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Safety Study to Assess Whether Proinsulin Peptide Injections Can Slow or Stop the Body Damaging Its Own Insulin-making Cells in the Pancreas in Patients Newly Diagnosed With Type 1 Diabetes (MonoPepT1De)

Primary Purpose

Type 1 Diabetes

Status

Completed

Phase

Phase 1

Locations

United Kingdom

Study Type

Interventional

Intervention

Pro insulin peptide

Saline

About this trial

This is an interventional treatment trial for Type 1 Diabetes focused on measuring Diabetes

Eligibility Criteria

18 Years - 40 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Age 18-40 years.
If female, must be (as documented in patient notes):
- postmenopausal (at least 1 year without spontaneous menses)
- surgically sterile (tubal ligation or hysterectomy at least 6 months prior to enrolment)
- using acceptable contraception (e.g., oral, intramuscular, or implanted hormonal contraception) at least 3 months prior to enrolment
- have a sexual partner with non-reversed vasectomy (with confirmed azoospermia)
- be using 1 barrier method with the use of a spermicide(e.g., condom, diaphragm or cap)
- have placement of a intra-uterine device
If male, must be:
- using a barrier method of contraception (condom) with the use of a spermicide
- have a sexual partner using one of the methods in point 2 above or
- have a non-reversed vasectomy (with confirmed azoospermia),
Diagnosis of Type 1 diabetes within the last 100 days (dated from the first insulin injection).
Possession of *0401 allele at the HLA-DRB1 gene locus
At least one positive islet cell autoantibody (ie anti-GAD65, antibodies to insulinoma-associated antigen-2 (IA-2) or zinc transporter 8 (ZnT8)).
Peak insulin C-peptide >200 pmol/L (at any time point after stimulation with Mixed Meal Tolerance Test).
Written and witnessed informed consent to participate.

Exclusion Criteria:

Females who are pregnant, breast-feeding or not using adequate forms of contraception.
Use of immunosuppressive or immunomodulatory therapies, including systemic steroids within 1 month prior to randomisation and any monoclonal antibody therapy given for any indication.
Any other medical condition which, in the opinion of investigators, could affect the safety of the subject's participation.
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.
Subjects should not have had immunisations with live or killed vaccines or allergic desensitisation procedures less than 1 month prior to their first treatment.

Sites / Locations

Countess of Chester
Bristol Royal Infirmary
University Hospital of Wales
Guy's Hospital
Royal Victoria Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Placebo Comparator

Arm Label

Pro insulin peptide

Pro insulin peptide & saline

Saline

Arm Description

Patients will receive 10 micro gr of the peptide every 2 weeks (12 doses).

Patients will receive 10 micro gr of the peptide monthly (ever 4 weeks, 6 doses) and saline injections monthly alternating with the peptide (2 weeks interval between the drug and saline).

Patients will receive 0 micro gr of peptide, but have saline injections every 2 weeks (controls)

Outcomes

Primary Outcome Measures

Safety

To address the safety issue of whether, in patients with newly-diagnosed diabetes who still make some insulin, proinsulin peptide therapy adversely affects the rate of damage to the insulin making cells.

Secondary Outcome Measures

Allergy and hypersensitivity

To confirm that PI peptide treatment does not induce allergy or hypersensitivity and has a good safety profile in new-onset type 1 diabetes patients.

Safety of frequent dosing

To explore the safety of extending peptide treatment to more frequent dosing (2-weekly) and for a longer time period (6 months)

Protective effects of insulin preservation

To provide preliminary data on any protective effect on preservation of insulin production after 1 year of treatment

T cell (immune) response to islet cell antigens

To provide preliminary data on changes in the T cell (immune) response to islet cell antigens in newly-diagnosed patients following PI peptide treatment.

Full Information

NCT ID

NCT01536431

First Posted

February 14, 2012

Last Updated

July 27, 2015

Sponsor

Cardiff University

Collaborators

Diabetes Vaccine Development Centre, Juvenile Diabetes Research Foundation

1. Study Identification

Unique Protocol Identification Number

NCT01536431

Brief Title

Safety Study to Assess Whether Proinsulin Peptide Injections Can Slow or Stop the Body Damaging Its Own Insulin-making Cells in the Pancreas in Patients Newly Diagnosed With Type 1 Diabetes

Acronym

MonoPepT1De

Official Title

Phase 1b Study of Proinsulin (PI) Peptide Immunotherapy in New-Onset Type 1 Diabetes

Study Type

Interventional

2. Study Status

Record Verification Date

July 2015

Overall Recruitment Status

Completed

Study Start Date

January 2012 (undefined)

Primary Completion Date

February 2015 (Actual)

Study Completion Date

February 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Cardiff University

Collaborators

Diabetes Vaccine Development Centre, Juvenile Diabetes Research Foundation

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The purpose of this study is to address the safety issue of whether, in patients with newly-diagnosed diabetes who still make some insulin, proinsulin peptide therapy adversely affects the rate of damage to the insulin making cells.

Detailed Description

Type 1 Diabetes (also known as insulin-dependent diabetes) is caused by destruction of the insulin producing cells (Beta Cells) in the pancreas. Our group is interested in how this destruction could be stopped or reversed, as this may lead to development of a new generation of diabetes treatments which can prevent or slow down the damage, reducing or possibly even removing there need for insulin injections. In a previous study we examined the safety of our novel approach to this problem, proinsulin (PI) peptide immunotherapy, in longstanding diabetes patients (diagnosed more than 5 years before), and found it to be well tolerated and free of major hypersensitivity reactions. However, it remains theoretically possible that this form of immunotherapy could make the immune reaction to the insulin making cells worse rather than better. This cannot be studied directly in longstanding patients as they have no or almost no insulin making cells left. So,the principle objective of the current study is to address the safety issue of whether, in patients with newly-diagnosed diabetes who still make some insulin, proinsulin peptide therapy adversely affects the rate of damage to the insulin making cells.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Type 1 Diabetes

Keywords

Diabetes

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

27 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Pro insulin peptide

Arm Type

Experimental

Arm Description

Patients will receive 10 micro gr of the peptide every 2 weeks (12 doses).

Arm Title

Pro insulin peptide & saline

Arm Type

Active Comparator

Arm Description

Patients will receive 10 micro gr of the peptide monthly (ever 4 weeks, 6 doses) and saline injections monthly alternating with the peptide (2 weeks interval between the drug and saline).

Arm Title

Saline

Arm Type

Placebo Comparator

Arm Description

Patients will receive 0 micro gr of peptide, but have saline injections every 2 weeks (controls)

Intervention Type

Drug

Intervention Name(s)

Pro insulin peptide

Intervention Description

Patients will receive 10 micro gr of the peptide every 2 weeks (12 doses).

Intervention Type

Drug

Intervention Name(s)

Pro insulin peptide

Intervention Description

Patients will receive 10 micro gr of the peptide monthly (ever 4 weeks, 6 doses) and saline injections monthly alternating with the peptide (2 weeks interval between the drug and saline).

Intervention Type

Drug

Intervention Name(s)

Saline

Intervention Description

Patients will receive 0 micro gr of peptide, but have saline injections every 2 weeks (controls).

Primary Outcome Measure Information:

Title

Safety

Description

Time Frame

3 years

Secondary Outcome Measure Information:

Title

Allergy and hypersensitivity

Description

To confirm that PI peptide treatment does not induce allergy or hypersensitivity and has a good safety profile in new-onset type 1 diabetes patients.

Time Frame

3 years

Title

Safety of frequent dosing

Description

To explore the safety of extending peptide treatment to more frequent dosing (2-weekly) and for a longer time period (6 months)

Time Frame

3 years

Title

Protective effects of insulin preservation

Description

To provide preliminary data on any protective effect on preservation of insulin production after 1 year of treatment

Time Frame

3 years

Title

T cell (immune) response to islet cell antigens

Description

To provide preliminary data on changes in the T cell (immune) response to islet cell antigens in newly-diagnosed patients following PI peptide treatment.

Time Frame

3 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

40 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Age 18-40 years. If female, must be (as documented in patient notes): postmenopausal (at least 1 year without spontaneous menses) surgically sterile (tubal ligation or hysterectomy at least 6 months prior to enrolment) using acceptable contraception (e.g., oral, intramuscular, or implanted hormonal contraception) at least 3 months prior to enrolment have a sexual partner with non-reversed vasectomy (with confirmed azoospermia) be using 1 barrier method with the use of a spermicide(e.g., condom, diaphragm or cap) have placement of a intra-uterine device If male, must be: using a barrier method of contraception (condom) with the use of a spermicide have a sexual partner using one of the methods in point 2 above or have a non-reversed vasectomy (with confirmed azoospermia), Diagnosis of Type 1 diabetes within the last 100 days (dated from the first insulin injection). Possession of *0401 allele at the HLA-DRB1 gene locus At least one positive islet cell autoantibody (ie anti-GAD65, antibodies to insulinoma-associated antigen-2 (IA-2) or zinc transporter 8 (ZnT8)). Peak insulin C-peptide >200 pmol/L (at any time point after stimulation with Mixed Meal Tolerance Test). Written and witnessed informed consent to participate. Exclusion Criteria: Females who are pregnant, breast-feeding or not using adequate forms of contraception. Use of immunosuppressive or immunomodulatory therapies, including systemic steroids within 1 month prior to randomisation and any monoclonal antibody therapy given for any indication. Any other medical condition which, in the opinion of investigators, could affect the safety of the subject's participation. 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. Subjects should not have had immunisations with live or killed vaccines or allergic desensitisation procedures less than 1 month prior to their first treatment.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Mark Peakman, MBBS BSc MSc PhD FRCP

Organizational Affiliation

King's College Hospital NHS Trust

Official's Role

Study Director

Facility Information:

Facility Name

Countess of Chester

City

Chester

State/Province

England

ZIP/Postal Code

CH2 1UL

Country

United Kingdom

Facility Name

Bristol Royal Infirmary

City

Bristol

Country

United Kingdom

Facility Name

University Hospital of Wales

City

Cardiff

Country

United Kingdom

Facility Name

Guy's Hospital

City

London

Country

United Kingdom

Facility Name

Royal Victoria Hospital

City

Newcastle

Country

United Kingdom

12. IPD Sharing Statement

Learn more about this trial

Safety Study to Assess Whether Proinsulin Peptide Injections Can Slow or Stop the Body Damaging Its Own Insulin-making Cells in the Pancreas in Patients Newly Diagnosed With Type 1 Diabetes

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