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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Region Midtjylland

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02]

Trial duration

19 Aug 2025 → ongoing

Decision date (initial)

2025-05-21

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To determine the safety of pomalidomide in people with chronic hepatitis B

Secondary objectives 2

1. To determine the impact of pomalidomide on NK cell cytotoxicity in people living with CHB
2. To determine impact of pomalidomide on HBV-specific CD8+ T cell function and its effect on liver function, frequency of HBsAg loss and biomarkers of HBV persistence

Conditions and MedDRA coding

Hepatitis B virus infection

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Evidence of chronic HBV infection defined as positive for HBsAg for >6 months
2. Age 18-70 years
3. HBeAg positive or negative at screening
4. Not on nucleoside analogue treatment
5. Ability and willingness to provide informed consent
6. 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.
7. 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
8. 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.

Exclusion criteria 20

1. Participation in other clinical trials within the last 6 months
2. Known allergy or hypersensitivity to pomalidomide
3. Prior or current lenalidomide, thalidomide or pomalidomide treatment or any condition where those treatments are indicated.
4. Unable or unwilling to adhere to protocol procedures
5. Active alcohol or substance use that, in the Investigator's opinion, will prevent adequate compliance with study therapy or procedures
6. 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
7. Hepatic impairment defined as ALT >2 x upper limit of normal
8. History of procoagulant disorders or venous/arterial thromboembolism
9. Currently receiving anticoagulant therapy
10. Regular NSAID usage (>7 days continuous use in the last month) and/or unable to avoid regular NSAID use on the trial.
11. 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
12. Current (within the previous two weeks) use of strong CYP1A2 inhibitors (including abametapir, ciprofloxacin, enoxacin, fluvoxamine and pixantrone) at enrolment.
13. Received peg- IFNα treatment within 12 months
14. History of malignancy or transplantation, excluding adequately treated basal cell carcinoma
15. Co-infection with HIV, hepatitis C or D (Individuals with prior hepatitis C infection that is now cleared are eligible for enrolment)
16. Impaired renal function with estimated creatinine clearance (eGFR) <50 mL/min
17. Significant cardiac dysfunction
18. Current or recent gastrointestinal disease or gastrointestinal surgery that may impact the absorption of the investigational drug
19. 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
20. 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Safety defined as treatment-emerging adverse events (AEs) = or > grade 3 probably or definitely related to pomalidomide.
2. Safety defined as all other treatment-emerging AEs, graded according to severity and assessed as either not related or possibly, probably or definitely related to pomalidomide

Secondary endpoints 6

1. Quantitative plasma levels of HBV DNA
2. Quantitative plasma levels of HBsAg
3. Serum titres of anti-HBs and anti-HBe
4. Levels of the liver function tests (LFTs) including ALT, bilirubin and PP
5. Numbers, proportions and subset distribution of NK cells including changes in the proportion of cytotoxic and dysfunctional NK cells as determined by expression of CD56, CD16, activating and inhibitory markers using flow cytometry
6. The frequency of CD4 and/or CD8 T-cell responses to HBV peptides measured either by intracellular cytokine staining (ICS), activation induced marker (AIM) assay or by ELISPOT and the proportion of polyfunctional CD8+ T cells

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Region Midtjylland

Sponsor organisation

Region Midtjylland

Address

Palle Juul-Jensens Boulevard 99

City

Aarhus N

Postcode

8200

Country

Denmark

Scientific contact point

Organisation

Region Midtjylland

Contact name

Infectious Diseases, Aarhus University Hospital

Public contact point

Organisation

Region Midtjylland

Contact name

Infectious Diseases, Aarhus University Hospital

Third parties 2

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 16 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications