A Randomized, Placebo-Controlled, Phase 2 Study of HB-101, a Bivalent Cytomegalovirus (CMV) Vaccine, in CMV-Seronegative Recipient (R-) Patients Awaiting Kidney Transplantation from Living CMV-Seropositive Donors (D+)
- Conditions
- Cytomegalovirusinfection10047438
- Registration Number
- NL-OMON48943
- Lead Sponsor
- Hookipa Biotech AG
- Brief Summary
Trial never started
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Withdrawn
- Sex
- Not specified
- Target Recruitment
- 22
English
1. Male or female patients 18 years of age or older.
2. Patients willing and able to give written informed consent for participation
in the study.
3. Patients must be eligible to undergo kidney transplantation from a
living donor as per institutional standards.
4. For Group 1 and 2, patients must be CMV immunoglobulin G (IgG) seronegative
(-) and will be
receiving kidney for transplantation from donors who are CMV IgG seropositive
(+). (If CMV IgG serology is indeterminate, repeat testing is recommended. If
the serology for the donor is indeterminate upon repeat testing, it should be
considered positive; if the serology for the
recipient is indeterminate upon repeat testing, it should be considered
negative).
5. For Group 3, patients must be CMV IgG seropositive (+) and will be receiving
a kidney for transplantation from donors who are CMV IgG seropositive (+) or
CMV IgG seronegative (-). Group 3 patients must have documentation of a planned
transplant that is scheduled to occur between 2 and 4 months after the first
study drug injection.
6. Post-transplant CMV management will follow either preemptive treatment
strategy (Group 1) or prophylactic anti-viral medication(s) (e.g.,
valganciclovir) per institutional standard of practice (Group 2).
7.Female patients of childbearing potential can participate in the study if
they agree to use highly effective contraception. This applies from the time
period between signing of the informed consent form and up to 12 months after
the last study drug (HB-101 or placebo) injection or up to completion of the
study, whichever is longer. Highly effective contraception methods include:
• Total abstinence.
• Male or female sterilization.
• Combination of any 2 of the following categories (Categories 1+2, 1+3,
or 2+3):
o Category 1: Use of oral, injected, or implanted hormonal methods of
contraception.
o Category 2: Placement of an intrauterine device or intrauterine system.
o Category 3: Barrier methods of contraception: condom or occlusive cap
(diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal
suppository.
8. Female patients must have a negative serum human chorionic gonadotropin
pregnancy test prior to each dose of study drug (HB-101 or placebo) unless the
pregnancy test is deemed a false positive and clinical evidence is negative for
pregnancy after discussion between the
sponsor and investigator on a case-by-case basis; or be surgically or
biologically sterile or menopausal.
Post-menopausal females are defined as:
• Age >50 years with amenorrhea for at least 12 months.
• Age <=50 years with 6 months of spontaneous amenorrhea and
follicle-stimulating hormone level within post-menopausal range (>40 mIU/mL).
• Permanently sterilized women (hysterectomy or bilateral oophorectomy).
9. Male patients with sexual partners of childbearing potential can
participate in the study if they agree to use barrier contraception from
the time period between signing of the informed consent form and
through 3 months after the last dose of study drug.
10. Male patients must agree to refrain from sperm donation from the time
period between signing of the informed consent form and through 3 months after
the last dose of study drug.
11. Patients who would comply with the requirements of this protocol
English
1. Patients who are highly sensitized or who are likely to undergo
desensitization at time of transplant (e.g., donor-specific antibody titers at
the local laboratory >2000).
2. Patients planning to undergo multi-organ transplantation.
3. Patients participating in another interventional clinical study.
4. Previous vaccination with an investigational CMV vaccine.
5. Patients with known diagnosis of human immunodeficiency virus.
6. Patients who are pregnant, breastfeeding, or planning to become pregnant
during the study.
7. Any Screening safety laboratory value of alanine aminotransferase (ALT) or
aspartate aminotransferase (AST) >5 X upper limit of normal (ULN), total
bilirubin >2 X ULN, absolute neutrophil count <500 cells/µL, or lymphocyte
count <200 cells/µL.
8. Any confirmed or suspected immunodeficiency disorder (based on medical
history and physical examination) that could interfere with the immune response
or that presents a risk for the patient to receive a vaccine candidate in
development.
9. Treatment with any chronic immunosuppressive medication or other immuno
modifying drugs within 6 months prior to study entry (unless agreed otherwise
between the sponsor and investigator on a case-by-case basis). However, inhaled
and topical steroids and low-dose oral corticosteroids
(<=10 mg milligrams a day of prednisone or equivalent) are allowed.
10. For Groups 1 and 2 only, patients with prior history of CMV disease or CMV
infection requiring anti-viral therapy.
11. For Group 3 only, patients with active CMV infection requiring antiviral
therapy within 30 days prior to the first injection of study drug.
12. Patients with a history of severe allergic reactions and/or anaphylaxis
that could interfere with the immune response (including an
allergy or hypersensitivity to any ingredient found in the study drug
[HB101 or placebo]) or that presents a risk for the patient to receive a
vaccine candidate in development.
13. Patients with a severe coagulation abnormality that would preclude
intramuscular injection.
14. Patients with a rash, dermatological condition, or tattoo in the area of
the injection site(s) that could interfere with administration site reaction
rating. (Note: The injection site(s) can be the non-dominant arm [most
preferred injection site], dominant arm, or either thigh [least preferred
injection site], as judged by the investigator).
15. History or current evidence of medical disorders or conditions that could
prevent the successful completion of the study, as judged by the investigator.
16. It is anticipated that the patient will be unavailable to complete study
follow-up.
17. Fever (>= 38°C) occurs within 7 days prior to first dose (unless agreed
otherwise between the sponsor and investigator on a case-by-case basis).
18. For patients in the post-transplant CMV prophylactic therapy management
group only, patients who will be receiving Cytogam® in their post-transplant
CMV prophylaxis regimen.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Safety and reactogenicity of HB-101 will be assessed by treatment group (for<br /><br>Groups 1 and 2 and open-label HB-101 for Group 3) and by number<br /><br>of vaccinations:<br /><br>(HB-101 versus placebo) and number of vaccinations:<br /><br>1.Incidence and severity of AEs, SAEs, and changes in laboratory values<br /><br>2.Incidence and severity of localized or generalized injection site reactions<br /><br>The immunogenicity of HB-101 will be assessed using descriptive central<br /><br>statistics presented by treatment group (for Groups 1 and 2 and open label<br /><br>HB-101 for Group 3) and by post-transplant CMV management strategy (prevention<br /><br>or preemption) for the following immunogenicity parameters:<br /><br>3.CMV neut<br /><br>4.CMV ELISPOT pp65<br /><br>5.CMV ELISPOT gB </p><br>
- Secondary Outcome Measures
Name Time Method <p>1.Incidence and time to clinically significant CMV infection, CMV disease, and<br /><br>CMV syndrome<br /><br>2.Incidence and time to CMV viremia requiring anti viral therapy<br /><br>3.Incidence and duration (in days) of anti-CMV therapy courses (at therapeutic<br /><br>doses) required<br /><br>4.Incidence and time to quantifiable CMV DNAemia, peak CMV DNAemia level, and<br /><br>duration of CMV DNAemia above the limit of quantitation<br /><br>5.Incidence and time to graft failure and organ rejection<br /><br>Additional immunogenicity parameters of HB-101 will be assessed using<br /><br>descriptive central statistics presented by treatment group for Group 1 and 2<br /><br>and open-label HB-101 for Group 3 and by post-transplant CMV management<br /><br>strategy (prevention or preemption) for the following immunogenicity parameters:<br /><br>6.LCMV neutralizing antibody<br /><br>7.CMV ICS pp65<br /><br>8.CMV ICS gB<br /><br>9.LCMV ELISPOT NP</p><br>