Enhanced Epidermal Antigen Specific Immunotherapy Trial -1 (EE-ASI-1)
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|ClinicalTrials.gov Identifier: NCT02837094|
Recruitment Status : Recruiting
First Posted : July 19, 2016
Last Update Posted : June 12, 2017
The study is a two centre, open-label, uncontrolled single group phase 1A study of C19-A3 GNP peptide (10 μg peptide equivalent content) administered via Nanopass microneedles every 28 days for 8 weeks (3 doses), with follow-up for 6 weeks (14 weeks in total from first dose). Treatment will be given into the arm at a volume of 50ul.
No blinding or randomisation will be performed. In keeping with standard phase 1 study designs, no placebo or control group is included as the primary aim is to establish whether there are any major unexpected safety issues in the use of this IMP for the first time in man. 8 subjects will be recruited at 2 centres: Cardiff, UK and Linköping, Sweden.
|Condition or disease||Intervention/treatment||Phase|
|Type 1 Diabetes||Drug: C19-A3 GNP||Phase 1|
Type 1 Diabetes is caused by the body's own white blood cells damaging the insulin producing cells in the pancreas.
The aim is to develop a treatment that can slow or stop this process by switching off the white blood cells causing the damage. The aim of this study is to investigate whether giving such a treatment involving a peptide fragment related to insulin attached to gold nanoparticles is safe with no significant side-effects.
Participants need to be:
- Diagnosed with type 1 diabetes for more than 3 months.
- Aged between 18 and 40 years.
- Prescribed insulin within 1 month of diagnosis. 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 3 injections of the same treatment, these are given 4 weeks apart. During the treatment, participants will undergo various monitoring including blood & urine tests, mixed meal tolerance tests, lymph node biopsies. A follow up appointment will take place 6 weeks after the last injection. Possible side effects include bruising and discomfort at the site of the blood test and lymph node tests, local redness and swelling reactions at the site of the injections, severe allergic reaction to the injection requiring treatment, such as steroids, adrenaline or fluids.
Participants will have more time with staff members to discuss their diabetes and ask questions than at a routine clinic appointment. It is not known whether receiving the gold particle-peptide injections will be of benefit, as this is the first study where the treatment is being used in humans.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||8 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official 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|
|Study Start Date :||September 29, 2016|
|Estimated Primary Completion Date :||May 31, 2018|
|Estimated Study Completion Date :||December 31, 2018|
Experimental: C19-A3 GNP (Gold Nanoparticles)
C19A3 GNP intradermal microinjectable solution of human C19A3 proinsulin peptide coupled to gold. Solution For Injection The dose given will be equivalent to 10ug of C19A3 peptide at 3 dispensing visits, which are 4 weeks apart. Total 30ug.
|Drug: C19-A3 GNP|
- To examine the risk of C19A3 GNP administration in terms of general safety and induction of hypersensitivity. [ Time Frame: 4 months ]A physical examination will be conducted at screening and 0, 4, 8 and 14 weeks. A review of AEs will be performed at all visits and blood will be drawn at screening, weeks 4, 9, 14 & 20 to examine the full blood count; urea, electrolytes and creatinine; liver function tests; (prothrombin time, total bilirubin, total protein, albumin, AST (SGOT), SGPT (ALT), alkaline phosphatase; thyroid stimulating hormone; immunoglobulins (G, A, M); calcium; magnesium, phosphate, lipid profile (total cholesterol, LDL, HDL, triglyceride). Urinalysis for pH blood, protein, urine beta-2-microglobulin and albumin/creatinine ratio will be done at screening and visits 1, 2, 4, 5 and 6 and urine for cystatin-c will be collected at visits 1, 4, 5 & 6. A urine pregnancy test will be completed in females only, at all trial visits. Induction of hypersensitivity to C19-A3 GNP will be assessed by a period of observation of subjects and during the immediate period after peptide injection.
- To study the feasibility of delivering C19A3 GNP via microneedles to humans. [ Time Frame: 4 months ]By using the ultra short needles the antigen can be delivered into the superficial layers of the skin reliably with direct (perpendicular) injection. This approach has the advantage that it ensures intradermal rather than subcutaneous delivery ensuring high efficiency. At visits 1, 1b, 3b, 4, 5 and 6 blood and urine samples will be taken for gold concentrations to enable assessment of gold excretion.
- To study the immune responses to C19A3 GNP generated in blood. [ Time Frame: 4 months ]
Measured as follows:
T cell responses to C19-A3 GNP as determined by changes from baseline of interferon gamma following treatment.
- To study the immune responses to C19A3 GNP generated in the draining (axillary) lymph node. [ Time Frame: 4 months ]
Measured as follows:
T cell responses to C19-A3 GNP as determined by changes from baseline of interferon gamma in draining axillary lymph node before treatment and following the last treatment administration.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02837094
|Contact: Julie C Pell, PgC||+44 (0) email@example.com|
|Contact: Rachel Stenson, MSc||+44 (0) 29 firstname.lastname@example.org|
|Cardiff and Vale University Health Board||Recruiting|
|Cardiff, United Kingdom, CF14 4XW|
|Contact: Alexandra Howell +44 (0)29 20746710 ext 46710 HowellA4@cardiff.ac.uk|
|Study Director:||Colin M Dayan, MA FRCP PhD||Cardiff University|