| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Prevention of clinically significant cytomegalovirus (CMV) infection |
|
| E.1.1.1 | Medical condition in easily understood language |
| CMV can cause serious illness in people with weakened immune system (like cancer treatment, HIV, organ transplant) and can cause birth defects in the unborn child. |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10072247 |
| E.1.2 | Term | Cytomegalovirus immunisation |
| E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
1.To assess the safety and reactogenicity of HB-101.
2.To assess the immunogenicity of HB-101.
|
|
| E.2.2 | Secondary objectives of the trial |
1.To assess the efficacy of the administration of at least 2 doses of HB101 compared to that of placebo in mitigating CMV DNAemia/viremia CMV seronegative (-) recipients awaiting kidney transplantation from a CMV seropositive (+) donor and followed by CMV preemptive therapy post-transplant.
2.To assess the efficacy of the administration of at least 2 doses of HB101 compared to that of placebo in decreasing the use of anti-virals at treatment dose for CMV seronegative (-) recipients awaiting kidney transplantation from a CMV seropositive (+) donor and to be treated prophylactically
for CMV post transplant.
3.To assess the efficacy of the administration of at least 2 doses of HB101 in CMV seropositive (+) recipients awaiting kidney transplant and followed by CMV post transplant preemptive management or prophylactic
anti-viral therapy. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
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 (Group2).
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. Abstinence is acceptable only when this is in line with the preferred and usual lifestyle of the patient (e.g., true
abstinence). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
• 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 post 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
(e.g., return for follow up visits), as judged by the investigator.
|
|
| E.4 | Principal exclusion criteria |
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). Only patients with no risk or low risk of sensitization defined in the study protocol should be enrolled, owing to tolerance against the relevant HLA epitopes.
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 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 receiving the post-transplant CMV prophylactic therapy management group only, patients who will be receiving Cytogam® in their post-transplant CMV prophylaxis regimen. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Safety and reactogenicity of HB-101 will be assessed by treatment group (for Groups 1 and 2 and open-label HB-101 for Group 3) and by number of vaccinations:
1.Incidence and severity of AEs, SAEs, and changes in laboratory values
2.Incidence and severity of localized or generalized injection site reactions
The immunogenicity of HB-101 will be assessed using descriptive central statistics presented by treatment group (for Groups 1 and 2 and
openlabel HB-101 for Group 3) and by post-transplant CMV management strategy (prevention or preemption) for the following immunogenicity parameters:
3.CMV neut
4.CMV ELISPOT pp65
5.CMV ELISPOT gB |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. From the time of the first injection of study drug (HB-101 or placebo) up through 30 days after the last injection of study drug.
From 31 days after the last injection of study drug up through the End of Study Visit.
After transplant up to the End of the Study Visit.
Through the study
Until repeat test return to normal, stabilize, or are no longer clinically significant.
2.Prior to study drug administration on study drug dosing days
On treatment days for at least 60 minutes after study drug administration
3., 4. and 5.Each day of dosing, the day of the transplant and 3,6 and 9
months after the transplant, at the end of study visit. |
|
| E.5.2 | Secondary end point(s) |
1.Incidence and time to clinically significant CMV infection, CMV disease, and CMV syndrome
2.Incidence and time to CMV viremia requiring anti viral therapy
3.Incidence and duration (in days) of anti-CMV therapy courses (at therapeutic doses) required
4.Incidence and time to quantifiable CMV DNAemia, peak CMV DNAemia
level, and duration of CMV DNAemia above the limit of quantitation
5.Incidence and time to graft failure and organ rejection |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1., 2., 3., 4. and 5.Through 12 months after transplant
|
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | Yes |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 3 |
| E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 24 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| United States |
| Austria |
| Belgium |
| Denmark |
| France |
| Germany |
| Netherlands |
| Norway |
| Sweden |
| United Kingdom |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | 2 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 4 |
| E.8.9.2 | In all countries concerned by the trial months | 2 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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