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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

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:

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

Sites / Locations

University of Colorado, DenverRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

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

NCT ID

NCT03624062

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

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

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

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

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

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

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

morgan.sooy@CUANSCHUTZ.EDU

First Name & Middle Initial & Last Name or Official Title & Degree

Hali Broncucia

Phone

303-724-7526

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

morgan.sooy@CUANSCHUTZ.EDU

First Name & Middle Initial & Last Name & Degree

Hali Broncucia

Phone

303-724-7526

hali.broncucia@CUANSCHUTZ.EDU

First Name & Middle Initial & Last Name & Degree

Peter Gottlieb, MD

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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