Type 1 DiabetesPhase 1EE-ASI-1NCT02837094
Enhanced Epidermal Antigen Specific Immunotherapy Trial -1
A Phase 1 study testing C19-A3 GNP in people with Type 1 Diabetes, run by Cardiff University at 1 site in United Kingdom.
Trial 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). Read more about this study
- Who is it for?
- Ages 16 to 40 years
- Conditions the study is for
- Type 1 Diabetes
- What is being tested?
- C19-A3 GNP
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 29 Sep 2016to 31 Dec 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 to 40 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
- 2 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]:
Show all 20Show fewer
- 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)
- Written and witnessed informed consent to participate.
Who cannot join
- 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 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.
- Use of cannabis within one month prior to trial entry.
Show all 14Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Cardiff and Vale University Health Board
Cardiff, CF14 4XW
About this study
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
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.
Read the 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:
- 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.
- Conditions
- Type 1 Diabetes
- Being tested
- C19-A3 GNP
- Medical subject headings
- Diabetes Mellitus, Type 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
C19-A3 GNPDrug
Also called Human C19A3 proinsulin peptide coupled to gold.
C19A3 GNP intradermal microinjectable solution of human C19A3 proinsulin peptide coupled to gold.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: C19-A3 GNP |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 4 months
Secondary outcomes (3)
To study the feasibility of delivering C19A3 GNP via microneedles to humans.
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.
Measured: 4 months
To study the immune responses to C19A3 GNP generated in blood.
Measured as follows:
T cell responses to C19-A3 GNP as determined by changes from baseline of interferon gamma following treatment.
Measured: 4 months
To study the immune responses to C19A3 GNP generated in the draining (axillary) lymph node.
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.
Measured: 4 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jul 2016 (estimated)
- Study start29 Sep 2016
- Primary completion31 Dec 2019
- Study completion31 Dec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Type 1 DiabetesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cardiff University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Colin M Dayan, MA FRCP PhD, Study director, Cardiff University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02837094
- Sponsor's protocol ID
- SPON1455-15
- Acronym
- EE-ASI-1
- Status last verified
- Jan 2021
- First submitted
- 4 Jul 2016
- Last updated
- 31 Mar 2023
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 35919496
Study at a glance
From the registry record, last updated by the sponsor on 31 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02837094
- Acronym / sponsor ID
- EE-ASI-1 / SPON1455-15
- Conditions
- Type 1 Diabetes
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Cardiff UniversityUniversity, hospital or other
- Study start
- 29 Sep 2016 (actual)
- Primary completion
- 31 Dec 2019 (actual)
- Study completion
- 31 Dec 2019 (actual)
- First posted
- 19 Jul 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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 design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Safety of C19A3 GNP (general safety and induction of hypersensitivity). | Experimental | Drug: C19-A3 GNPTo 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. |
Who may qualify
- Ages
- 16 to 40 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (20 listed)
- 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
- 2 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
Key exclusion criteria (14 listed)
- 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 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| C19-A3 GNPAlso: Human C19A3 proinsulin peptide coupled to gold.C19A3 GNP intradermal microinjectable solution of human C19A3 proinsulin peptide coupled to gold. | Drug | Safety of C19A3 GNP (general safety and induction of hypersensitivity). |
Primary outcome
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.
3 secondary outcomes
To study the feasibility of delivering C19A3 GNP via microneedles to humans.
Time frame: 4 months
To study the immune responses to C19A3 GNP generated in blood.
Time frame: 4 months
To study the immune responses to C19A3 GNP generated in the draining (axillary) lymph node.
Time frame: 4 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Mar 2023.
- Results publication: PubMed 35919496Tatovic 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.
- Individual participant dataSharing planned: No
Related trials for Type 1 Diabetes
Active, not recruitingPhase 3
Clinical Application of Stem Cell Educator Therapy in Type 1 Diabetes
Type 1 Diabetes
RecruitingObservational study
Study of High Density Lipoprotein Function in Type 1 Diabetic Patients With Nephropathy
Type 1 Diabetes
Active, not recruitingPhase 1/2
A First-In-Human Study of ARO-INHBE in Adults With Obesity With and Without Type 2 Diabetes Mellitus
Obesity
RecruitingPhase 3
A Study to Evaluate Effect of AZD6234 in Adult Participants With Obesity or Overweight With Weight-related Comorbidity Without Type 2 Diabetes Mellitus
Obesity or Overweight
Not yet recruitingPhase 1/2
Safety and Efficacy Evaluation of 4th Generation Safety-engineered CAR T Cells Targeting Sarcomas
Sarcoma, Osteoid Sarcoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Colin M Dayan, MA FRCP PhD study director
Cardiff University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing C19-A3 GNP in people with Type 1 Diabetes, run by Cardiff University at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To examine the risk of C19A3 GNP administration in terms of general safety and induction of hypersensitivity. (time frame: 4 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02837094, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Mar 2023.