SELGANTOLIMOD for Chronic hepatitis B

Inclusion criteria

• {"criterion_text":"- Patients with HBeAg negative CHB on documented NUC for ≥ 3 years with HBV DNA < 20 IU/mL by local assay by polymerase chain reaction (PCR) documented at least 3 times over the last 1.5 year. NUC can include only tenofovir/TDF, tenofovir/TAF or entecavir,\n- 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. a) 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. b) 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.\n- 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,\n- Must be willing and able to comply with all study requirements,\n- Must have the ability to understand and sign a written informed consent form (ICF),\n- Participant covered by Health Insurance (when requested by local regulations)\n- HBsAg ≥ 100 IU/mL but ≤6,000 IU/mL at screening,\n- Male and female subjects aged 18 to 70 years (inclusive) at the day of screening,\n- Ultrasound, computed tomography (CT) scan, or magnetic resonance imaging (MRI) within 6 months of screening date with no evidence of hepatocellular carcinoma (HCC),\n- 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, Note: if the abdominal ultrasound was done as part of the routine care within 6 months prior to the screening date, the result may be used for the validation of the participant's eligibility, without being done again at screening\n- No evidence of cirrhosis before the onset of NUC therapy,\n- HBV DNA < 20 IU/mL at screening,\n- ALT levels ≤ 1.5 ULN at screening,\n- 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,"}

Exclusion criteria

• {"criterion_text":"- Any history of decompensation of liver disease including history of ascites, encephalopathy and gastrointestinal bleeding,\n- 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,\n- Concomitant treatment with the following medications (if taken within 21 days prior the baseline visit through the end of treatment plus 7 days)/diet: a)\tHematologic stimulating agents (eg, erythropoiesis-stimulating agents; granulocyte colony stimulating factor [GCSF]; and thrombopoietin [TPO] mimetics), b)\tPotent CYP3A4 inhibitors or inducers, including but not limited to antifungals (fluconazole, ketoconazole…), antibiotics (telithromycin, rifabutin, rifampicin…), St. John's Wort, grapefruit juice, anticonvulsants (carbamazepine, phenobarbital, phenytoin…) etc, c)\tImmunosuppressant (except short term use of prednisone as a steroid burst [≤ 1 week of use]) and cytotoxic medications,\n- Known hypersensitivity or resistance to study drugs or formulation excipients,\n- Diagnosis of autoimmune disease (e.g., systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, autoimmune hepatitis, sarcoidosis, psoriasis of greater than mild severity, autoimmune uveitis), poorly controlled diabetes mellitus, significant psychiatric illness, severe chronic obstructive pulmonary disease, hemoglobinopathy, retinal disease, or immunosuppressed patients,\n- Use of another investigational agent within 6 months of screening and during the whole \tduration of the trial,\n- Current alcohol or substance abuse judged by the Investigator to potentially interfere with compliance,\n- Females who are breastfeeding, pregnant or may wish to become pregnant during the study,\n- Female subjects unwilling to refrain from egg donation and in vitro fertilization during and until at least 7 days after the last study drug dose. Male subjects unwilling to refrain from sperm donation during and until at least 7 days after the last study drug,\n- Any medical condition that, in the opinion of the investigator, could interfere with evaluation of the study objectives or safety of the subjects.\n- Any sign of oesophageal and/or gastric varices,\n- Laboratory parameters not within defined thresholds: White blood cells count < 2,500 cells/μL (< 2.5 ×109/L) and neutrophil count < 1,500 cells/μL (or < 1,000 cells/μL if considered a physiological variant in subjects of African descent); Note: in order to verify this criterion, the ethnicity of the participants will be collected in the eCRF. b) Hemoglobin < 11 g/dL (< 110 g/L) for females, < 13 g/dL (< 130 g/L) for males; c) Platelets < 130,000 per μL (< 130×109/L); d) Albumin < 3.5 g/dL (< 35 g/L); e) International normalized ratio (INR) > 1.5; f) 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. g)\tAlpha-fetoprotein (AFP) > 20 ng/mL; h)\tCreatinine clearance (using the Cockcroft-Gault method) < 60 mL/min; NB: Biological parameters outside of these values should be reviewed by the coordinating investigators who should specify the clinically significance. Results considered non-clinically significant by the coordinating investigators are accepted.\n- Co-infection with hepatitis C virus (HCV) (HCV RNA positive and patients cured for less than one year prior to the screening date)*, co-infection with human immunodeficiency virus type 1 (HIV-1) (antibodies anti-HIV positive) or hepatitis D virus (HDV) (antibodies anti-HDV positive), *Note: co-infection HCV The following patients are eligible: . Patients treated → HCV PCR negative one year after treatement discontinuation . Non-treated patients: anti HCV positive, HCV PCR negative, profile known and confirmed for at least 1 year\n- Evidence or history or suspicion of hepatocellular carcinoma,\n- 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.\n- Significant cardiovascular, pulmonary, or neurological disease,\n- Received solid organ or bone marrow transplant,\n- Received within 3 months of screening or expected to receive prolonged therapy with immunomodulators (eg, corticosteroids, anti-TNF) or biologics (eg, monoclonal antibody, IFN),"}

Primary endpoints

• {"endpoint_text":"- The primary endpoint for efficacy is the percentage of subjects with ≥ 1.0 log10 IU/mL decline of HBsAg at week 76 compared to baseline.","definition_or_measurement_approach":"Percentage of subjects achieving a ≥ 1.0 log10 IU/mL decline in HBsAg at week 76 versus baseline (measurement by HBsAg quantitative assay at baseline and week 76)."}

Secondary endpoints

• {"endpoint_text":"- Percentage of subjects with HBsAg ≥ 0.3 log10 IU/mL decline at weeks 12, 24, 28, 36, 48, 76 compared to baseline","definition_or_measurement_approach":"Proportion of subjects with ≥0.3 log10 IU/mL HBsAg decline at specified weeks versus baseline (measured at weeks 12,24,28,36,48,76)."}
• {"endpoint_text":"- Percentage of subjects with HBsAg ≥ 0.5 log10 IU/mL decline at weeks 12, 24, 28, 36, 48, 76 compared to baseline","definition_or_measurement_approach":"Proportion of subjects with ≥0.5 log10 IU/mL HBsAg decline at specified weeks versus baseline (measured at weeks 12,24,28,36,48,76)."}
• {"endpoint_text":"- Percentage of subjects with HBsAg ≥ 1.0 log10 IU/mL decline at weeks 12, 24, 28, 36, 48 compared to baseline","definition_or_measurement_approach":"Proportion of subjects with ≥1.0 log10 IU/mL HBsAg decline at specified earlier timepoints versus baseline (measured at weeks 12,24,28,36,48)."}
• {"endpoint_text":"- Percentage of subjects with HBsAg < 100 IU/mL at weeks 12, 24, 28, 36, 48, 76","definition_or_measurement_approach":"Proportion of subjects with HBsAg level <100 IU/mL at each specified visit."}
• {"endpoint_text":"- Percentage of subjects with HBsAg < 10 IU/mL at weeks 12, 24, 28, 36, 48, 76","definition_or_measurement_approach":"Proportion of subjects with HBsAg level <10 IU/mL at each specified visit."}
• {"endpoint_text":"- Percentage of subjects with HBsAg loss at weeks 12, 24, 28, 36, 48, 76 and time to HBsAg loss since baseline","definition_or_measurement_approach":"Proportion of subjects with HBsAg loss at listed visits and time-to-event analysis for time from baseline to HBsAg loss."}
• {"endpoint_text":"- Percentage of subjects with HBsAb seroconversion at weeks 12, 24, 28, 36, 48, 76 and time to HBsAb seroconversion","definition_or_measurement_approach":"Proportion with HBsAb seroconversion at listed visits and time-to-event for seroconversion."}
• {"endpoint_text":"- Changes in serum HBsAg, HBcrAg, HBV RNA and HBV DNA levels in log10 IU/mL from baseline to each timepoint available from study schedule. 48, 76.","definition_or_measurement_approach":"Change from baseline in log10 IU/mL for HBsAg, HBcrAg, HBV RNA and HBV DNA at each scheduled visit (including weeks 48 and 76)."}
• {"endpoint_text":"- Percentage of subjects reporting a grade 3 or 4 AE","definition_or_measurement_approach":"Proportion of subjects with at least one adverse event of grade 3 or 4 (safety assessed throughout study)."}
• {"endpoint_text":"- Percentage of subjects with at least one AE","definition_or_measurement_approach":"Proportion of subjects reporting any adverse event during study period."}
• {"endpoint_text":"- Percentage of subjects with ALT flares at each time point (ALT flares defined as ≥ 10 x ULN)","definition_or_measurement_approach":"Proportion of subjects with ALT elevations meeting the definition ≥10×ULN at each visit."}
• {"endpoint_text":"- Percentage of subjects in whom NUC treatment has been re-initiated","definition_or_measurement_approach":"Proportion of subjects who had NUC therapy re-started during study follow-up."}
• {"endpoint_text":"- To assess and compare health-related quality of life, measured using EQ-5D-5L utility score (collected with a self-completed questionnaire, see appendix 1) at baseline, weeks 28 and 76 (WP7, see appendix 2).","definition_or_measurement_approach":"EQ-5D-5L utility scores collected by self-completed questionnaire at baseline, week 28 and week 76; comparison of scores across arms and timepoints."}

France

Earliest CTIS Part Ii Submission Date

27-08-2024

Latest Decision Or Authorization Date

10-10-2024

Processing Time Days

44

Number Of Sites

5

Number Of Participants

24

Italy

Earliest CTIS Part Ii Submission Date

27-08-2024

Latest Decision Or Authorization Date

24-09-2024

Processing Time Days

28

Number Of Sites

2

Number Of Participants

15

Spain

Earliest CTIS Part Ii Submission Date

27-08-2024

Latest Decision Or Authorization Date

03-09-2024

Processing Time Days

7

Number Of Sites

1

Number Of Participants

9

Germany

Earliest CTIS Part Ii Submission Date

27-08-2024

Latest Decision Or Authorization Date

05-12-2024

Processing Time Days

100

Number Of Sites

1

Number Of Participants

3

Primary sponsor

Full Name

ANRS Maladies Infectieuses Emergentes

Organisation Type

Laboratory/Research/Testing facility

Country Of Registered Address

France