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

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ClinicalTrials.gov Identifier: NCT03624062
Recruitment Status : Recruiting
First Posted : August 9, 2018
Last Update Posted : December 27, 2018
Sponsor:
Collaborators:
The Leona M. and Harry B. Helmsley Charitable Trust
Nova Immunotherapeutics Limited
Information provided by (Responsible Party):
University of Colorado, Denver

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.

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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
Estimated Study Start Date : January 2019
Estimated Primary Completion Date : April 4, 2022
Estimated Study Completion Date : April 4, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Diabetes Type 1

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.




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.



Information from the National Library of Medicine

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

Inclusion Criteria:

  • 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.
  • 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.
  • Willing to comply with intensive diabetes management.
  • If participant is female with reproductive potential, she must be willing to avoid pregnancy for 18 months and have a negative pregnancy test.
  • Willing to forgo routine clinical immunizations during the first 100 days after initial study drug administration.
  • HbA1c levels between 6.0 and 9.5 to be enrolled in the study.

Exclusion Criteria:

  • Currently pregnant or lactating or anticipate getting pregnant for 18 months after first injection.
  • 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.
  • History of malignancies.
  • Currently using non-insulin pharmaceuticals to affect glycemic control.
  • 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.
  • Active infection or positive tuberculosis test result.
  • Serologic evidence of current or past HIV, Hep B, or Hep C infection.
  • Known history of hypersensitivity or allergy reactions to squalane or squalene based adjuvants or other components of the study immunogen.
  • History or evidence of chronic kidney disease (serum creatinine > 1.5mg/dL).
  • History of proliferative diabetic retinopathy that has not been treated with laser therapy.
  • History of neuropathy, foot ulcers, amputations, or kidney disease.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03624062


Contacts
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Contact: Mara Kinney 303-724-8272 mara.kinney@ucdenver.edu
Contact: Hali Broncucia 303-724-7526 hali.broncucia!@ucdenver.edu

Locations
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United States, Colorado
University of Colorado, Denver Recruiting
Aurora, Colorado, United States, 80045
Contact: Mara Kinney    303-724-8272    mara.kinney@ucdenver.edu   
Contact: Hali Broncucia    303-724-7526    hali.broncucia@ucdenver.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
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Principal Investigator: Peter Gottlieb University of Colorado, Denver

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Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT03624062     History of Changes
Other Study ID Numbers: 15-1352
First Posted: August 9, 2018    Key Record Dates
Last Update Posted: December 27, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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