End Stage Renal Disease on Hemodialysis (Diagnosis)
Conditions
Keywords
ESRD, Hemodialysis, End Stage Renal Disease, Hepatitis B, HEPLISAV-B, Prevention and Control, HBV Vaccine, Hepatitis B Vaccine, HEPLISAV
Brief summary
This is an open-label, single arm study design to evaluate HEPLISAV-B® in adults with ESRD who are initiating or undergoing hemodialysis.
Detailed description
Eligible participants will receive single doses of HEPLISAV-B® at Weeks 0, 4, 8, and 16 and will be followed through Week 68 or end of study (EOS). The study is designed to evaluate the immunogenicity over a 20-week period and safety over a 68-week period.
Interventions
DRUGHEPLISAV-B®
HEPLISAV-B®, a licensed, commercially-available hepatitis B vaccine for adults 18 years of age and older, consisting of the adjuvant cytidine phosphoguanosine (CpG) 1018 combined with the antigen recombinant hepatitis B surface antigen (rHBsAg).
Sponsors
Dynavax Technologies Corporation
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male and female subjects at least 18 years of age * Laboratory confirmed negative serology result to hepatitis B virus (HBV) surface antigen (HBsAg), antibody to hepatitis B surface antigen (anti-HBs), and antibody to hepatitis B core antigen (anti-HBc) prior to first study injection * Must be clinically stable and in the opinion of the investigator able to comply with all study procedures * Must be able and willing to provide informed consent * Receiving hemodialysis or will initiate hemodialysis within 4 weeks of first study injection * Women of childbearing potential (WOCBP) must consistently use an acceptable method of contraception or confirm in writing she will abstain from sexual activity from the Screening visit through 4 weeks after the last dose of study injection. Acceptable birth control methods include but are not limited to oral contraceptive medication, an intrauterine device (IUD), an injectable contraceptive (such as medroxyprogesterone acetate or Depo-Provera®), a birth control patch, or a barrier method (such as condom or diaphragm with spermicide).
Exclusion criteria
* Previous receipt of any hepatitis B vaccine * History of human immunodeficiency virus (HIV) or hepatitis C virus (HCV) infection or antibody to HIV or HCV * History of sensitivity to any component of study vaccine * Substance or alcohol abuse that in the opinion of the investigator would interfere with compliance or with interpretation of the study results * Recent or ongoing history of febrile illness (within 7 days of the first study injection) * Has received any of the following prior to the first study injection: * Within 14 days: a. Any inactivated vaccine * Within 28 days: 1. Systemic corticosteroids (more than 3 consecutive days) or other immunomodulatory or immune suppressive medication with the exception of inhaled steroids 2. Any live virus vaccine 3. Granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) 4. Any other investigational medicinal agent * Within 90 days: 1. Blood products or immunoglobulin * If female and pregnant, nursing, or planning to become pregnant during the study * Undergoing chemotherapy or expected to receive chemotherapy during the study period * Has a medical condition considered by the investigator likely to interfere with the subject's compliance or the interpretation of study assessments, including the following laboratory abnormalities which the investigator may consider if severe: * Anemia * Thrombocytopenia * Leukocytosis * Neutropenia * Metabolic acidosis * Increased alanine aminotransferase (ALT) or aspartate aminotransferase (AST) * Hyperkalemia * Hypokalemia * Is scheduled to undergo a kidney transplant within 6 months of the first study injection
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects Reporting Clinically Significant Adverse Events - Medically-attended Adverse Events, Serious Adverse Events, and Immune-mediated Adverse Events of Special Interest | Week 0 (Visit 1) until Week 68 or early termination | Proportion of participants with Medically-attended adverse events (MAEs), Serious Adverse Events (SAEs), and immune-mediated Adverse Events of Special Interest (AESIs). MAEs are Adverse events (AEs) for which a subject sought medical attention at a doctor's office, clinic or study site, or emergency room, or was hospitalized. SAEs are AEs that met the definition of Serious per FDA regulations. |
| Seroprotection Rate (SPR) = Percentage of Participants Who Have a Seroprotective Immune Response | Week 20 | SPR is the percentage of participants who have a seroprotective immune response (antibody level to anti-HBsAg greater than or equal to 10 milli-international unit \[mIU\]/mL) after HEPLISAV-B |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects With Anti-HBs Concentration ≥100 mIU/mL | Weeks 4, 8, 16, 20 | Percentage of subjects with anti-HBs concentration ≥100 mIU/mL. |
| Serum Anti-HBsAg Geometric Mean Concentration (GMC) | Weeks 4, 8, 16, 20 | Serum Anti-HBsAg Geometric Mean Concentration (GMC). |
| Seroprotection Rate (SPR) = Percentage of Participants Who Have a Seroprotective Immune Response | Weeks 4, 8, 16, 20 | SPR is the percentage of participants who have a seroprotective immune response (antibody level to anti-HBsAg greater than or equal to 10 milli-international unit \[mIU\]/mL) after HEPLISAV-B |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| HEPLISAV-B® A single dose of 0.5 mL HEPLISAV-B® administered intramuscularly in the deltoid muscle at Week 0 (Visit 1), Week 4 (Visit 2), Week 8 (Visit 3), and Week 16 (Visit 4).
HEPLISAV-B®: HEPLISAV-B®, a licensed, commercially-available hepatitis B vaccine consisting of the adjuvant cytidine phosphoguanosine (CpG) 1018 combined with the antigen recombinant hepatitis B surface antigen (rHBsAg). | 119 |
| Total | 119 |
Baseline characteristics
| Characteristic | HEPLISAV-B® |
|---|---|
| Age, Continuous | 61.0 years |
| Age, Customized 18-55 | 47 Participants |
| Age, Customized 56+ | 72 Participants |
| Body Mass Index | 30.8 kg/m^2 STANDARD_DEVIATION 8.14 |
| Diabetes Mellitus Status No | 37 Participants |
| Diabetes Mellitus Status Yes | 82 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 22 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 97 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Height | 170.7 cm STANDARD_DEVIATION 10.39 |
| History of Hypertension No | 3 Participants |
| History of Hypertension Yes | 116 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 61 Participants |
| Race (NIH/OMB) More than one race | 7 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 51 Participants |
| Region of Enrollment United States | 119 participants |
| Sex: Female, Male Female | 47 Participants |
| Sex: Female, Male Male | 72 Participants |
| Smoking Status No | 95 Participants |
| Smoking Status Yes | 24 Participants |
| Weight | 89.9 kg STANDARD_DEVIATION 24.93 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 14 / 119 |
| other Total, other adverse events | 0 / 119 |
| serious Total, serious adverse events | 58 / 119 |
Outcome results
Primary
Percentage of Subjects Reporting Clinically Significant Adverse Events - Medically-attended Adverse Events, Serious Adverse Events, and Immune-mediated Adverse Events of Special Interest
Proportion of participants with Medically-attended adverse events (MAEs), Serious Adverse Events (SAEs), and immune-mediated Adverse Events of Special Interest (AESIs). MAEs are Adverse events (AEs) for which a subject sought medical attention at a doctor's office, clinic or study site, or emergency room, or was hospitalized. SAEs are AEs that met the definition of Serious per FDA regulations.
Time frame: Week 0 (Visit 1) until Week 68 or early termination
Population: Safety Population: All participants who received at least 1 study injection and who had any post-baseline safety data
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HEPLISAV-B | Percentage of Subjects Reporting Clinically Significant Adverse Events - Medically-attended Adverse Events, Serious Adverse Events, and Immune-mediated Adverse Events of Special Interest | New-onset Immune-mediated Adverse Events | 0.8 percentage of participants |
| HEPLISAV-B | Percentage of Subjects Reporting Clinically Significant Adverse Events - Medically-attended Adverse Events, Serious Adverse Events, and Immune-mediated Adverse Events of Special Interest | Medically-attended Adverse Events | 66.4 percentage of participants |
| HEPLISAV-B | Percentage of Subjects Reporting Clinically Significant Adverse Events - Medically-attended Adverse Events, Serious Adverse Events, and Immune-mediated Adverse Events of Special Interest | Serious Adverse Events | 48.7 percentage of participants |
Primary
Seroprotection Rate (SPR) = Percentage of Participants Who Have a Seroprotective Immune Response
SPR is the percentage of participants who have a seroprotective immune response (antibody level to anti-HBsAg greater than or equal to 10 milli-international unit \[mIU\]/mL) after HEPLISAV-B
Time frame: Week 20
Population: Per protocol subjects at Week 20
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HEPLISAV-B | Seroprotection Rate (SPR) = Percentage of Participants Who Have a Seroprotective Immune Response | 89.3 percentage of participants |
Secondary
Percentage of Subjects With Anti-HBs Concentration ≥100 mIU/mL
Percentage of subjects with anti-HBs concentration ≥100 mIU/mL.
Time frame: Weeks 4, 8, 16, 20
Population: Per protocol subjects at Weeks 4, 8,16, 20
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HEPLISAV-B | Percentage of Subjects With Anti-HBs Concentration ≥100 mIU/mL | Week 4 | 5.4 percentage of subjects with anti-HBs≥100 |
| HEPLISAV-B | Percentage of Subjects With Anti-HBs Concentration ≥100 mIU/mL | Week 8 | 33.8 percentage of subjects with anti-HBs≥100 |
| HEPLISAV-B | Percentage of Subjects With Anti-HBs Concentration ≥100 mIU/mL | Week 16 | 57.3 percentage of subjects with anti-HBs≥100 |
| HEPLISAV-B | Percentage of Subjects With Anti-HBs Concentration ≥100 mIU/mL | Week 20 | 81.3 percentage of subjects with anti-HBs≥100 |
Secondary
Seroprotection Rate (SPR) = Percentage of Participants Who Have a Seroprotective Immune Response
SPR is the percentage of participants who have a seroprotective immune response (antibody level to anti-HBsAg greater than or equal to 10 milli-international unit \[mIU\]/mL) after HEPLISAV-B
Time frame: Weeks 4, 8, 16, 20
Population: Per protocol subjects at Weeks 4, 8,16, 20
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HEPLISAV-B | Seroprotection Rate (SPR) = Percentage of Participants Who Have a Seroprotective Immune Response | Week 20 | 89.3 SPR percent (≥ 10 mIU/mL) |
| HEPLISAV-B | Seroprotection Rate (SPR) = Percentage of Participants Who Have a Seroprotective Immune Response | Week 4 | 20.3 SPR percent (≥ 10 mIU/mL) |
| HEPLISAV-B | Seroprotection Rate (SPR) = Percentage of Participants Who Have a Seroprotective Immune Response | Week 8 | 56.8 SPR percent (≥ 10 mIU/mL) |
| HEPLISAV-B | Seroprotection Rate (SPR) = Percentage of Participants Who Have a Seroprotective Immune Response | Week 16 | 78.7 SPR percent (≥ 10 mIU/mL) |
Secondary
Serum Anti-HBsAg Geometric Mean Concentration (GMC)
Serum Anti-HBsAg Geometric Mean Concentration (GMC).
Time frame: Weeks 4, 8, 16, 20
Population: Per protocol subjects at Week 4, 8, 16, 20
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| HEPLISAV-B | Serum Anti-HBsAg Geometric Mean Concentration (GMC) | Week 4 | 4.4 mIU/mL |
| HEPLISAV-B | Serum Anti-HBsAg Geometric Mean Concentration (GMC) | Week 8 | 33.5 mIU/mL |
| HEPLISAV-B | Serum Anti-HBsAg Geometric Mean Concentration (GMC) | Week 16 | 155.3 mIU/mL |
| HEPLISAV-B | Serum Anti-HBsAg Geometric Mean Concentration (GMC) | Week 20 | 1061.8 mIU/mL |