Islet autoantigen-derived peptides eluted from Human Leucocyte Antigen (HLA) class II molecules as vaccines for the immunotherapy of type 1 diabetes: a safety and proof of concept study in man

ISRCTN	ISRCTN20254161
DOI	https://doi.org/10.1186/ISRCTN20254161
Protocol serial number	PI/1-s
Sponsor	Diabetes Vaccine Development Centre (Australia)
Funder	University of Melbourne (Australia) - Diabetes Vaccine Development Centre (protocol no: PI/1-S)

Submission date: 10/02/2006
Registration date: 03/03/2006
Last edited: 17/05/2011

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Nutritional, Metabolic, Endocrine

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Colin Dayan
Scientific

University of Bristol
Dorothy Hodgkin Building
Whitson street
Bristol
BS1 3NY
United Kingdom

Phone	+44 (0)117 9283553
Email	Colin.dayan@bristol.ac.uk

Study information

Primary study design	Interventional
Study design	Open label, phase 1, dose-escalating safety study with control (no treatment) arm (safety). T cell responses will also be measured (blinded) (proof of concept)
Secondary study design	Non randomised controlled trial
Scientific title
Study objectives	Type 1 diabetes mellitus is an autoimmune condition resulting in the destruction of pancreatic beta cells, leading to a failure of insulin production. Hypotheses: To determine in man whether intradermal administration of a soluble peptide sequence of proinsulin (C19-A3) identified by microelution from HLA-DR4 molecules and shown to be a disease-related T cell epitope by responses in newly-diagnosed patients with diabetes: 1. Is safe, particularly in terms of hypersensitivity reactions over a wide dose range (10 - 100 micrograms) (safety) 2. Can induce a regulated immune response in man (loss of peptide-specific interferon (IFN) gamma+ T cells, induction of peptide specific interleukin-10+ (IL-10+) T cells (proof of concept)
Ethics approval(s)	Central and South Bristol Research Ethics Committee on the 16/12/2005 (ref: 05/Q2006/55).
Health condition(s) or problem(s) studied	Type 1 diabetes mellitus
Intervention	A peptide corresponding to amino-acid C19-A3 of proinsulin will be administered in increasing doses, 10, 100 and 1000 micrograms intradermally in the upper arm. Subjects will be divided into three equal groups, one group for each dose of peptide. Beginning at 10 micrograms, injections will be given on three occasions one month apart before progressing to the next dose in a new group of subjects.
Intervention type	Drug
Phase	Phase I
Drug / device / biological / vaccine name(s)	Vaccine proinsulin (C19-A3)
Primary outcome measure(s)	1. Adverse event and side-effect profiles of peptide administration 2. Changes in proinsulin peptide-induced IFN-gamma+ or IL-10 response (ratio of maximal stimulation indices) as detected by Enzyme-Linked Immunosorbent Spot (ELISPOT) three months after the first injection compared to baseline
Key secondary outcome measure(s)	1. Change in proinsulin peptide induced IFN-gamma+ or IL-10 response ratio six months after the first injection 2. Changes in IFN-gamma+ or IL-10 response ratio to epitopes of GAD65 and IA-2 eluted from HLA-DR4 3. Changes in IL-2, IL-4+ and IL-5+ T cell responses to the antigen panel 4. Changes in anti-insulin, proinsulin, GAD65 and IA-2 antibody levels versus baseline
Completion date	31/12/2007

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	All
Target sample size at registration	72
Key inclusion criteria	1. HLA-DRB1 0401 positive patients 2. Aged 18 - 50 with type 1 diabetes of five or more years duration 3. HbA1c less than 10% and no insulin C-peptide production
Key exclusion criteria	1. C-peptide response to glucagon stimulation test greater than 2 nmol/l 2. Proliferative or pre-proliferative retinopathy or macula oedema 3. Diabetic nephropathy or other severe diabetic complications 4. Asthma 6. Atopy 7. Documented allergy 8. Use of steroids or immunosuppressive drugs 9. Other autoimmune diseases (except thyroiditis) 10. Women not taking effective contraception
Date of first enrolment	19/12/2005
Date of final enrolment	31/12/2007

Locations

Countries of recruitment

United Kingdom
England

Study participating centre

University of Bristol

Bristol
BS1 3NY
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/02/2009		Yes	No