MAS-1 Adjuvanted Immunotherapy for Type 1 Diabetes

(MER3101 Trial)

Recruiting in Palo Alto (17 mi)

Overseen by Peter Gottlieb, MD

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: University of Colorado, Denver

Must not be taking: Immunosuppressants, Non-insulin glycemic

Disqualifiers: Pregnancy, Renal disease, Malignancies, others

Stay on Your Current Meds

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial tests a new vaccine mixed with a booster substance to help patients with type 1 diabetes. The goal is to retrain their immune system to stop attacking insulin-producing cells, potentially improving their condition.

Do I need to stop my current medications for the trial?

The trial requires that you do not use medications that influence glucose tolerance or systemic immunosuppressants. If you are using non-insulin drugs to control blood sugar, you will need to stop those as well.

What data supports the effectiveness of the MAS-1 adjuvanted immunotherapy treatment for type 1 diabetes?

Research shows that MAS-1 adjuvanted immunotherapy can generate strong immune responses that help prevent diabetes in mice, with a significant number remaining diabetes-free for up to a year. Additionally, insulin B-chain immunotherapy has been effective in reducing diabetes incidence in animal models, suggesting potential benefits for type 1 diabetes. ^{1 2 3 4 5}

Is MAS-1 adjuvanted immunotherapy safe for humans?

The MAS-1 adjuvanted immunotherapy has been evaluated in a phase I clinical trial for type 1 diabetes and was found to be generally safe and well-tolerated in humans. ^{1 2 3 4 6}

How is the MAS-1 adjuvanted Insulin B-chain treatment different from other treatments for type 1 diabetes?

The MAS-1 adjuvanted Insulin B-chain treatment is unique because it uses a nanoparticular, emulsion-based adjuvant (a substance that enhances the body's immune response to an antigen) to promote Th2 and regulatory immune responses, which can provide long-term protection against type 1 diabetes. This approach focuses on modulating the immune system rather than directly affecting blood sugar levels, which is different from standard insulin therapies. ^{1 2 3 4 7}

Research Team

Peter Gottlieb, MD

Principal Investigator

University of Colorado, Denver

Eligibility Criteria

This trial is for adults aged 18-45 with Type 1 Diabetes diagnosed in the last 2 years, positive for an islet cell autoantibody, and have certain levels of C-peptide. Participants must not be pregnant or planning pregnancy soon, avoid other vaccines initially, and manage diabetes intensively. Exclusions include those with significant complications or infections, drug sensitivities, or unwilling to use birth control.

Inclusion Criteria

I agree not to get routine vaccines for the first 100 days after starting the study drug, except for the COVID-19 vaccine after 60 days.

I am not pregnant and agree to prevent pregnancy during and up to 2 months after treatment.

It has been over a month since my last vaccination.

Exclusion Criteria

I have had cancer before.

I have serious diabetes complications like kidney issues or eye problems.

I am taking medication that affects my blood sugar levels.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive two intramuscular doses at days 0 and 28 of either MAS-1 placebo emulsion or MAS-1 adjuvanted IBC at varying doses

4 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including immunologic analysis and monitoring of adverse events

43 months

Treatment Details

Interventions

• MAS-1 adjuvanted Insulin B-chain (Immunotherapy)

Trial Overview The study tests MAS-1 adjuvanted Insulin B-chain's safety and its ability to promote immune tolerance in Type 1 Diabetes. It's a randomized (participants are chosen by chance), double-masked (neither researchers nor participants know who gets the real treatment), placebo-controlled trial that gradually increases doses.

Participant Groups

Group I: TBD ug IBC in 0.25 mL MAS-1 emulsion Experimental Treatment 1 Intervention

7 participants to be randomized between placebo and MAS-1 adjuvanted insulin B-chain (2:5) with the optimal IBC dose selected from the first 3 groups (either 33 µg, or 109 µg, or 327 µg IBC) in 0.25 mL MAS-1 emulsion

Group II: 33 ug IBC in 0.25 mL MAS-1 emulsion Experimental Treatment 1 Intervention

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

Group III: 327 ug IBC in 0.25 mL MAS-1 emulsion Experimental Treatment 1 Intervention

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

Group IV: 109 ug IBC in 0.25 mL MAS-1 emulsion Experimental Treatment 1 Intervention

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

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

Aviva Abosch

University of Colorado, Denver

Chief Medical Officer since 2019

MD

Uday B. Kompella

University of Colorado, Denver

Chief Executive Officer since 2015

PhD in Pharmaceutical Sciences

The Leona M. and Harry B. Helmsley Charitable Trust

Collaborator

Trials

69

Recruited

101,000+

Sarah E. Paul

The Leona M. and Harry B. Helmsley Charitable Trust

Chief Executive Officer since 2021

Harvard summa cum laude, J.D. from Harvard Law School

Walter Panzirer

The Leona M. and Harry B. Helmsley Charitable Trust

Chief Medical Officer since 2021

MD

Nova Immunotherapeutics Limited

Industry Sponsor

Trials

2

Recruited

130+

Findings from Research

The MAS-1 adjuvant, when used with insulin-based immunotherapies, showed significant long-term protection against type 1 diabetes in NOD mice, with 60% to 73% remaining diabetes-free at 35 and 52 weeks.

MAS-1 alone also provided protective effects, promoting regulatory immune responses characterized by increased levels of IL-10 and Th2 cytokines, suggesting its potential for use in early-stage type 1 diabetes prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MAS-1 adjuvant immunotherapy generates robust Th2 type and regulatory immune responses providing long-term protection from diabetes in late-stage pre-diabetic NOD mice. Zhang, L., Londono, P., Yu, L., et al.[2021]

Immunization with the insulin B chain, combined with an adjuvant, significantly reduced the incidence of diabetes in diabetes-prone BB/W rats, indicating a potential preventive strategy against insulin-dependent diabetes mellitus (IDDM).

The study found that the frequency of immunization mattered, with weekly injections leading to a notably lower rate of diabetes, suggesting that the timing and method of immunization can enhance its effectiveness in modulating the autoimmune response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human insulin B chain but not A chain decreases the rate of diabetes in BB rats. Song, HY., Abad, MM., Mahoney, CP., et al.[2019]

Immunization with islet-specific autoantigens, particularly insulin B chain and GAD65, significantly delayed the onset of insulin-dependent diabetes in NOD mice, indicating a promising approach for preventing the disease.

The study found that insulin B chain not only delayed diabetes onset but also reduced the incidence of cyclophosphamide-accelerated diabetes by about 50-55%, suggesting its potential for enhancing protection against autoimmune diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunization therapies in the prevention of diabetes. Ramiya, VK., Lan, MS., Wasserfall, CH., et al.[2011]

A phase I clinical trial involving 12 subjects with recently diagnosed type 1 diabetes showed that a single injection of a novel antigen-specific therapy was generally safe and well-tolerated over a 2-year follow-up period.

The therapy successfully induced robust insulin-specific immune responses, including the generation of regulatory T cells, suggesting potential for further development in treating type 1 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autoantigen-specific regulatory T cells induced in patients with type 1 diabetes mellitus by insulin B-chain immunotherapy. Orban, T., Farkas, K., Jalahej, H., et al.[2021]

Intermittent immunizations with insulin's B-chain in nonobese diabetic (NOD) mice effectively prevent diabetes, suggesting a potential therapeutic approach for autoimmune diabetes.

The mechanism involves inducing a protective immune response that alters the nature of insulitis lesions, reducing harmful inflammation and promoting a more protective state, although it does not decrease the overall inflammation present.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Insulin immunization of nonobese diabetic mice induces a protective insulitis characterized by diminished intraislet interferon-gamma transcription. Muir, A., Peck, A., Clare-Salzler, M., et al.[2018]

In a study involving female NOD mice, the combination of insulin peptide B:9-23 with a nondepleting anti-CD4 monoclonal antibody (YTS 177.9) resulted in 70% of the combination-treated mice remaining diabetes-free after one year, indicating a significant protective effect against diabetes.

The anti-CD4 antibody not only suppressed insulin autoantibodies but also enhanced the efficacy of the B:9-23 peptide, suggesting that this combination therapy could be a promising approach for long-term diabetes prevention in type 1 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nondepleting anti-CD4 monoclonal antibody prevents diabetes and blocks induction of insulin autoantibodies following insulin peptide B:9-23 immunization in the NOD mouse. Liu, E., Moriyama, H., Paronen, J., et al.[2019]

Immunization with the insulin B chain peptide (p9-23) effectively delayed the onset of insulin-dependent diabetes mellitus (IDDM) in a study using alum as an adjuvant, showing a significant protective effect (P = 0.012).

The Diphtheria-Tetanus toxoid-Acellular Pertussis (DTP) vaccine also provided significant protection against diabetes (P < 0.003) and enhanced the anti-diabetic effect when combined with insulin B chain, suggesting a promising strategy for clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antigen based therapies to prevent diabetes in NOD mice. Ramiya, VK., Shang, XZ., Pharis, PG., et al.[2007]

References

1. England pubmed.ncbi.nlm.nih.gov

MAS-1 adjuvant immunotherapy generates robust Th2 type and regulatory immune responses providing long-term protection from diabetes in late-stage pre-diabetic NOD mice. [2021]

2. Ireland pubmed.ncbi.nlm.nih.gov

Human insulin B chain but not A chain decreases the rate of diabetes in BB rats. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Immunization therapies in the prevention of diabetes. [2011]

4. England pubmed.ncbi.nlm.nih.gov

Autoantigen-specific regulatory T cells induced in patients with type 1 diabetes mellitus by insulin B-chain immunotherapy. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Insulin immunization of nonobese diabetic mice induces a protective insulitis characterized by diminished intraislet interferon-gamma transcription. [2018]

6. England pubmed.ncbi.nlm.nih.gov

Nondepleting anti-CD4 monoclonal antibody prevents diabetes and blocks induction of insulin autoantibodies following insulin peptide B:9-23 immunization in the NOD mouse. [2019]

7. England pubmed.ncbi.nlm.nih.gov

Antigen based therapies to prevent diabetes in NOD mice. [2007]