Enhanced Epidermal Antigen Specific Immunotherapy Trial -1

NCT02837094 | Completed Phase 1 DMC

• 1 other identifier: SPON1455-15
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

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.

Conditions

Type 1 Diabetes

Outcome Measures

Primary Outcomes (1)

• To examine the risk of C19A3 GNP administration in terms of general safety and induction of hypersensitivity.

  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.

  4 months

Secondary Outcomes (3)

• To study the feasibility of delivering C19A3 GNP via microneedles to humans.

  4 months

• To study the immune responses to C19A3 GNP generated in blood.

  4 months

• To study the immune responses to C19A3 GNP generated in the draining (axillary) lymph node.

  4 months

Study Arms (1)

Safety of C19A3 GNP (general safety and induction of hypersensitivity).

EXPERIMENTAL

To assess general safety different parameters were taken into account: A physical examination at screening and 0, 4, 8 and 14 weeks, a review of AEs at all visits and blood tests at screening, weeks 4, 9, 14 \& 20 for 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 at screening and visits 1, 2, 4, 5 and 6 and urine for cystatin-c was tested at visits 1, 4, 5 \& 6, a urine pregnancy test in females only, at all trial visits. Subjects were observed for systemic hypersensitivity to C19-A3 GNP during the immediate period after peptide injection.

Drug: C19-A3 GNP

Interventions

C19-A3 GNP DRUG

C19A3 GNP intradermal microinjectable solution of human C19A3 proinsulin peptide coupled to gold.

Also known as: Human C19A3 proinsulin peptide coupled to gold.

Safety of C19A3 GNP (general safety and induction of hypersensitivity).

Eligibility Criteria

• Age: 16 Years - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Clinical diagnosis of type 1 diabetes for \> 3 months (dated from the first insulin injection).
• Commenced on insulin treatment within 1 month of diagnosis.
• Age 16 to 40 years
• hour post-meal UCPCR \> 0.53 nmol/mmol on at least one occasion (maximum 3 tests on different days)
• Possession of 0401 allele at the HLA-DRB1 gene locus
• 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)

You may not qualify if:

• HbA1c \> 86mmol/L (10%).
• Females who are pregnant, breast-feeding or not using adequate forms of contraception.
• Previous diagnosis of renal disease including glomerulonephritis or nephropathy.
• 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).
• Use of cannabis within one month prior to trial entry.
• Use of any hypoglycaemia agents other than insulin, for more than 6 weeks, at any time prior to trial entry.
• Use of inhaled insulin.
• Known alcohol abuse, drug abuse, HIV or hepatitis.
• Allergies to drug components or any excipients.
• 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.
• 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
• 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.
• Abnormal ECG findings.

Sponsors & Collaborators

• Cardiff University: lead

Study Sites (1)

Cardiff and Vale University Health Board

Cardiff, CF14 4XW, United Kingdom

Location

Related Publications (1)

• Tatovic D, McAteer MA, Barry J, Barrientos A, Rodriguez Terradillos K, Perera I, Kochba E, Levin Y, Dul M, Coulman SA, Birchall JC, von Ruhland C, Howell A, Stenson R, Alhadj Ali M, Luzio SD, Dunseath G, Cheung WY, Holland G, May K, Ingram JR, Chowdhury MMU, Wong FS, Casas R, Dayan C, Ludvigsson J. Safety of the use of gold nanoparticles conjugated with proinsulin peptide and administered by hollow microneedles as an immunotherapy in type 1 diabetes. Immunother Adv. 2022 Jan 27;2(1):ltac002. doi: 10.1093/immadv/ltac002. eCollection 2022.

  PMID: 35919496 RESULT

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Colin M Dayan, MA FRCP PhD

  Cardiff University

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 4, 2016
• First Posted: July 19, 2016
• Study Start: September 29, 2016
• Primary Completion: December 31, 2019
• Study Completion: December 31, 2019
• Last Updated: March 31, 2023

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)