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Enhanced Epidermal Antigen Specific Immunotherapy Trial -1 (EE-ASI-1)

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ClinicalTrials.gov Identifier: NCT02837094
Recruitment Status : Unknown
Verified May 2019 by Cardiff University.
Recruitment status was:  Active, not recruiting
First Posted : July 19, 2016
Last Update Posted : May 16, 2019
Sponsor:
Information provided by (Responsible Party):
Cardiff University

Tracking Information
First Submitted Date  ICMJE July 4, 2016
First Posted Date  ICMJE July 19, 2016
Last Update Posted Date May 16, 2019
Study Start Date  ICMJE September 29, 2016
Estimated Primary Completion Date January 31, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 18, 2016)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 18, 2016)
  • 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Enhanced Epidermal Antigen Specific Immunotherapy Trial -1
Official Title  ICMJE 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
Brief Summary

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.

Detailed Description

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:

  1. Diagnosed with type 1 diabetes for more than 3 months.
  2. Aged between 18 and 40 years.
  3. 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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE Type 1 Diabetes
Intervention  ICMJE Drug: C19-A3 GNP
C19A3 GNP intradermal microinjectable solution of human C19A3 proinsulin peptide coupled to gold.
Other Name: Human C19A3 proinsulin peptide coupled to gold.
Study Arms  ICMJE 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.
Intervention: Drug: C19-A3 GNP
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: July 18, 2016)
8
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 31, 2020
Estimated Primary Completion Date January 31, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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]:

    • combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation:

      • oral
      • intravaginal
      • transdermal
    • progestogen-only hormonal contraception associated with inhibition of ovulation:

      • oral
      • injectable
      • implantable
    • intrauterine device (IUD)
    • intrauterine hormone-releasing system (IUS)
    • bilateral tubal occlusion
    • vasectomised partner (provided that the partner is the sole sexual partner of the trial participant and that medical assessment of azoospermia has been confirmed)
    • Sexual abstinence (defined as refraining from hetrosexual 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, breast-feeding 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
  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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 16 Years to 40 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02837094
Other Study ID Numbers  ICMJE SPON1455-15
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Cardiff University
Study Sponsor  ICMJE Cardiff University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Colin M Dayan, MA FRCP PhD Cardiff University
PRS Account Cardiff University
Verification Date May 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP