World Health Organization site
Skip Navigation Links

Main
Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: ISRCTN
Last refreshed on: 22 August 2022
Main ID:  ISRCTN16067611
Date of registration: 06/09/2016
Prospective Registration: No
Primary sponsor: Cardiff University (UK)
Public title: Enhanced epidermal antigen specific immunotherapy trial - Type 1 Diabetes
Scientific title: Enhanced Epidermal Antigen Specific Immunotherapy trial -1 (EE-ASI-1): a Phase 1a study of gold nanoparticles administered intradermally by microneedles to deliver immunotherapy with a proinsulin derived peptide in Type 1 diabetes
Date of first enrolment: 01/08/2016
Target sample size: 8
Recruitment status: Completed
URL:  https://www.isrctn.com/ISRCTN16067611
Study type:  Interventional
Study design:  Non-randomised study (Prevention)  
Phase:  Phase I
Countries of recruitment
Sweden United Kingdom Wales
Contacts
Name: Rachel    Stenson
Address:  T1D UK Immunotherapy Research Consortium Manager Room 2TB2 165B, C2 Link I&I, School of Medicine Cardiff University Heath Park CF14 4XW Cardiff United Kingdom
Telephone: +44 (0)29 20742182
Email: StensonR@cardiff.ac.uk
Affiliation: 
Name: Colin    Dayan
Address:  Cardiff University School of Medicine Heath Park CF14 4XW Cardiff United Kingdom
Telephone: +44 (0)29 20742182
Email: DayanCM@cardiff.ac.uk
Affiliation: 
Key inclusion & exclusion criteria
Inclusion criteria:
1. Clinical diagnosis of type 1 diabetes for > 3 months (dated from the first insulin injection)
2. Commenced on insulin treatment within 1 month of diagnosis
3. Age 16 to 40 years
4. 2 hour post-meal UCPCR > 0.53 nmol/mmol on at least one occasion (maximum 3 tests on different days)
5. Possession of 0401 allele at the HLA-DRB1 gene locus
6. The following birth control methods should be used (considered highly effective with a failure rate of less than 1% per year when used consistently and correctly):
6.1. Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation:
6.1.1. Oral
6.1.2. Intravaginal
6.1.3. Transdermal
6.2. Progestogen-only hormonal contraception associated with inhibition of ovulation:
6.2.1. Oral
6.2.2. Injectable
6.2.3. Implantable
6.3. Intrauterine device (IUD)
6.4. Intrauterine hormone-releasing system ( IUS)
6.5. Bilateral tubal occlusion
6.6. Vasectomised partner (provided that the partner is the sole sexual partner of the trial participant and that medical assessment of azoospermia has been confirmed)
6.7. Sexual abstinence (defined as refraining from heterosexual intercourse during the duration of the trial)
7. Written and witnessed informed consent to participate

Exclusion criteria:
1. HbA1c > 86mmol/L (10%)
2. Females who are pregnant, breastfeeding or not using adequate forms of contraception
3. Previous diagnosis of renal disease including glomerulonephritis or nephropathy
4. Raised serum creatinine or abnormal urine albumin/creatinine ratio (ACR) (values above the laboratory reference range). If the initial ACR is raised, this should be repeated on two further occasions as first morning samples. The subject can be included if both of these samples are negative (within the reference range)
5. Use of immunosuppressive or immunomodulatory therapies, including systemic steroids within 1 month prior to receiving the IMP and any monoclonal antibody therapy given for any indication. Note that previous exposure to proinsulin peptide C19-A3 in a clinical trial is an exclusion criterion
6. Use of cannabis within one month prior to trial entry
7. Use of any hypoglycaemia agents other than insulin, for more than 6 weeks, at any time prior to trial entry
8. Use of inhaled insulin
9. Known alcohol abuse, drug abuse, HIV or hepatitis
10. Allergies to drug components or any excipients
11. Any other medical condition which, in the opinion of investigators, could affect the safety of the subject’s participation or outcomes of the study, including immunocompromised states and autoimmune conditions
12. Subjects should not have had immunisations (flu and others) for 1 month prior to trial entry and should not receive any during their time in the trial – see section 5.6
13. Recent subject’s involvement in other research studies which, in the opinion of investigators, may adversely affect the safety of the subjects or the results of the study
14. Abnormal ECG findings


Age minimum:
Age maximum:
Gender: Both
Health Condition(s) or Problem(s) studied
Type 1 diabetes
Nutritional, Metabolic, Endocrine
Type 1 diabetes mellitus
Intervention(s)

IMP: C19-A3 GNP (gold nanoparticles) injected by Nanopass microneedles

Participants will have a blood test to assess whether they have the right tissue type for the study. If suitable, they will be asked to attend their local research centre for a general examination and further blood and urine tests. If the participant still has some insulin response after the post meal urine test they will proceed to the first injection. Each participant will have three injections of the same treatment, these are given 4 weeks apart. During the treatment, participants will undergo various monitoring including blood and urine tests, mixed meal tolerance tests, lymph node biopsies. A follow-up appointment will take place 6 weeks after the last injection.
Primary Outcome(s)
The safety (adverse event) profile of the investigational agent. The following time points are set for evaluation of adverse event profiles, but pharmacovigilance data will be collected at times points in between if events arise: 2 hours, 4 weeks, 8 weeks and 14 weeks
Secondary Outcome(s)

1. T cell responses to GNP C19A3 as determined by changes from baseline of interferon gamma and IL10 ELISPOT responses to this peptide in blood following treatment at weeks 0, 8 and 14
2. T cell responses to GNP C19A3 as determined by changes from baseline of interferon gamma and IL10 ELISPOT responses to this peptide in draining axillary lymph node before and after the first and last treatment administration
3. Changes in additional immunological biomarkers (e.g. flow cytometry profiles, T reg assays, beta cell and T-cell cell-free DNA markers) from baseline at week 0, 8 and 14
4. Effects on residual cpeptide secretion at week 12 as compared to baseline as assessed by a mixed meal tolerance
test and a stimulated urine cpeptide test
5. Effects on glycaemic control assessed by blood sugar profiles and HbA1c at week 14 as compared to baseline
6. Questionnaires on quality of life and diabetes self-management at baseline and week 14
Secondary ID(s)
SPON1455-15
2015-003934-28
NCT02837094
Source(s) of Monetary Support
Seventh Framework Programme
Secondary Sponsor(s)
Ethics review
Status:
Approval date:
Contact:
London - City & East Research Ethics Committee, 04/03/2016, ref: 16/LO/0020
Results
Results available:
Date Posted:
Date Completed: 31/12/2019
URL:
Disclaimer: Trials posted on this search portal are not endorsed by WHO, but are provided as a service to our users. In no event shall the World Health Organization be liable for any damages arising from the use of the information linked to in this section. None of the information obtained through use of the search portal should in any way be used in clinical care without consulting a physician or licensed health professional. WHO is not responsible for the accuracy, completeness and/or use made of the content displayed for any trial record.
Copyright - World Health Organization - Version 3.6 - Version history