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

• ClinicalTrials.gov Identifier: NCT03624062
• Recruitment Status: Recruiting
• First Posted: August 9, 2018
• Last Update Posted: May 6, 2022
• Sponsor: University of Colorado, Denver
• Collaborators: The Leona M. and Harry B. Helmsley Charitable Trust; Nova Immunotherapeutics Limited
• Information provided by (Responsible Party): University of Colorado, Denver

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.

Condition or disease	Intervention/treatment	Phase
Type 1 Diabetes Mellitus	Drug: MAS-1 adjuvanted Insulin B-chain	Phase 1

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 28 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: MER3101: MAS-1 Adjuvanted Antigen-specific Immunotherapeutic for Prevention and Treatment of Type 1 Diabetes
• Actual Study Start Date: August 31, 2020
• Estimated Primary Completion Date: April 4, 2023
• Estimated Study Completion Date: April 4, 2023

Arms and Interventions

Arm	Intervention/treatment
33 ug IBC 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 33 ug IBC dose in 0.25 mL MAS-1 emulsion	Drug: MAS-1 adjuvanted Insulin B-chain; 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.
109 ug IBC 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	Drug: MAS-1 adjuvanted Insulin B-chain; 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.
327 ug IBC 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	Drug: MAS-1 adjuvanted Insulin B-chain; 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.
TBD ug IBC in 0.5 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	Drug: MAS-1 adjuvanted Insulin B-chain; 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.

Outcome Measures

Primary Outcome Measures :

1. Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [ Time Frame: 43 months ]
   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.
2. Immunologic Analysis [ Time Frame: 43 months ]
   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 :

1. Mean C-peptide AUC value [ Time Frame: 43 months ]
   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.
2. HbA1c value [ Time Frame: 43 months ]
   The mean HbA1c over all follow-up values will be compared between the control and placebo group using a normal errors longitudinal analysis.
3. Insulin Use [ Time Frame: 43 months ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 45 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Contacts

Contact: Morgan Sooy; 303-724-5686; morgan.sooy@CUANSCHUTZ.EDU

Contact: Hali Broncucia; 303-724-7526; hali.broncucia@CUANSCHUTZ.EDU

Locations

United States, Colorado

University of Colorado, Denver; Recruiting

Aurora, Colorado, United States, 80045

Contact: Morgan Sooy 303-724-5686 morgan.sooy@CUANSCHUTZ.EDU

Contact: Hali Broncucia 303-724-7526 hali.broncucia@CUANSCHUTZ.EDU

Principal Investigator: Peter Gottlieb, MD

Sponsors and Collaborators

University of Colorado, Denver

The Leona M. and Harry B. Helmsley Charitable Trust

Nova Immunotherapeutics Limited

Investigators

• Principal Investigator: Peter Gottlieb; University of Colorado, Denver

More Information

• Responsible Party: University of Colorado, Denver
• ClinicalTrials.gov Identifier: NCT03624062
• Other Study ID Numbers: 15-1352
• First Posted: August 9, 2018
• Last Update Posted: May 6, 2022
• Last Verified: May 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University of Colorado, Denver:

New onset

Additional relevant MeSH terms:

Diabetes Mellitus; Diabetes Mellitus, Type 1; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Insulin; Hypoglycemic Agents; Physiological Effects of Drugs