• White blood cells \< 4,000 cells/μL (\< 4.0×109/L);
• Hemoglobin \< 11 g/dL (\< 110 g/L) for females, \< 13 g/dL (\< 130 g/L) for males;
• Platelets \< 130,000 per μL (\< 130×109/L);
• Albumin \< 3.5 g/dL (\< 35 g/L);
• International normalized ratio (INR) \> 1.5;
• Total bilirubin \> 1.2 mg/dL (\> 20.52 μmol/L). Note: subjects with an elevated indirect bilirubin and known Gilbert's disease can be included if direct bilirubin is within normal limits.
• Alpha-fetoprotein (AFP) \> 20 ng/mL;
• Creatinine clearance (using the Cockcroft-Gault method) \< 60 mL/min;
• Co-infection with hepatitis C virus (HCV) (antibodies anti-HCV positive), human immunodeficiency virus type 1 (HIV-1) (antibodies anti-HIV positive) or hepatitis D virus (HDV) (antibodies anti-HDV positive),
• Evidence or history or suspicion 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). Note: subjects under evaluation for possible malignancy are not eligible.
• Significant cardiovascular, pulmonary, or neurological disease,

Sponsors & Collaborators

• ANRS, Emerging Infectious Diseases: lead
• EUCLID Clinical Trial Platform: collaborator

Study Sites (8)

Hepatology Department, Hospices Civils de Lyon

Lyon, 69004, France

RECRUITING

Hepato-gastroenterology department, Hôpital Saint-Joseph

Marseille, 13008, France

RECRUITING

Service d'Hépato-gastroentérologie, Hôpital de Brabois

Nancy, 54500, France

RECRUITING

Service d'Hépato-gastroentérologie Hôpital Pitié Salpêtrière

Paris, 75013, France

RECRUITING

Department of Internal Medicine Clinic for Internal Medicine II - Gastroenterology, Hepatology, Endocrinology and Infectiology, Universitat Klinikum in Freiburg

Freiburg im Breisgau, 79106, Germany

NOT YET RECRUITING

Gastroenterology and Hepatology Division, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Milan, 20122, Italy

NOT YET RECRUITING

Department of General and Specialized Medical AreaAzienda Ospedaliera, University Hospital of Parma

Parma, 43126, Italy

NOT YET RECRUITING

Internal Medicine and Hepatology, Vall d'Hebron University Hospital

Barcelona, 08035, Spain

NOT YET RECRUITING

MeSH Terms

Conditions

Hepatitis B, Chronic

Condition Hierarchy (Ancestors)

Hepatitis B; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Fabien ZOULIM, MD

  Hepatology Department, Hospices Civils de Lyon

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Carole CAGNOT, PhD

CONTACT

+33 1 53 94 80 60; carole.cagnot@anrs.fr

Laetitia MOINOT, PharmD

CONTACT

+33 5 57 57 92 85; laetitia.moinot@u-bordeaux.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 4, 2021
• First Posted: September 16, 2021
• Study Start: February 1, 2022
• Primary Completion: June 30, 2024
• Study Completion: June 30, 2024
• Last Updated: March 14, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will share

Locations

IT (2); ES (1); DE (1); FR (4)