Site Initiation Visit

Contents Overview Eligibility Identification Groups Exclusion Criteria Sample processing/labelling/shipment Supplies Using UK-AIH Guidance Manual Study Data to be sent to Newcastle Future of AIH Contacts

UK-AIH Overview Aim is to understand the unmet need in AIH and provide a platform for therapeutic advance Build a UK-wide cohort of people with AIH Target of 500 patients who will submit data and biological samples for deep phenotyping to identify markers of treatment response and prognosis & potential targets for future therapy Can enter the study via NUTH, their hospital consultant or independently

The criteria they meet will determine which group/cohort they fit into Eligibility All patients with a diagnosis of AIH can be taken into the UK-AIH Cohort if they are willing to take part in the study. The criteria they meet will determine which group/cohort they fit into

Identifying patients In clinic – give PIS and Participant Questionnaire (PQ). The patient can be consented into the study at the same clinic appointment, fill in the PQ and give bloods according to status.   Alternatively, the patient may consent, give blood and either bring the PQ back to the following clinic appointment or send it back in the post. Please ensure the UK-AIH number is on the PQ. If clinics can be screened beforehand, the PIS and PQ can be sent out to potential participants. This way they attend clinic fully informed and prepared to consent. Ward In Patients – we expect these to be primarily people admitted with suspected new diagnosis of AIH. Everything can be done for them while they are an IP.

Groups Group 1 Patients with a possible new diagnosis of AIH (Treatment Naïve) Patients with a possible new diagnosis of AIH Liver biopsy taken to confirm diagnosis then; 1. If histology verifies AIH- stay on Group 1 pathway (check inclusion & exclusion criteria) 2. If histology indeterminate but AIH is still suspected- Main Cohort or 3. If AIH is ruled out- discharge from study

Liver Biopsy Initial contact Give PIS Consent into the Study Tissue from liver biopsy – the research nurse will attend radiology with the participant. The sample will be no more than 0.2cm (at least 2cm should be left for diagnostic purposes). This is separated using a scalpel blade and then transferred to the cryovial pre filled with RNA-later (provided). Post the biopsy to Newcastle biobank in the mailer box (it can remain ambient for 1 week)  Await biopsy result to confirm diagnosis

Group 1 Visits, Bloods & CDF Visit 1 (before treatment) Participant given conformation of diagnosis ICF (V4-01/09/2014) - original in site file then 1 copy in notes and 1 copy to patient PQ part 1 only CDF - B completed by clinician Bloods – Serum, DNA, Peripheral blood cell RNA (2 tubes) Peripheral blood Immunophenotype: store at 4°C and courier overnight to Birmingham (contact Newcastle Biobank to arrange) Treatment starts today

Group 1 Visits, Bloods & CDF Visit 2 and 3 Visit 4 and 5 Visit 2 – 2 weeks (after starting treatment) CDF C completed by clinician Bloods – Serum and Peripheral blood cell RNA (1 tube) Visit 3 – 4 weeks (after starting treatment) Visit 4 - 4 months PQ part 2 CDF C completed by the clinician Bloods – Peripheral blood Thioguanine Nucliotide ((Aza mets) – 2 EDTA tubes) and Peripheral blood cell RNA (1 tube) (both taken only if taking Azathioprine or Mercaptopurine) Visit 5 - 8 months CDF C PQ part 2 only N.B. CDF C will need to be filled in at EVERY visit the patient has with the clinician throughout the first year Even if it is not a study visit

Group 1 Visits, Bloods & CDF Visit 6 (12months) PQ part 2 only CDF – D completed by the clinician Tissue sample (only if liver biopsy requested for clinical purposes – follow above directions) Bloods – Serum, Peripheral blood cell RNA (2 tubes) Peripheral blood Immunophenotype (2 EDTA tubes): store at 4°C and courier overnight to Birmingham (contact Newcastle Biobank to arrange)

Groups Group 2a (complete response) Group 2b (incomplete response) No steroids for at least 12 weeks ALT & IgG no higher than ULN Must have been diagnosed and on treatment for 1 year Group 2b (incomplete response) ALT higher than ULN or ALT no higher than ULN but daily prednisolone 10mg or higher (evidence of increased ALT if steroid dose reduced below 10mg) Clear evidence of patient developing Cirrhosis or Portal Hypertension since commencing continuous treatment Must have been diagnosed and on treatment for 1 year

Group 2a ICF - original in site file then 1 copy in notes and 1 copy to patient PQ- Part 1 & 2 CDF A- to be completed by the clinician Bloods- Serum & DNA Data Registration Form

Group 2b ICF – original in site file then 1 copy in notes and 1 copy to patient PQ Part 1 & 2 CDF A- to be completed by clinician Bloods- Serum & DNA Data Registration Form

Groups Main Cohort Patients under medical care for a diagnosis of AIH Must have been diagnosed and on treatment for 1 year Bloods or saliva for DNA optional Data Registration Form

Main Cohort ICF (V4-01/09/2014) – original in site file then 1 copy in notes and 1 copy to patient PQ - Part 1 & 2 CDF A - to be completed by clinician N.B. Bloods are optional in this Group- Serum & DNA

Exclusion Criteria Group 1, 2a & 2b Diagnosis of another liver disease including PBC, PSC and overlap Diagnosis of lymphoma, metastatic cancer, hepatocellular cancer, cholangiocarcinoma or pancreatic cancer Alcohol intake greater than recommended weekly intake Refer to Protocol and UK-AIH manual for in depth inclusion & exclusion criteria

Sample Processing Serum – 2 x 10ml SST Gold cap vacutainers – centrifuge at 3000rpm 10 mins and divide into 1ml aliquots (usually 5) – store at -80 then transfer to Newcastle biobank in batches via PDP* DNA – 1 x 5ml EDTA vacutainer (if signed consent part 3) this can be frozen at -80 and sent to Newcastle biobank in batches with Serum via PDP*

Sample Processing Peripheral blood cell RNA – 5ml Tempus RNA tubes (1 or 2) shake vigorously for 10 seconds – this can be frozen at -80 on site and sent to Newcastle biobank via PDP* in batches Peripheral blood thioguanine nucleotide (Aza Mets) – 2 x EDTA vacutainers (this is only to be taken if the patient is taking Azathioprine or Mercaptopurine) – post** to Newcastle biobank in mailer box provided. Contact Sally Coulthard with any queries via UK-AIH email Peripheral Blood Immunophenotype – 2 x 5ml EDTA purple cap vacutainer – All samples to be transferred to Birmingham using overnight shipping via PDP* Newcastle biobank will arrange.

Sample Pack Each site will get a sample pack on registering with the UK-AIH study, this will include stickers

Sample Labelling Each participant will be allocated a unique 6-digit number when she/he gives valid consent to participate in the study E.g., Subject Number: 01 0025 01-The first two digits identify the site at which recruitment took place (01 Newcastle, 02 Birmingham etc.) 0025-The next 4 digits are allocated to participants sequentially within the site. For instance, subject number 030034 is the 34th participant to give consent at site number 03 Site numbers are allocated as and when they join the study

Sample Labelling

Sample Labelling 3 sets of different coloured labels with same unique study number but different unique sample number Each sample will be labelled with a RED sticker with the UK-AIH participant number on it and the corresponding BLUE and BLACK stickers will be placed on the consent form and sample packing slip e.g.: RED = sample BLUE = consent form BLACK = sample packing slip See image on previous slide

Sample Shipment * Via PDP - Frozen samples transferred to Newcastle biobank via PDP – please call Karen Hedley at Newcastle biobank on 0191 2087855 and she will arrange this for you. *Via PDP - All samples for Birmingham via PDP, Newcastle biobank will also arrange – please call Karen Hedley 0191 2087855 ** Via Post - Posted samples will be sent in pre paid and addressed Blood Mailer Box provided (via hospital post room not in post box)

Supplies When running low on the list below, please contact the Newcastle BioBank on 0191 2087855 Addressed Mailers Sample labels Cryovials for serum Pre-filled RNA later cryovials for tissue Tempus RNA Tubes Cryovial freezer storage boxes (if needed)

Using the UK-AIH Guidance Manual Appendix 1 - Sample Packing Slip To be sent with all samples Circle group Place black stickers in appropriate box Document date of sample Document date and time of centrifugation Please keep a copy of this in the CRF Appendix 2 – to be printed onto research continuation sheet, completed and filed in patient’s notes Appendix 3 - detailed inclusion & exclusion criteria for reference

Study Documents to be sent to Newcastle Data to be sent to Newcastle on completion (copies): Consent form PQ CDF’s Registration Data Form Sample Packing Slip

Future of AIH Formic

Contacts UK-AIH email at uk-aih@newcastle.ac.uk Dr Emma Burton (Project Manager) emma.burton@ncl.ac.uk 0191 208 7744 Dr Jessica Dyson (PI) jessicadyson@doctors.org.uk Ms Kath Houghton (Lead Research Nurse) kathryn.houghton@ncl.ac.uk 0191 282 9885 Dr Amy Peasland (Biomedicine Central Biobank Manager) amy.peasland@newcastle.ac.uk 0191 282 4285 Karen Hedley (Biomedicine Assistant Newcastle BioBank) karen.hedley@newcastle.ac.uk 0191 208 7855 Dr Sally Coulthard - sally.coulthard@ncl.ac.uk