Crohn's disease Digestive System
Conditions
Interventions
This is a phase I open-label dose escalation study to assess the safety and immunogenicity of the candidate Mycobacterium avium subspecies paratuberculosis (MAP) vaccine, ChAdOx2 HAV in patients with
Sponsors
HAV Vaccines Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age 18 to 50 years. 2. Confirmed diagnosis of Crohn’s disease diagnosed according to standard clinical, endoscopic, radiological or histological criteria. 3. Mild to moderately active Crohn’s inflammation as defined by one or more of a raised CRP >10mg/L, faecal calprotectin >150 and a CDAI >150 but <320. 4. Active Crohn’s inflammation in at least one segment of ileum or colon on colonoscopy or flexible sigmoidoscopy. 5. No immunomodulatory treatment (thiopurines, methotrexate, tacrolimus, anti-TNFalpha antibody therapy, anti-alpha4beta7 antibody therapy, anti-p40 antibody therapy) currently or within the last 3 months. 6. Able to comply with all study requirements. 7. For females only, willingness to practice continuous effective contraception (see below) during the study and a negative pregnancy test on the day(s) of screening and vaccination. 8. Agreement to refrain from blood donation during the course of the study. 9. Provide written informed consent.
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 18/11/2021: 1. Participation in another research study involving receipt of an investigational product in the 30 days preceding enrolment, or planned use during the study period. 2. Prior receipt of an investigational vaccine likely to impact on interpretation of the trial data. 3. Prior receipt of an adenoviral vectored vaccine in the last 28 days. 4. Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate. 5. Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV infection; asplenia; recurrent, severe infections. 6. Any immunosuppressive medication currently or within the preceding 3 months including corticosteroids (except inhaled steroid or topical steroid), thiopurines, methotrexate, tacrolimus and any biological therapy. 7. History of allergic disease or reactions likely to be exacerbated by any component of the vaccine (e.g. Egg allergy) 8. Any history of hereditary angioedema, acquired angioedema, or idiopathic angioedema. 9. Any history of anaphylaxis in relation to vaccination. 10. Unable to provide written informed consent. 11. Pregnancy, lactation or willingness/intention to become pregnant during the study. 12. History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ). 13. History of serious psychiatric condition likely to affect participation in the study. 14. Bleeding disorder (e.g. Factor deficiency, coagulopathy or platelet disorder), or prior history of significant bleeding or bruising following IM injections or venipuncture. 15. Any other serious chronic illness requiring hospital specialist supervision. 16. Suspected or known current alcohol abuse as defined by an alcohol intake of greater than 42 units every week. 17. Suspected or known injecting drug abuse in the 5 years preceding enrolment. 18. Seropositive for hepatitis C (antibodies to HCV). 19. Seropositive for hepatitis B surface antigen (HBsAg). 20. Any clinically significant abnormal finding on screening biochemistry or hematology blood tests or urinalysis. 21. Any other significant disease, disorder or finding which may significantly increase the risk to the participant _____ Previous exclusion criteria: 1. Participation in another research study involving receipt of an investigational product in the 30 days preceding enrolment, or planned use during the study period. 2. Prior receipt of an investigational vaccine likely to impact on interpretation of the trial data. 3. Prior receipt of an adenoviral vectored vaccine in the last 12 months. 4. Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate. 5. Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV infection; asplenia; recurrent, severe infections. 6. Any immunosuppressive medication currently or within the preceding 3 months including corticosteroids (except inhaled steroid or topical steroid), thiopurines, methotrexate, tacrolimus and any biological therapy. 7. History of allergic disease or reactions likely to be exacerbated by any component of the vaccine (e.g. Egg allergy) 8. Any history of hereditary angioedema, acquired angioedema, or idiopathic angioedema. 9. Any history of anaphylaxis in relation to vaccination. 10. Unable to provide written informed consent. 11. Pregnancy, lactation or
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Occurrence of solicited local reactogenicity signs and symptoms for 7 days following the vaccination 2. Occurrence of solicited systemic reactogenicity signs and symptoms for 7 days following the vaccination 3. Occurrence of unsolicited adverse events for 28 days following the vaccination 4. Change from baseline for safety laboratory measures 5. Occurrence of serious adverse events during the whole study duration | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. ELISPOT to enumerate IFN-? producing T cells. (Other exploratory immunology may be carried out in collaboration with other specialist laboratories. This would involve the transfer of serum/plasma and/or peripheral blood mononuclear cells (PBMC), but samples would be anonymised. Participants will be consented for this.) 2. Sampling of exploratory immunology responses: 50-60ml of whole blood will be taken at baseline and days 28 and 56 (groups 1 – 4) and additionally on days 14, 70, 84 and 112 (group 5 only) of the study for use in assays to measure immune responses of various types to the vaccine. 3. Assessment of clinical response All participants will undergo an evaluation of Crohn’s disease activity at screening and at day 56 for groups 1 – 4. Group 5 will undergo an evaluation of Crohn’s disease activity at screening, on day 56 and again on day 112. Endoscopic scoring by flexible sigmoidoscopy or colonoscopy will be undertaken by the CD-SES (simple endoscopic score) at the baseline and follow up at day 112. | — |
Countries
England, United Kingdom
Contacts
Public ContactPaul Ian;Jeremy Cross;Sanderson
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Outcome results
None listed