E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Prevention of clinically significant cytomegalovirus (CMV) infection |
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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. |
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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 | 20.0 |
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 |
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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 |
To assess the safety and reactogenicity of HB-101.
To assess the immunogenicity of HB-101 (immunogenicity parameters of CMV-neutralization [neut], CMV enzyme-linked immunospot [ELISPOT] phosphoprotein 65 kD [pp65], and CMV ELISPOT glycoprotein B [gB]).
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E.2.2 | Secondary objectives of the trial |
To assess the efficacy of the administration of at least 2 doses of HB-101 compared to that of placebo in mitigating CMV DNAemia/viremia.
To assess the efficacy of the administration of at least 2 doses of HB-101 compared to that of placebo in decreasing the use of anti-virals at treatment dose.
To assess additional immunogenicity parameters (including immunogenicity parameters of lymphocytic choriomeningitis virus [LCMV] neutralizing antibody, CMV intracellular cytokine staining [ICS] pp65, CMV ICS gB, and LCMV ELISPOT nucleoprotein [NP]).
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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. Patients must be CMV immunoglobulin G (IgG) seronegative (-) and 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. Group 1 only: Patient and investigator to use preemptive treatment strategy. 6. Group 2 only: Patient and investigator to use prophylactic pharmacological CMV prevention/prophylaxis (e.g., valganciclovir) after kidney transplantation. 7. Female patients who are sterile or post-menopausal can participate in the study. 8. 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. 9. Female patients must have a negative serum human chorionic gonadotrophin pregnancy test prior to each dose of study drug (HB-101 or placebo) 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). 10. 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. 11. 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. 12. Patients who would comply with the requirements of this protocol (e.g., return for follow up visits), as judged by the investigator.
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E.4 | Principal exclusion criteria |
1. Patients who are highly sensitized and/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 milligrams a day of prednisone or equivalent) are allowed. 10. Prior history of CMV disease or CMV infection requiring anti-viral therapy. 11. Patients with a history of severe allergic reactions and/or anaphylaxis that could interfere with the immune response or that presents a risk for the patient to receive a vaccine candidate in development. 12. Patients with a severe coagulation abnormality that would preclude intramuscular injection. 13. 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). 14. History or current evidence of medical disorders or conditions that could prevent the successful completion of the study, as judged by the investigator. 15. It is anticipated that the patient will be unavailable to complete study follow-up. 16. 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).
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Adverse events including clinical laboratory test variables (Complete Blood Count with differential, liver function tests and enzymes, renal function tests) 2. Adverse events considered by the investigator to be related to study drug 3. Adverse events of special interest post-transplant (graft rejection, CMV syndrome, CMV disease and autoimmune disease) 4. Physical examination and local assessment of the study drug (HB-10 or placebo) injection site 5. Clinically significant abnormal laboratory values occurring during the clinical study 6. Serious Adverse Events (SAEs) and pregnancies 7. Vitals signs (oral body temperature, heart rate, diastolic blood pressure, systolic blood pressure, and respiratory rate) 8. Potential general (malaise, fatigue, body temperature, generalize myalgia, nausea, vomiting, diarrhea, headache, myalgia, illness or clinical adverse event) and local signs/symptoms of reactogenicity (administration site pain/tenderness/induration/ erythema/redness/pruritus/swelling) 9. Cytomegalovirus serology 10. Transplant characteristics , including degree of human leukocyte antigen mismatch, use of induction therapy and nature, donor characteristics, warm ischemia time, cold ischemia time, laparoscopy, and kidney side. 11. Cellular immunogenicity analyses : - CMV pp65-specific interferon γ (IFN-γ) ELISPOT assay; (CMV ELISPOT pp65) - CMV gB-specific IFN-γ ELISPOT assay; (CMV ELISPOT gB) 12. Humoral immunogenicity analysis : - CMV-neutralization on MRC-5 cells; (CMV neut). |
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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. 2. From 31 days after the last injection of study drug up through the End of Study Visit. 3. After transplant up to the End of the Study Visit. 4. and 6.: Thorough the study 5. Until repeat test return to normal, stabilize, or are no longer clinically significant. 7. Prior to study drug administration on study drug dosing days 8. On treatment days for at least 60 minutes after study drug administration 9. During Screening up to 56 days prior to Day 0. 10. At the time of the transplant 11. and 12. Each day of dosing, the day of the transplant and 3,6 and 9 months after the transplant, at the end of study visit. |
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E.5.2 | Secondary end point(s) |
1. Incidence, magnitude, and duration of Cytomegalovirus viremia DNAemia 2. Incidence, duration, and number of courses of CMV anti-viral therapy 3. Cellular immunogenicity analyses : - CMV pp65-specific ICS of CD4+ and CD8+ T-cells for IFN-γ, interleukin-2 (IL-2), tumor necrosis factor alpha (TNF-α), CD107a, and CD40L; (CMV ICS pp65) - CMV gB-specific ICS of CD4+ and CD8+ T-cells for IFN-γ, IL-2, TNF-α, CD107a, and CD40L; (CMV ICS gB) - LCMV NP-specific IFN-γ ELISPOT assay (possible that analyses will not occur at all time points, e.g., insufficient volumes of blood); (LCMV ELISPOT NP). 4. Humoral immunogenicity analyses : - LCMV neutralization; (LCMV neut). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. and 2. Trough 12 months after transplant 3. Each day of dosing, the day of the transplant and 3,6 and 9 months after the transplant, at the end of study visit. For the LCMV NP-specific IFN-γ ELISPOT assay : possibility that analyses will not occur at all time points (e.g. insufficient volumes of blood) 4. Prior to the first dose of the study drug, the day of the transplant and at the end of study visit. |
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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 | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 15 |
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 |
Austria |
Belgium |
Denmark |
France |
Germany |
Netherlands |
Norway |
Sweden |
United Kingdom |
United States |
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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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
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 | 2 |
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 |