Safety and Immunotherapeutic Activity of Cemiplimab in Participants With HBV on Suppressive Antiviral Therapy

  • End date
    Jun 27, 2023
  • participants needed
  • sponsor
    National Institute of Allergy and Infectious Diseases (NIAID)
Updated on 25 February 2022


The purpose of this study is to evaluate the safety and immunotherapeutic activity of cemiplimab in participants with hepatitis B virus (HBV) on suppressive antiviral therapy.


The study consists of up to three cemiplimab dose cohorts (n=10 participants each). The cohorts will open sequentially, based on the safety of the previous cohort. Cohort 1 will open first to examine the lowest dose. When Cohort 1 participants have completed study week 18 visit and there are no safety concerns, Cohort 2 will open for enrollment. A similar assessment will be conducted with Cohort 2 to make a decision on opening Cohort 3. In each cohort, participants enter the study 6 weeks prior to initiation of treatment. The 6-week lead-in period is followed by a 6-week treatment period where two infusions of cemiplimab are administered 6 weeks apart, at study weeks 6 and 12.

The total study duration per participant is 90 weeks, including 78 weeks of follow-up after the treatment period. Study visit schedule includes visits at entry, and weeks 6, 7, 8, 10, 12, 13, 14, 16, 17, 18, 22, 24, 30, 36, 54, 72 and 90. Evaluations include: a medical and medication history; assessment of HBV antiviral therapy adherence; physical exam; blood, urine, and fecal collection; rectal swab; liver biopsy and fine needle aspiration; and optional leukapheresis.

Condition Hepatitis B Virus
Treatment Cemiplimab
Clinical Study IdentifierNCT04046107
SponsorNational Institute of Allergy and Infectious Diseases (NIAID)
Last Modified on25 February 2022


Yes No Not Sure

Inclusion Criteria

Chronic HBV infection (defined as hepatitis B surface antigen [HBsAg] positive)
Receiving treatment at the time of study entry and for 12 months prior to study entry with HBV-active nucleos(t)ides, with tenofovir- or entecavir-containing therapy: tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF), TDF/emtricitabine (FTC), TAF/FTC, or entecavir
Ability and willingness of participant to provide informed consent
Ability and willingness of participant to continue HBV antiviral therapy throughout the study
Weight 40 kg and <200 kg
Evidence of limited or no evidence of fibrosis (F0-F2) by liver biopsy or non-invasive alternative, as defined in the study protocol
The following laboratory values obtained within 42 days prior to study entry
HBV DNA level <20 IU/mL with prior documented pre-treatment elevation of HBV DNA, with or without a liver biopsy confirming chronic active hepatitis B
Documentation of hepatitis B e antigen (HBeAg) status (positive or negative)
Hemoglobin 14.0 g/dL for male, 12.0 g/dL for female participants
Platelets 150,000/mm^3
Absolute neutrophil count (ANC) >1500/mm^3
International normalized ratio (INR) 1.1
Albumin 3.5 g/dL
Creatinine Cl 60 mL/min, as calculated by the Cockcroft-Gault equation
NOTE: A calculator for the Cockcroft-Gault equation is available on the DMC website at [](
Aspartate aminotransferase (AST) serum glutamic:oxaloacetic transaminase (SGOT) <1.25 x ULN
ALT serum glutamic:pyruvic transaminase (SGPT) <1.25 x ULN
Direct bilirubin 1.0 x ULN
AM cortisol >10 mcg/dL and <ULN
NOTE A: Female participants on estrogen-containing oral contraception or other exogenous estrogen treatment may repeat the AM cortisol as part of screening to determine eligibility. AM cortisol should be drawn prior to 12 noon or per local lab requirements
NOTE B: Participants with a low cortisol level that was drawn after 10:00 AM may repeat the AM cortisol as part of screening to determine eligibility
Normal creatinine phosphokinase (CPK) level
Thyroid stimulating hormone (TSH) and free thyroxine (T4) level within normal limits
Fasting blood glucose <126 mg/dL
Interferon-gamma release assay (IGRA) for tuberculosis (TB) with negative results within 90 days prior to study entry, OR prior positive TB IGRA or positive purified protein derivative (PPD) skin test with documented evidence of completed prophylaxis treatment
HCV antibody negative result within one year prior to study entry; or if the participant is HCV antibody positive, an unquantifiable HCV RNA result (< lower limit of quantification [LLOQ], either target detected, or target not detected) within 42 days prior to study entry
Karnofsky performance score 90 within 42 days prior to entry
For female participants of reproductive potential, a negative urine or serum pregnancy test at screening, and again within 48 hours prior to study entry
All participants must agree not to participate in a conception process (e.g., active attempt to become pregnant or to impregnate, sperm donation, oocyte donation, in vitro fertilization)
When participating in sexual activity that could lead to pregnancy, participants must agree to use at least two reliable forms of contraceptive simultaneously, over the time period of 36 weeks following study entry (to include time period up to 6 months after last infusion). Such methods include
Condoms (male or female) with or without a spermicidal agent
Diaphragm or cervical cap with spermicide
Intrauterine device (IUD)
Tubal ligation
Hormone-based contraceptive
NOTE: Providers and participants should be advised that not all contraceptive choices listed above can prevent HBV transmission. Study participants who are sexually active with HBV negative or unknown HBV serostatus partners should be advised that they need to consider effective strategies to reduce the risk of HBV transmission and meet the requirement for effective contraception during their participation in the study. Study participants should discuss contraceptive choices and HBV risk-reduction methods with their health care provider
Participants who are not of reproductive potential (women who have been post-menopausal for at least 24 consecutive months or have undergone hysterectomy and/or bilateral oophorectomy or salpingectomy or men who have documented azoospermia) are eligible without requiring the use of contraceptives. Acceptable documentation of menopause or sterilization is specified below
Written or oral documentation communicated by clinician or clinician's staff of one of the following
Physician report/letter
Operative report or other source documentation in the patient record (a laboratory report of azoospermia is required to document successful vasectomy)
Discharge summary
Follicle stimulating hormone-release factor (FSH) measurement elevated into the menopausal range as established by the reporting laboratory
Intention to comply with the dosing instructions for study drug administration and ability to complete the study schedule of assessments

Exclusion Criteria

Any malignancy within the 5 years prior to study entry or current malignancy requiring cytotoxic therapy
NOTE: A history of non-melanoma skin cancer (e.g., basal cell carcinoma or squamous cell skin cancer) at any time is not exclusionary
Current chronic, acute, or recurrent bacterial, fungal, or viral (other than HBV) infections that are serious, in the opinion of the site investigator, and that required systemic therapy within 30 days prior to study entry
Prior history of or active autoimmune disorders including but not limited to inflammatory bowel diseases, scleroderma, severe psoriasis, myocarditis, uveitis, pneumonitis, systemic lupus erythematosus, rheumatoid arthritis, optic neuritis, myasthenia gravis, adrenal insufficiency, hypothyroidism and/or hyperthyroidism, autoimmune thyroiditis, hypophysitis, multiple sclerosis, or sarcoidosis
NOTE: For questions related to the definition of autoimmune disorders, sites should contact the team per the study protocol
Any known acquired or congenital immune deficiency
History of chronic obstructive pulmonary disease (COPD)
History of significant pulmonary conditions
Unstable asthma (e.g., sudden acute attacks occurring without an obvious trigger) or asthma requiring
Daily steroid or long-acting beta-agonist prevention
Hospitalization in the 2 years prior to entry
A history of chronic congestive heart failure or other significant cardiac condition
Any active clinically significant medical condition that, in the opinion of the site investigator, would place the participant at increased risk
History of pneumonitis within the last 5 years prior to study entry
Retinopathy or uveitis within 180 days prior to study entry
Any acute or chronic psychiatric diagnoses that, in the opinion of the investigator, make the participant ineligible for participation
Any vaccination within 30 days prior to entry
NOTE: Individuals who require vaccination must delay screening for the study until 30 days after receiving the last injection
Human immunodeficiency virus (HIV) infection
Evidence of current (within 1 year prior to entry) Hepatitis delta virus (HDV) infection (HDV antibody positive)
Acute or serious illness, in the opinion of the site investigator, requiring systemic treatment and/or hospitalization within 30 days prior to study entry
Alpha-Fetoprotein (AFP) >100 within 42 days prior to study entry in the absence of imaging within the prior 6 months prior to study entry to exclude hepatocellular carcinoma (HCC)
Any known bleeding disorder (i.e., hemophilia)
Receipt of investigational drug or device within 6 months prior to study entry
History of treatment with a phosphoinositide 3-kinase inhibitor, including idelalisib
History of checkpoint inhibitor treatment including anti-programmed death-1 (anti-PD-1), anti-programmed death-ligand 1 (anti-PD-L1) or anti-cytotoxic T-lymphocyte antigen 4 (anti-CTLA-4) antibodies
History of immunoglobulin IgG therapy
Receipt of interferon (IFN) therapy within 12 months prior to study entry
Use of immunomodulators (e.g., interleukins, cyclosporine), systemic cytotoxic chemotherapy, or corticosteroid therapy
NOTE A: Participants receiving topical corticosteroids will not be excluded
NOTE B: Participants receiving inhaled corticosteroids will be excluded
Intent to use immunomodulators (e.g., IL-2, IL-12, interferon [IFNs], or TNF modifiers) or corticosteroids (other than topical steroids) during the course of the study
Current HCV antiviral therapy or receipt of HCV treatment in the 6 months prior to study entry
Use of anticoagulants within the 30 days prior to study entry
Prior treatment with other immune modulating agents that was associated with toxicity that resulted in discontinuation of the immune-modulating agent
Current use or intent to use biotin 5 mg/day, including within dietary supplements during the study
NOTE: Please see the study protocol for a list of other names used for biotin that should be looked for on the labels of dietary supplements
Positive thyroid peroxidase (TPO) antibody result within 42 days prior to study entry
Positive glutamic acid decarboxylase antibody (GAD65 Ab) result within 42 days prior to study entry
Positive islet cell antibody result within 42 days prior to study entry
Positive antinuclear antibody (ANA) 1:80 within 42 days prior to study entry
Anti-smooth muscle antibody >1:80 within 42 days prior to study entry
Immunoglobulin G (IgG) 1.2 x ULN within 42 days prior to study entry
Known allergy/sensitivity or any hypersensitivity to components of cemiplimab (anti-PD-1) or its formulation or previous mAb treatments
Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements
Breastfeeding or pregnancy
A male participant with a pregnant female sexual partner
For participants in the optional leukapheresis (LA) component, prior history of difficulty establishing venous access or current contraindication for LA, in the opinion of the site investigator and based on pre-LA assessments listed in the study protocol
NOTE: Participants unwilling or unable to complete LA are still eligible for enrollment into the main study
Participants with a history of solid organ transplant
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