Pomalidomide in people with chronic hepatitis B virus (HBV) infection: Safety and immune-enhancing effects (The PIPPI Study)

Prior treatment

• Currently receiving other systemic immune-enhancing or immunosuppressive therapy (immunisation and locally applied agents are allowed) or having received any of those within 28 days prior to study entry
• Current (within the previous two weeks) use of strong CYP1A2 inhibitors (including abametapir, ciprofloxacin, enoxacin, fluvoxamine and pixantrone) at enrolment.
• Received peg- IFNα treatment within 12 months
• Co-infection with HIV, hepatitis C or D (Individuals with prior hepatitis C infection that is now cleared are eligible for enrolment)
• Current or recent gastrointestinal disease or gastrointestinal surgery that may impact the absorption of the investigational drug
• Prior or current lenalidomide, thalidomide or pomalidomide treatment or any condition where those treatments are indicated.
• Active alcohol or substance use that, in the Investigator's opinion, will prevent adequate compliance with study therapy or procedures
• Currently receiving anticoagulant therapy

Other illness

• History of malignancy or transplantation, excluding adequately treated basal cell carcinoma
• Significant cardiac dysfunction
• Known allergy or hypersensitivity to pomalidomide
• History of procoagulant disorders or venous/arterial thromboembolism

Lab values

• Impaired renal function with estimated creatinine clearance (eGFR) <50 mL/min
• The following laboratory values at screening (lab tests may be repeated, as clinically indicated, to obtain acceptable values before failure at screening is concluded but supportive therapies are not to be administered within the week prior to screening tests): Hepatic transaminases (AST or ALT) ≥2 x upper limit of normal (ULN), eGFR <50 mL/min, Platelet count ≤100 x109/L, Absolute neutrophil count ≤1.5x109/L, Haemoglobin <10,0 g/dL, Total lymphocyte count <800 cells/mL
• Hepatic impairment defined as ALT >2 x upper limit of normal

Other

• Participation in other clinical trials within the last 6 months
• Regular NSAID usage (>7 days continuous use in the last month) and/or unable to avoid regular NSAID use on the trial.
• Women who are pregnant or breastfeeding or Women of Child Bearing Potential (WOCBP) who are unwilling or unable to use an acceptable method of contraception to avoid pregnancy as specified in the inclusion criteria
• Unable or unwilling to adhere to protocol procedures
• Liver fibrosis or cirrhosis as determined by histological examination of a liver biopsy specimen (Metavir = or >3 or Ishak fibrosis score = or >3) or, in the absence of an appropriate liver biopsy, defined clinically with a FibroScan result >9 kPa within 6 months of screening

• Evidence of chronic HBV infection defined as positive for HBsAg for >6 months
• Age 18-70 years
• HBeAg positive or negative at screening
• Not on nucleoside analogue treatment
• Ability and willingness to provide informed consent
• A female, may be eligible to enter and participate in the study if she: o Is of non-child-bearing potential defined as either post-menopausal (12 months of spontaneous amenorrhea and ≥ 45 years of age) or physically incapable of becoming pregnant with documented tubal ligation, hysterectomy, or bilateral oophorectomy or, o Is of child-bearing potential with a negative pregnancy test at both screening and day 0 and agrees to use one of the following methods of contraception to avoid pregnancy: - Complete abstinence from penile-vaginal intercourse from 2 weeks prior to administration of IP, throughout the study, and for at least 2 weeks after discontinuation of all study medications - Any intrauterine device (IUD) with published data showing that the expected failure rate is <1% per year  Male partner sterilization confirmed prior to the female subject’s entry into the study, and this male is the sole partner for that subject - Approved hormonal contraception - Any other method with published data showing that the expected failure rate is <1% per year - Any contraception method must be used consistently, in accordance with the approved product label and for at least 2 weeks after discontinuation of study therapy.
• All participants must agree not to participate in a conception process (e.g. active attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization, egg donation) during the study
• Heterosexually active male if they are: willing to use an effective method of contraception (anatomical sterility in self that is confirmed prior to study entry) or agree on the use of an effective method of contraception with an effective failure rate of < 1% by his partner (hormonal contraception, intra-uterine device (IUD), or anatomical sterility) from the day prior to the first dose and for at least 4 weeks after discontinuation of study drug.