MAS-1 Adjuvanted Immunotherapy for Type 1 Diabetes

(MER3101 Trial)

Overseen By Morgan Sooy

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Colorado, Denver

Must not be taking: Immunosuppressants, Non-insulin glycemic

Disqualifiers: Pregnancy, Renal disease, Malignancies, others

Stay on Your Current Meds You can continue your current medications while participating

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

Duration: 4 weeks

28 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment option for people with type 1 diabetes (T1D). The researchers aim to determine if adding MAS-1 to insulin B-chain (an adjuvanted immunotherapy) can safely restore the immune system and help reverse T1D autoimmunity. Participants will be divided into groups to receive different doses of the treatment or a placebo. Those diagnosed with T1D within the past two years and possessing at least one islet cell autoantibody may be suitable for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

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.

Is there any evidence suggesting that MAS-1 adjuvanted Insulin B-chain is likely to be safe for humans?

Research has shown that MAS-1 adjuvanted insulin B-chain can safely boost the immune system. In mouse studies, this treatment generated strong immune responses that helped prevent type 1 diabetes, with many mice remaining diabetes-free after receiving it.

As a Phase 1 trial, the primary goal is to assess the treatment's safety and tolerability in humans. Phase 1 trials mark the first time a treatment is tested in people, so information about side effects in humans may be limited. However, the positive results in animal studies suggest it could be safe. Participants in this trial will help determine if these results are similar in humans. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Unlike the standard treatments for Type 1 Diabetes, which typically involve regular insulin injections, the MAS-1 adjuvanted insulin B-chain therapy introduces a novel approach by combining insulin with an adjuvant to potentially enhance the immune response. This treatment is unique because it aims to modulate the immune system, possibly offering a more targeted way to address the autoimmune aspect of Type 1 Diabetes. Researchers are particularly excited about the possibility that this therapy could slow down or even halt the progression of the disease, offering a transformative benefit beyond just managing blood sugar levels.

What evidence suggests that MAS-1 adjuvanted Insulin B-chain might be an effective treatment for type 1 diabetes?

Research has shown that MAS-1 adjuvanted insulin B-chain (IBC) might help prevent type 1 diabetes by calming the immune system. In studies with mice, this treatment kept many diabetes-free for an extended period—up to 73% remained healthy after 35 weeks. MAS-1 encourages the body to create specific immune responses that may control the harmful effects seen in type 1 diabetes. Although most current data comes from animal studies, these results are promising for future human treatments. In this trial, participants will receive randomized doses of MAS-1 adjuvanted insulin B-chain to evaluate its effectiveness and safety in humans. ^{1 2 3 4 6}

Who Is on the Research Team?

Peter Gottlieb, MD

Principal Investigator

University of Colorado, Denver

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• MAS-1 adjuvanted Insulin B-chain

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.

How Is the Trial Designed?

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+

The Leona M. and Harry B. Helmsley Charitable Trust

Collaborator

Trials

69

Recruited

101,000+

Nova Immunotherapeutics Limited

Industry Sponsor

Trials

2

Recruited

130+

Published Research Related to This Trial

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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03624062

NCT03624062 | MER3101: MAS-1 Adjuvanted Antigen- ... 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 ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/24783965/

MAS-1 adjuvant immunotherapy generates robust Th2 type ... MAS-1, a nanoparticular, emulsion-based adjuvant, was evaluated for its ability to promote Th2 and regulatory immune responses and prevent type 1 diabetes ...

3. withpower.com withpower.com/trial/phase-1-diabetes-mellitus-7-2020-44954

MAS-1 Adjuvanted Immunotherapy 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 ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4515961/

MAS-1 adjuvant immunotherapy generates robust Th2 type ... MAS-1, a nanoparticular, emulsion-based adjuvant, was evaluated for its ability to promote Th2 and regulatory immune responses and prevent type 1 diabetes ...

5. researchgate.net researchgate.net/publication/262023007_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

MAS-1 adjuvant immunotherapy generates robust Th2 type ... MER3101 and MER3102 provided long-term protection with 60% and 73% of mice remaining diabetes-free at week 35, and 60% and 47% at week 52. MAS-1 ...

6. policylab.us policylab.us/clinical-trials/l/colorado/condition/type-1-diabetes?page=2

Type 1 Diabetes Paid Clinical Trials in Colorado - Policy Lab This trial plans to learn more about the effects of a medication, semaglutide, on cardiovascular function, kidney function, and insulin sensitivity in ...