Multiple Ascending Dose (MAD) Study of IMT-002 in HLA-DQ8-positive Type 1 Diabetes

NCT04625595 | Completed Phase 1 FDA Drug

• 1 other identifier: IMT-002-0102
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 3

Brief Summary

This study is designed to characterize the safety, steady-state pharmacokinetics (PK) of IMT-002, and will serve as a dose range identification for the pharmacodynamic effect of blocking self-antigen presentation in adults with type 1 diabetes (T1D) having the human leukocyte antigen (HLA)-DQ8 gene.

Conditions

Type1 Diabetes

Keywords

diabetes; prescreening; autoimmunity; HLA

Outcome Measures

Primary Outcomes (3)

• Incidence of adverse events (AEs) and serious adverse events (SAEs)

  Frequency tabulated as number of participants with adverse and serious adverse events (AEs)

  Treatment and follow-up period, Day 21

• Change from baseline in electrocardiogram (ECG)

  Single 12-lead ECG will be measured in a supine position after 5 minutes rest and measure QRS, QT, and QTc intervals

  Day 1, Day 7, Day 14 and Day 21

• Change in total daily insulin use

  At each study visit, total daily insulin (ie, total insulin administered over the previous 24-hour period) will be entered in the Concomitant Medications CRF

  Day 1, Day 7, Day 14 and Day 21

Secondary Outcomes (2)

• Pharmacokinetic (PK) measurement in blood plasma, Cmax

  Day 1, Day 7, Day 14

• Cytokine level from in vitro presentation of antigen by HLA-DQ8

  Day 1, Day 7, Day 14 and Day 21

Study Arms (4)

350 mg BID (700 mg total daily dose) of active drug or placebo

EXPERIMENTAL

Low dose, drug IMT-002

Drug: 350mg BID (700mg total daily) IMT-002, D-methyldopa, active formulation in capsule or Placebo, microcrystalline cellulose in capsule

1050 mg QD (1050 mg total daily dose) of active drug or placebo

EXPERIMENTAL

Moderate dose, drug IMT-002

Drug: 1050mg QD (1050mg total daily) IMT-002, D-methyldopa, active formulation in capsule or Placebo, microcrystalline cellulose in capsule

700 mg BID (1400 mg total daily dose) of active drug or placebo

EXPERIMENTAL

Moderate to high dose, drug IMT-002

Drug: 700mg BID (1400mg total daily) IMT-002, D-methyldopa, active formulation in capsule or Placebo, microcrystalline cellulose in capsule

1050 mg BID (2100 mg total daily dose) of active drug or placebo

EXPERIMENTAL

High dose, drug IMT-002

Drug: 1050mg BID (2100mg total daily) IMT-002, D-methyldopa, active formulation in capsule or Placebo, microcrystalline cellulose in capsule

Interventions

350mg BID (700mg total daily) IMT-002, D-methyldopa, active formulation in capsule or Placebo, microcrystalline cellulose in capsule DRUG

Oral drug or placebo self-administered by subject as a capsule by mouth once-daily or twice-daily

Also known as: 350mg BID

350 mg BID (700 mg total daily dose) of active drug or placebo

700mg BID (1400mg total daily) IMT-002, D-methyldopa, active formulation in capsule or Placebo, microcrystalline cellulose in capsule DRUG

Oral drug or placebo self-administered by subject as a capsule by mouth once-daily or twice-daily

Also known as: 700mg BID

700 mg BID (1400 mg total daily dose) of active drug or placebo

1050mg QD (1050mg total daily) IMT-002, D-methyldopa, active formulation in capsule or Placebo, microcrystalline cellulose in capsule DRUG

Oral drug or placebo self-administered by subject as a capsule by mouth once-daily or twice-daily

Also known as: 1050mg QD

1050 mg QD (1050 mg total daily dose) of active drug or placebo

1050mg BID (2100mg total daily) IMT-002, D-methyldopa, active formulation in capsule or Placebo, microcrystalline cellulose in capsule DRUG

Oral drug or placebo self-administered by subject as a capsule by mouth once-daily or twice-daily

Also known as: 1050mg BID

1050 mg BID (2100 mg total daily dose) of active drug or placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Signed the ICF as described in Appendix 3 which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
• Man or woman, 18 to 45 years of age inclusive at the time of signing the ICF.
• Has received a diagnosis of T1D according to the criteria from the American Diabetes Association.
• Positive for at least one gene encoding for HLA-DQ8 (DQB\*0302).
• If male, and of reproductive potential, willing to use medically acceptable birth control (Appendix 5), unless the female partner is postmenopausal or surgically sterile, until study completion and for at least 30 days after the last dose of study treatment and refrain from donating sperm during this period.
• If female: (a) surgically sterile or (b) postmenopausal or (c) if of reproductive potential, willing to use medically acceptable birth control (eg, female hormonal contraception, barrier methods or sterilization (Appendix 5) until study completion and for at least 30 days (one menstrual cycle).

You may not qualify if:

• Inability or unwillingness of a subject to give written informed consent or comply with the study protocol.
• No HLA-DQ8 gene (DQB\*03:02).
• Any of the following hematologic abnormalities at the time of screening, confirmed by repeat tests:
• Leukopenia (\<3,000 leukocytes/μL)
• Neutropenia (\<1,500 neutrophils/μL)
• Thrombocytopenia (\<125,000 platelets/μL)
• Hemoglobin less than 10 g/dl
• Evidence of liver dysfunction, with ALT \> 2.5 times the upper limit of normal (ULN) or AST \>3.0 times ULN persistent for 1 week or greater.
• Evidence of renal insufficiency as indicated by serum creatinine of \>1.5 times ULN, confirmed by a repeat test.
• Clinically significant abnormal physical examination, vital signs, or 12-lead ECG at screening as deemed appropriate by the investigator.
• Has a history of or current clinically significant medical illness including, but not limited to, cardiac arrhythmias or other cardiac disease; significant pulmonary disease; neurologic or psychiatric disease; infection; or any other illness that the investigator considers should exclude the subject or that could interfere with the interpretation of the study results.
• Body mass index (BMI) \> 32 kg/m2.
• Unstable blood sugar control defined as one or more episodes of severe hypoglycemia (defined as hypoglycemia that required the assistance of another person) within the last 30 days.
• Use of a treatment that is known to cause a significant, ongoing change in the course of T1D or immunologic status, within 4 weeks prior to participation; this includes high-dose inhaled, extensive topical or systemic glucocorticoids.
• History of any organ transplant, including islet cell transplant.

Sponsors & Collaborators

• Immunomolecular Therapeutics, Inc.: lead
• WCCT Global: collaborator

Study Sites (3)

Prosciento, Inc.

Chula Vista, California, 91911, United States

Location

Barbara Davis Center

Aurora, Colorado, 80045, United States

Location

Rainier Clinical Research Center

Renton, Washington, 98057, United States

Location

Related Publications (5)

• Ostrov DA, Alkanani A, McDaniel KA, Case S, Baschal EE, Pyle L, Ellis S, Pollinger B, Seidl KJ, Shah VN, Garg SK, Atkinson MA, Gottlieb PA, Michels AW. Methyldopa blocks MHC class II binding to disease-specific antigens in autoimmune diabetes. J Clin Invest. 2018 May 1;128(5):1888-1902. doi: 10.1172/JCI97739. Epub 2018 Apr 3.

  PMID: 29438107 BACKGROUND

• Ostrov DA, Gottlieb PA, Michels AW. Rationally designed small molecules to prevent type 1 diabetes. Curr Opin Endocrinol Diabetes Obes. 2019 Apr;26(2):90-95. doi: 10.1097/MED.0000000000000470.

  PMID: 30694829 BACKGROUND

• Au WY, Dring LG, Grahame-Smith DG, Isaac P, Williams RT. The metabolism of 14 C-labelled -methyldopa in normal and hypertensive human subjects. Biochem J. 1972 Aug;129(1):1-10. doi: 10.1042/bj1290001.

  PMID: 4646774 BACKGROUND

• GILLESPIE L Jr, OATES JA, CROUT JR, SJOERDSMA A. Clinical and chemical studies with alpha-methyl-dopa in patients with hypertension. Circulation. 1962 Feb;25:281-91. doi: 10.1161/01.cir.25.2.281. No abstract available.

  PMID: 13898638 BACKGROUND

• SJOERDSMA A, VENDSALU A, ENGELMAN K. STUDIES ON THE METABOLISM AND MECHANISM OF ACTION OF METHYLDOPA. Circulation. 1963 Oct;28:492-502. doi: 10.1161/01.cir.28.4.492. No abstract available.

  PMID: 14068757 BACKGROUND

MeSH Terms

Conditions

Diabetes Mellitus; Autoimmune Diseases

Interventions

BID protein, human; Capsules; microcrystalline cellulose

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 20, 2020
• First Posted: November 12, 2020
• Study Start: November 9, 2020
• Primary Completion: May 11, 2021
• Study Completion: July 31, 2021
• Last Updated: August 25, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)