| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Prevention of Ebola virus disease |
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| E.1.1.1 | Medical condition in easily understood language |
| Prevention of Ebola virus disease |
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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 | 10014071 |
| E.1.2 | Term | Ebola disease |
| E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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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 tolerability of different vaccination schedules of Ad26.ZEBOV and MVA-BN-Filo administered intramuscularly (IM) as heterologous prime-boost regimens on Days 1 and 29, Days 1 and 57, or Days 1 and 85, in healthy adults, including elderly subjects, and on Days 1 and 29 and Days 1 and 57 in human immunodeficiency virus (HIV)-infected subjects and healthy children in 2 age strata. |
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| E.2.2 | Secondary objectives of the trial |
• To assess humoral immune responses, as measured by enzyme-linked immunosorbent assay (ELISA), to the Ebola virus glycoprotein (EBOV GP) at 21 days post boost of different vaccination schedules of Ad26.ZEBOV and MVA-BN-Filo administered IM as heterologous prime-boost regimens on Days 1 and 29, Days 1 and 57, or Days 1 and 85, in healthy adults, including elderly subjects, and on Days 1 and 29 and Days 1 and 57 in HIV-infected subjects and healthy children in 2 age strata.
• To assess the safety and tolerability of a third vaccination with Ad26.ZEBOV administered at least 1 year post prime in a subset of approximately 90 healthy adults, including elderly subjects, in Cohort 1 (Groups 1 and 2).
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| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
| At selected sites, approximately 90 healthy adult subjects in Cohort 1 (Groups 1 and 2) will receive a third vaccination with Ad26.ZEBOV or placebo at least 1 year post prime vaccination. |
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| E.3 | Principal inclusion criteria |
Inclusion Criteria for Healthy Adult and Elderly Subjects
1. Each subject must sign an ICF indicating that he or she understands the purpose of, and procedures required for, the study and is willing to participate in the study. In case the subject cannot read or write, the procedures must be explained and informed consent must be witnessed by a literate third party not involved with the conduct of the study.
2. Subject must be a man or woman aged 18 to 70 years of age, inclusive at randomization.
3. Subject must be healthy in the investigator’s clinical judgment on the basis of medical history, ECG, physical examination and vital signs performed at screening.
4. Subject must be healthy on the basis of clinical laboratory tests performed at screening.
5. Before randomization, a sexually active woman must be either:
- Of childbearing potential and practicing a highly effective method of birth control consistent with local regulations, beginning at least 28 days prior to vaccination, OR
- Not of childbearing potential: postmenopausal; permanently sterilized; or otherwise be incapable of pregnancy.
6. A woman of childbearing potential must have a negative serum β-human chorionic gonadotropin (β-hCG) pregnancy test at screening and a negative urine β-hCG pregnancy test immediately prior to each study vaccine administration.
7. A man who is sexually active with a woman of childbearing potential must be willing to use condoms for sexual intercourse beginning prior to enrollment, unless a vasectomy was performed more than 1 year prior to screening.
8. Subject must be available and willing to participate for the duration of the study visits and follow-up.
9. Subject must be willing and able to comply with the protocol requirements, including the Prohibitions and Restrictions specified in Section 4.3.
10. Subject must be willing to provide verifiable identification.
11. Subject must have a means to be contacted.
12. Subject must pass the test of understanding (TOU)
Additional Inclusion Criteria for HIV-infected Subjects
13. Subject must be a man or woman aged 18 to 50 years of age, inclusive at randomization.
14. Subject must have a documented HIV-infection for at least 6 months prior to screening.
15. Subject must be on a stable regimen of Highly Active Antiretroviral Therapy (HAART).
16. Subject must be in an otherwise reasonably good medical condition, diagnosed on the basis of physical examination, medical history and the investigator’s clinical judgment.
Inclusion Criteria for Pediatric Subjects
17. Parent(s)/legal guardian must have signed an ICF indicating that they understand the purpose of, and procedures required for, the study, are willing/able to adhere to the prohibitions and restrictions specified in the protocol and study procedures, and are willing for their child to participate in the study. Informed assent must be obtained from adolescents and older children, depending on local regulations and practice.
18. Subject must be male or female whose age on the day of randomization is within one of the 2 age strata in the study: 12-17 years or 4-11 years.
19. Subject must be healthy in the investigator’s clinical judgment (and the parent(s)/legal guardian) on the basis of medical history, physical examination and vital signs performed at screening.
20. Subject must be healthy on the basis of clinical laboratory tests performed at screening.
21. Before randomization, a female subject must be either:
- Of childbearing potential and practicing a highly effective method of birth control consistent with local regulations, beginning at least 28 days prior to vaccination; OR
- Not of childbearing potential: premenarchal.
22. A female subject of childbearing potential must have a negative serum β-hCG pregnancy test at screening and a negative urine β-hCG pregnancy test immediately prior to each study vaccine administration.
23. A male subject who is sexually active with a female subject of childbearing potential must be willing to use condoms for sexual intercourse beginning prior to enrollment.
24. Subject and parent(s)/legal guardian are available and willing to participate for the duration of the study visits and follow-up.
25. Subject and parent(s)/legal guardian must be willing and able to comply with the protocol requirements, including the Prohibitions and Restrictions specified in Section 4.3.
26. Subject and parent(s)/legal guardian must have a means to be contacted.
27. The parent(s)/legal guardian must pass the TOU. Older children and adolescents, who provided assent according to local regulations and practice, must also pass the TOU.
28. Subject has received all routine immunizations appropriate for his or her age as reported by the parent(s)/legal guardian, according to local routine vaccination schedules.
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| E.4 | Principal exclusion criteria |
Healthy Adult and Elderly Subjects
1. Has received any candidate Ebola vaccine.
2. Diagnosed with Ebola virus disease, or prior exposure to Ebola virus.
3. Has received any experimental candidate Ad26-or MVA-based vaccine in the past.
4. Known allergy or history of anaphylaxis or other serious adverse reactions to vaccines or vaccine products.
5. Subject with acute illness or body temperature ≥38.0° C on Day 1.
6. HIV type 1 or type 2 infection.
7. A woman who is pregnant, breast-feeding or planning to become pregnant while enrolled in the study or within at least 3 months after the prime vaccination, up to 1 month after the boost vaccination, or within at least 3 months after the third vaccination.
8. Presence of significant conditions or clinically significant findings during screening of medical history, ECG, physical examination, vital signs or laboratory testing for which participation would not be in the best interest of the subject.
9. History of or underlying liver or renal insufficiency, or significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric or metabolic disturbances.
10. History of malignancy other than squamous cell or basal cell skin cancer, unless there has been surgical excision that is considered cured.
11. Major surgery within the 4 weeks prior to screening or planned major surgery through the course of the study.
12. Post-organ and/or stem cell transplant whether or not with chronic immunosuppressive therapy.
13. Receipt of any disallowed therapies before the planned administration of the prime vaccine on Day 1.
14. Received an investigational drug/vaccine or used an invasive investigational medical device within 3 months prior to screening, or current or planned participation in another clinical study.
15. Donation of a unit of blood within 8 weeks before Day 1 or plans to donate blood until 42 days post-last vaccination.
16. Receipt of blood products or immunoglobulin within 3 months prior to screening and during the study.
17. Current or past abuse of alcohol, recreational or narcotic drugs, which in the investigator’s opinion would compromise the subject’s safety and/or compliance with the study procedures.
18. History of chronic urticaria.
19. Subject cannot communicate reliably with the investigator.
20. Subject who, in the opinion of the investigator, is unlikely to adhere to the requirements of the study.
21. Employee of the investigator or study site, with direct involvement in the proposed study or other studies under the direction of that investigator or study site, as well as family members of the employees or the investigator.
Additional Criteria for HIV-infected Subjects
Must not meet any of the exclusion criteria for healthy adult and elderly subjects with the exception of #6.
Pediatric Subjects
22. Has received any candidate Ebola vaccine.
23. Diagnosed with Ebola virus disease, or prior exposure to Ebola virus.
24. Has received any experimental candidate Ad26-or MVA-based vaccine in the past.
25. Known allergy or history of anaphylaxis or other serious adverse reactions to vaccines or vaccine products.
26. Subject with acute illness or body temperature ≥38.0ºC on Day 1.
27. HIV type 1 or type 2 infection.
28. A female subject who is pregnant, breast-feeding or planning to become pregnant while enrolled in the study or within 3 months after the prime vaccination or up to 1 month after the boost vaccination.
29. Weight-per-height below 10th percentile according to the CDC growth charts (4-11 year olds).
30. Presence of significant conditions or clinically significant findings during screening of medical history, physical examination, laboratory testing or vital signs for which participation would not be in the best interest of the subject.
31. History of or underlying liver or renal insufficiency, or significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric or metabolic disturbances.
32. Major congenital anomalies or known cytogenetic disorders.
33. Major surgery within the 4 weeks prior to screening or planned major surgery through the course of the study.
34. Receipt of any disallowed therapies before the planned administration of the prime vaccine on Day 1.
35. Received an investigational drug/vaccine or used an invasive investigational medical device within 3 months prior to screening, or current or planned participation in another clinical study.
36. Receipt of blood products or immunoglobulin within 3 months prior to screening and during the study.
37. History of chronic urticaria, eczema and/or atopic dermatitis.
38. Subject lives in an orphanage.
39. Subject’s parent(s)/legal guardian cannot communicate reliably with the investigator.
40. Subject or parent(s)/legal guardian who, in the opinion of the investigator, is unlikely to adhere to the requirements of the study. |
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| E.5 End points |
| E.5.1 | Primary end point(s) |
1. Adverse events, collected until the 42-day post-last vaccination (excluding third vaccination) visit.
2. Serious adverse events and immediate reportable events (IREs), collected from signing of the ICF onwards until the end of the study.
3. Solicited local and systemic adverse events (reactogenicity), collected until 7 days after each study vaccine administration.
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Until the 42-day post-last vaccination (excluding third vaccination) visit
2. From screening until the end of the study
3. Until 7 days after each study vaccine administration
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| E.5.2 | Secondary end point(s) |
1. Humoral immune response
- Binding antibody levels elicited by vaccination using EBOV GP ELISA at 21 days post boost.
2. Safety and tolerability (Cohort 1 substudy)
- Adverse events, collected from the day of the third vaccination onwards until 28 days thereafter.
- Serious adverse events and IREs, collected from signing of the original ICF onwards until the end of the study (including Cohort 1 substudy). |
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| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. At 21 days post boost vaccination
2 a). From the day of the third vaccination onwards until 28 days thereafter
2 b). From screening until the end of the study |
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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 | No |
| 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 | Yes |
| E.6.13.1 | Other scope of the trial description |
| Immunogenicity and tolerability |
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| 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 |
Will this trial be conducted at a single site globally?
| No |
| E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
| E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
| Burkina Faso |
| Côte d’Ivoire |
| Kenya |
| Uganda |
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| E.8.7 | Trial has a data monitoring committee | Yes |
| 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.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 4 |
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