| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| no medical condition: healthy subjects |
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| MedDRA Classification |
| 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 |
Efficacy and Immunogenicity Objectives:
Primary:
To assess the efficacy (defined as prevention of HP infection) of Novartis’ HP vaccine candidate vs. placebo vaccine, as assessed by UGE (HP histopathology, HP culture and rapid urease test [RUT]) and non-invasive HP tests (urea breath test [UBT] and fecal antigen test) at 12 weeks following HP infectious challenge
Safety Objectives:
Primary:
To assess the tolerability of Novartis’ H. pylori (HP) vaccine vs. placebo vaccine. Measures to evaluate safety will include monitoring of local and systemic adverse events and clinical laboratory tests.
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| E.2.2 | Secondary objectives of the trial |
Efficacy and Immunogenicity Objectives:
Secondary:
• To determine the time course of HP infection following HP challenge of HP- vaccinated and placebo vaccinees, as assessed by UGE and non-invasive HP tests
• To define the humoral and cellular immune responses after HP vaccination and following subsequent infectious challenge with HP.
• To identify potential immune markers to distinguish HP vaccination from natural HP infection.
•To correlate mucosal and systemic cellular immune responses as assessed by sampling of gastric mucosa and peripheral blood cells, respectively
•To define potential immune correlates of protection (prophylactic efficacy).
Safety Objectives:
Secondary:
To assess gastrointestinal symptoms following HP challenge in HP-vaccinated and placebo vaccinees using the Gastrointestinal Symptom Rating Scale (GSRS) |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Inclusion Criteria:
Individuals eligible to be enrolled into this study are those:
1. who are 18 to 40 years of age and in good health as determined by the outcome of a medical history, physical examination and clinical judgment of the investigator
2. able to comprehend and follow all required study procedures
3. willing and able to sign an informed consent form
4. who are determined not to be HP infected based on the results of non-invasive testing (i.e. HP serological test, UBT, fecal antigen) and UGE
5. who have a negative urine pregnancy test and use of hormonal or barrier method of birth control (females of childbearing age) throughout the 12-month duration of the study
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| E.4 | Principal exclusion criteria |
Exclusion Criteria:
Individuals not eligible to be enrolled into this study are those who:
1. have household contact with children of age 2 or younger
2. have remote or current HP infection (as determined by HP serology, non-invasive HP testing, or by UGE)
3. have had major gastrointestinal surgery (e.g., other than appendectomy), documented peptic ulcer disease, gastrointestinal hemorrhage, gall bladder disease, inflammatory bowel disease, frequent diarrhea, or irritable bowel syndrome
4. have significant esophageal, gastric or duodenal pathology (gastric atrophy, dysplasia, or intestinal metaplasia ulcer or other abnormalities of the upper gastrointestinal tract) as determined by medical evaluation or UGE
5. have drug or alcohol dependence based on investigator clinical judgment
6. have significant acute or chronic medical or psychiatric illness
7. have any serious chronic or progressive disease (e.g., any history of neoplasm, diabetes, cardiac disease, autoimmune disease, HIV infection or AIDS, or blood dyscrasias, signs of cardiac or renal failure or severe malnutrition)
8. have a known or suspected disease of the immune system, or are receiving immunosuppressive therapy, including use of systemic corticosteroids or chronic use of inhaled high-potency corticosteroids within the previous 60 days
9. regular use of salicylates, nonsteroidal anti-inflammatory drugs, anticoagulants, or gold salts
10. have allergy or intolerance to aspirin, other salicylates, lidocaine, lansoprazole, omeprazole, H2-receptor antagonists, bismuth, metronidazole, tetracycline, penicillin, amoxicillin, or macrolide antibiotics or use of any of these agents within 4 weeks prior to study entry
11. have taken antibiotics within 7 days prior to enrollment or medical condition requiring the use of antibiotics during the course of the study
12. have a known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time
13. use of medications that may interact with bismuth, lansoprazole, omeprazole, amoxicillin, metronidazole, tetracycline, or macrolide antibiotics
14. have received another investigational agent within 90 days or before completion of the safety follow-up period in another study, whichever is longer, prior to enrollment and unwilling to refuse participation in another investigational trial through the end of the study
15. are pregnant or nursing mothers
16. have any other serious chronic disease including progressive neurological disease or seizure disorder
17. have received blood, blood products or a parenteral immunoglobulin preparation within the previous 60 days
18. have a history of severe allergic reactions after previous vaccinations, such as anaphylactic shock, asthma, urticaria, or other serious allergic reaction or hypersensitivity to any vaccine component requiring medical intervention
19. have either received, or for whom there is intent to immunize with any other vaccine(s) within 30 days prior, through 30 days following, study injection; exception: licensed flu-vaccine should not be administered within 14 days prior to enrollment but may be administered while on study if medically appropriate
20. have any condition which in the opinion of the investigator and/or the medical monitor that may interfere with the evaluation of the study objectives
21. work for or under the direct and full-time supervision of the Coordinating Investigator
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| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary endpoint of this investigation is the percentage of subjects with HP infection, using the appropriate case definition, at 3 months post challenge (Visit 10). The two vaccine groups (HP versus placebo) will be compared using a chi-square test for binomial proportions (arcsin approximation, 1-sided test) at significance level approximately equal to 0.05. With a sample size of 22 evaluable subjects in the placebo vaccine group and 30 subjects in the HP vaccine group, there is 98% power to detect a prophylactic efficacy of 50% assuming 90% infection rate in the placebo vaccine group, 91% power assuming 80% infection rate in the placebo vaccine group, and 82% power assuming 70% infection rate in the placebo vaccine group.
These endpoints formed the basis of the study design and the basis for the enrollment of the total number of subjects (n=63). As planned these subjects were randomized to receive either vaccine or placebo. Subjects were challenged in stages and following challenge of Stage 1B subjects the protocol required the DMC to assess the suitability of the challenge model. Since fewer than 50% of placebo subjects were found to be infected, per protocol the model was considered a challenge failure. Accordingly the DMC, the principal investigator and the sponsor all agreed that there was no benefit to challenge of Stage 2 subjects. However, the original study design and basis for enrollment of all study subjects is not changed by ending any further challenges. |
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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) | Yes |
| 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 | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
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| 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.8.3 |
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.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| 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
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | 14 |
| E.8.9.1 | In the Member State concerned days | |
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