search
Back to results

MER3101: MAS-1 Adjuvanted Antigen-specific Immunotherapeutic for Prevention and Treatment of Type 1 Diabetes (MER3101)

Primary Purpose

Type 1 Diabetes Mellitus

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
MAS-1 adjuvanted Insulin B-chain
Sponsored by
University of Colorado, Denver
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

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

Eligibility Criteria

18 Years - 45 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Be between the ages of 18 and 45 years of age who meet the ADA standard T1DM criteria and are positive for at least 1 islet cell autoantibody.
  2. Type 1-diabetes mellitus diagnosed within the previous 2 years
  3. Must have stimulated C-peptide levels ≥ 0.2 pmol/ml measured during a mixed meal tolerance test (MMTT) conducted at least 21 days from diagnosis of diabetes and within one month (37 days) of randomization
  4. At least one month from last immunization
  5. Must be willing to comply with intensive diabetes management
  6. If participant is female with reproductive potential, she must have a negative pregnancy test and be willing to avoid pregnancy during the treatment period until 2 months after the last study drug administration.
  7. Willing to forgo routine clinical immunizations during the first 100 days after initial study drug administration (COVID-19 vaccination is permitted 60 days following initial study drug administration)
  8. Subjects must have HbA1c levels under 9.5 to be enrolled in the study.
  9. At least 30 days from receiving a single dose COVID-19 vaccine or at least 30 days from completing a multi-dose COVID-19 vaccine series.

Exclusion Criteria:

  1. Be currently pregnant or lactating, or anticipate getting pregnant during the treatment period until 2 months after the last study drug administration.
  2. Ongoing use of medications known to influence glucose tolerance
  3. Require use of systemic immunosuppressant(s)
  4. Any significant diabetes complications such as renal disease (proteinuria or elevated Cr) and diabetic retinopathy
  5. Have a history of malignancies
  6. Be currently using non-insulin pharmaceuticals to affect glycemic control
  7. Have any acute or chronic complicating medical issues or abnormal clinical laboratory results that interfere with study conduct or cause increased risk including neurological abnormalities.
  8. Inability or unwillingness to comply with the provisions of this protocol
  9. Have an active infection or positive tuberculosis test result.
  10. Have serologic evidence of current or past HIV, Hep B, or Hep C infection.
  11. Have a known history of hypersensitivity or allergy reactions to squalane or squalene based adjuvants or other components of the study immunogen
  12. Subjects with a history or evidence of chronic kidney disease (serum creatinine> 1.5mg/dL)
  13. Subjects with a history of proliferative diabetic retinopathy that has not been treated with laser therapy
  14. Subjects with a history of neuropathy, foot ulcers, amputations, or kidney disease
  15. Males of reproductive potential who are unwilling to use acceptable birth control during the treatment period through 2 months after the last study drug administration, unless the female partner is postmenopausal or surgically sterile.
  16. Have current, confirmed COVID-19 infection

Sites / Locations

  • University of Colorado, DenverRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Other

Other

Other

Other

Arm Label

33 ug IBC in 0.25 mL MAS-1 emulsion

109 ug IBC in 0.25 mL MAS-1 emulsion

327 ug IBC in 0.25 mL MAS-1 emulsion

TBD ug IBC in 0.5 mL MAS-1 emulsion

Arm Description

7 participants to be randomized between placebo and MAS-1 adjuvanted insulin B-chain (2:5) with a 33 ug IBC dose in 0.25 mL MAS-1 emulsion

7 participants to be randomized between placebo and MAS-1 adjuvanted insulin B-chain (2:5) with a 109 ug IBC dose in 0.25 mL MAS-1 emulsion

7 participants to be randomized between placebo and MAS-1 adjuvanted insulin B-chain (2:5) with a 327 ug IBC dose in 0.25 mL MAS-1 emulsion

7 participants to be randomized between placebo and MAS-1 adjuvanted insulin B-chain (2:5) with the maximum safe IBC dose selected from the first 3 groups (either 33 µg, or 109 µg, or 327 µg IBC) in 0.5 mL MAS-1 emulsion

Outcomes

Primary Outcome Measures

Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Number of participants with Treatment-Related Adverse Events, and the frequency of Adverse Events, as Assessed by CTCAE v4.0. The rates of severe hypoglycemic and adverse events will be computed (total number of events divided by total patient years of follow-up) and the rates compared using a Poisson regression model.
Immunologic Analysis
T cell assays looking for IL-4, IL-5, IL-10, IL-13, TGFβ production and shift towards Treg and iNKT cell population.

Secondary Outcome Measures

Mean C-peptide AUC value
The area under the stimulated C-peptide curve (AUC) over the first 2 hours of a mixed meal glucose tolerance test. The AUC is computed using the trapezoidal rule that is a weighted sum of the C-peptide values over the 120 minutes.
HbA1c value
The mean HbA1c over all follow-up values will be compared between the control and placebo group using a normal errors longitudinal analysis.
Insulin Use
The mean insulin dose (units/kg) over all follow-up values will be compared between the control and placebo group using a normal errors longitudinal analysis.

Full Information

First Posted
July 23, 2018
Last Updated
June 12, 2023
Sponsor
University of Colorado, Denver
Collaborators
The Leona M. and Harry B. Helmsley Charitable Trust, Nova Immunotherapeutics Limited
search

1. Study Identification

Unique Protocol Identification Number
NCT03624062
Brief Title
MER3101: MAS-1 Adjuvanted Antigen-specific Immunotherapeutic for Prevention and Treatment of Type 1 Diabetes
Acronym
MER3101
Official Title
MER3101: MAS-1 Adjuvanted Antigen-specific Immunotherapeutic for Prevention and Treatment of Type 1 Diabetes
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 31, 2020 (Actual)
Primary Completion Date
May 4, 2024 (Anticipated)
Study Completion Date
May 10, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Colorado, Denver
Collaborators
The Leona M. and Harry B. Helmsley Charitable Trust, Nova Immunotherapeutics Limited

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The study is a randomized, double-masked, placebo-controlled, Phase 1 dose-escalation clinical trial. The objective of the trial is to determine if IBC adjuvanted with MAS-1 is safe and will favor tolerogenic pathways to restore immunologic balance and reverse T1D autoimmunity.
Detailed Description
In this four-arm (cohort) study, subjects (5 active MER3101 per arm plus 2 MAS-1 placebo) will be randomized to receive two intramuscular doses at days 1 and 28. Subjects will receive either MAS-1 placebo emulsion, or MAS-1 adjuvanted IBC at 33, 109 and 327 µg IBC in 0.25 mL MAS-1 adjuvanted emulsion, followed by an additional arm to receive the maximum safe IBC dose selected from the first 3 arms in an increased dose volume of 0.5 mL MAS-1 emulsion and 2 subjects to receive 0.5 mL MAS-1 placebo control emulsion. All groups will receive standard intensive diabetes treatment with insulin and dietary management. The primary endpoint is to assess the safety and tolerability of 3 doses of progressively higher IBC antigen doses of the vaccine, and at 2 dose volumes (0.25 and 0.5 mL) of MAS-1 adjuvant emulsion at the maximum safe dose of IBC antigen. In addition, to determine if the vaccine induces a shift towards protection shown by increased levels of IL-4, IL-5, IL-10 and TGF-b and regulatory changes in insulin-specific T and B cells using novel reagents to detect these unique populations of cells in treated subjects.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 1 Diabetes Mellitus
Keywords
New onset

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
28 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
33 ug IBC in 0.25 mL MAS-1 emulsion
Arm Type
Other
Arm Description
7 participants to be randomized between placebo and MAS-1 adjuvanted insulin B-chain (2:5) with a 33 ug IBC dose in 0.25 mL MAS-1 emulsion
Arm Title
109 ug IBC in 0.25 mL MAS-1 emulsion
Arm Type
Other
Arm Description
7 participants to be randomized between placebo and MAS-1 adjuvanted insulin B-chain (2:5) with a 109 ug IBC dose in 0.25 mL MAS-1 emulsion
Arm Title
327 ug IBC in 0.25 mL MAS-1 emulsion
Arm Type
Other
Arm Description
7 participants to be randomized between placebo and MAS-1 adjuvanted insulin B-chain (2:5) with a 327 ug IBC dose in 0.25 mL MAS-1 emulsion
Arm Title
TBD ug IBC in 0.5 mL MAS-1 emulsion
Arm Type
Other
Arm Description
7 participants to be randomized between placebo and MAS-1 adjuvanted insulin B-chain (2:5) with the maximum safe IBC dose selected from the first 3 groups (either 33 µg, or 109 µg, or 327 µg IBC) in 0.5 mL MAS-1 emulsion
Intervention Type
Drug
Intervention Name(s)
MAS-1 adjuvanted Insulin B-chain
Intervention Description
MER3101 (MAS-1 adjuvanted insulin B chain (IBC)), is a white, free-flowing 30:70 (w/w) water-in-oil (W/O) emulsion. MER3101 contains in the aqueous (disperse) phase 33, 109, or 327 µg per 0.25 mL dose of IBC (Drug Substance) and the oil (continuous) phase is comprised of MAS-1 oil vehicle.
Primary Outcome Measure Information:
Title
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Description
Number of participants with Treatment-Related Adverse Events, and the frequency of Adverse Events, as Assessed by CTCAE v4.0. The rates of severe hypoglycemic and adverse events will be computed (total number of events divided by total patient years of follow-up) and the rates compared using a Poisson regression model.
Time Frame
43 months
Title
Immunologic Analysis
Description
T cell assays looking for IL-4, IL-5, IL-10, IL-13, TGFβ production and shift towards Treg and iNKT cell population.
Time Frame
43 months
Secondary Outcome Measure Information:
Title
Mean C-peptide AUC value
Description
The area under the stimulated C-peptide curve (AUC) over the first 2 hours of a mixed meal glucose tolerance test. The AUC is computed using the trapezoidal rule that is a weighted sum of the C-peptide values over the 120 minutes.
Time Frame
43 months
Title
HbA1c value
Description
The mean HbA1c over all follow-up values will be compared between the control and placebo group using a normal errors longitudinal analysis.
Time Frame
43 months
Title
Insulin Use
Description
The mean insulin dose (units/kg) over all follow-up values will be compared between the control and placebo group using a normal errors longitudinal analysis.
Time Frame
43 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Be between the ages of 18 and 45 years of age who meet the ADA standard T1DM criteria and are positive for at least 1 islet cell autoantibody. Type 1-diabetes mellitus diagnosed within the previous 2 years Must have stimulated C-peptide levels ≥ 0.2 pmol/ml measured during a mixed meal tolerance test (MMTT) conducted at least 21 days from diagnosis of diabetes and within one month (37 days) of randomization At least one month from last immunization Must be willing to comply with intensive diabetes management If participant is female with reproductive potential, she must have a negative pregnancy test and be willing to avoid pregnancy during the treatment period until 2 months after the last study drug administration. Willing to forgo routine clinical immunizations during the first 100 days after initial study drug administration (COVID-19 vaccination is permitted 60 days following initial study drug administration) Subjects must have HbA1c levels under 9.5 to be enrolled in the study. At least 30 days from receiving a single dose COVID-19 vaccine or at least 30 days from completing a multi-dose COVID-19 vaccine series. Exclusion Criteria: Be currently pregnant or lactating, or anticipate getting pregnant during the treatment period until 2 months after the last study drug administration. Ongoing use of medications known to influence glucose tolerance Require use of systemic immunosuppressant(s) Any significant diabetes complications such as renal disease (proteinuria or elevated Cr) and diabetic retinopathy Have a history of malignancies Be currently using non-insulin pharmaceuticals to affect glycemic control Have any acute or chronic complicating medical issues or abnormal clinical laboratory results that interfere with study conduct or cause increased risk including neurological abnormalities. Inability or unwillingness to comply with the provisions of this protocol Have an active infection or positive tuberculosis test result. Have serologic evidence of current or past HIV, Hep B, or Hep C infection. Have a known history of hypersensitivity or allergy reactions to squalane or squalene based adjuvants or other components of the study immunogen Subjects with a history or evidence of chronic kidney disease (serum creatinine> 1.5mg/dL) Subjects with a history of proliferative diabetic retinopathy that has not been treated with laser therapy Subjects with a history of neuropathy, foot ulcers, amputations, or kidney disease Males of reproductive potential who are unwilling to use acceptable birth control during the treatment period through 2 months after the last study drug administration, unless the female partner is postmenopausal or surgically sterile. Have current, confirmed COVID-19 infection
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Morgan Sooy
Phone
303-724-5686
Email
morgan.sooy@CUANSCHUTZ.EDU
First Name & Middle Initial & Last Name or Official Title & Degree
Hali Broncucia
Phone
303-724-7526
Email
hali.broncucia@CUANSCHUTZ.EDU
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Peter Gottlieb
Organizational Affiliation
University of Colorado, Denver
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Colorado, Denver
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Morgan Sooy
Phone
303-724-5686
Email
morgan.sooy@CUANSCHUTZ.EDU
First Name & Middle Initial & Last Name & Degree
Hali Broncucia
Phone
303-724-7526
Email
hali.broncucia@CUANSCHUTZ.EDU
First Name & Middle Initial & Last Name & Degree
Peter Gottlieb, MD

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

MER3101: MAS-1 Adjuvanted Antigen-specific Immunotherapeutic for Prevention and Treatment of Type 1 Diabetes

We'll reach out to this number within 24 hrs