Anti-TNFα to Delay or Prevent Progression to Stage 3 T1D

NCT04729296 | Withdrawn Phase 2 DMC FDA Drug

• 3 other identifiers: TN30 Anti-TNFα2U01DK106993-021UC4DK117009-01
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This will be a study conducted as a placebo-controlled, double blind, 1:1 randomized controlled clinical trial testing a Tumor Necrosis Factor Blocker (Anti-TNFα) substance versus placebo in subjects with a 2-year 50% risk of progression to stage 3 T1D across multiple centers. The trial will investigate the ability of Anti-TNFα to prevent or delay progression to Stage 3 T1D in the targeted patient population.

Conditions

Diabetes Mellitus, Type 1

Outcome Measures

Primary Outcomes (1)

• The primary outcome is the elapsed time from random treatment assignment to the development of diabetes (T1D) or time of last contact among those randomized

  The primary outcome is the elapsed time from random treatment assignment to the development of diabetes (T1D) or time of last contact among those randomized

  6 years

Study Arms (2)

Golimumab

EXPERIMENTAL

Golimumab for subcutaneous use

Drug: Golimumab

Placebo

PLACEBO COMPARATOR

Placebo syringes and vials matching active drug

Drug: Placebo

Interventions

Golimumab DRUG

For participants ≥45 kg, 50 mg of golimumab will be administered subcutaneously For participants \<45 kg, the dose of golimumab is 30 mg/m2 to maximum of 50 mg

Also known as: Simponi

Golimumab

Placebo DRUG

Inactive Drug

Placebo

Eligibility Criteria

• Age: 3 Years - 46 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age \> 3 and \< 46 years
• Willing to provide Informed Consent or have a parent or legal guardian provide informed consent if the subject is \<18 years of age
• At least two or more diabetes-related biochemical autoantibodies insulin (mIAA), glutamic acid decarboxylase antibody (GADA), Islet cytoplasmic antibodies (ICA), islet antigen 2 (IA-2A), zinc transporter 8 (ZnT8A) present on the same sample. Of note, ICA and GADA positivity alone cannot be used to define eligibility in this trial).
• Must have at least two of the high-risk markers defined below (within 7 weeks (52 days) of screening visit if performed as part of TN01 Pathway to Prevention (PTP) study at time of screening; defining a 50% two-year progression risk):
• a. Abnormal glucose tolerance: i. 2-hr glucose ≥ 140 and \<200 mg/dL, fasting glucose ≥ 110 and \<126, or 30-, 60-, or 90-minute glucose ≥ 200 mg/dL b. HbA1c ≥ 5.7 c. Index60 ≥ 1.4 d. Diabetes Prevention Trial-Type 1 Risk Score (DPTRS) ≥ 7.4
• Females of childbearing potential must agree to use abstinence or an effective birth control through the treatment period.(
• Males able to father children, must agree to use abstinence or an effective birth control during the treatment period.
• Subjects who are Epstein-Barr virus (EBV) seronegative at screening must be EBV Polymerase chain reaction (PCR) negative within 30 days of randomization and may not have had signs or symptoms of an EBV compatible illness lasting longer than 7 days within 30 days of randomization
• Be at least 4 weeks from last live immunization
• Be willing to forgo live vaccines through and 3 months after study drug treatment period
• Be up to date on all recommended vaccinations based on age of subject and willing to receive killed influenza vaccine when available for current or upcoming season.
• If prior treatment with active study agent from previous clinical trial, approval of medical monitor and investigator that such prior treatment does not impact risk for current study.
• Subjects who have met all above criteria must have the qualifying oral glucose tolerance test (OGTT) within 7 weeks (52 days) of randomization and baseline visit.

You may not qualify if:

• \. Be immunodeficient or have clinically significant chronic lymphopenia: (Leukopenia (\< 3,000 leukocytes /μL), neutropenia (\<1,500 neutrophils/μL), lymphopenia (\<800 lymphocytes/μL), or thrombocytopenia (\<100,000 platelets/μL).
• \. Have active signs or symptoms of acute infection at the time of randomization including Sars-Cov2.
• \. Have evidence of prior or current tuberculosis infection as assessed interferon gamma release assay (QuantiFERON).
• \. Be currently pregnant or lactating, or anticipate getting pregnant within the study period
• \. Require chronic use of other immunosuppressive agents including use of inhaled, intranasal, or systemic steroids
• \. Have evidence of current or past HIV, Hepatitis B, histoplasmosis, coccidioidomycosis, or current Hepatitis C infection.
• \. Have a history of malignancies other than of skin
• \. Evidence of liver dysfunction with aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than 2 times the upper limits of normal
• \. Evidence of renal dysfunction with creatinine greater than 1.5 times the upper limit of normal for age and sex.
• \. Known history of congestive heart failure or left ventricular dysfunction.
• \. Vaccination with a live virus within the last 4 weeks
• \. Active participation in another intervention study in the previous 30 days
• \. Known allergy to Anti-TNFα or latex.
• \. Any condition that in the investigator's opinion may adversely affect study participation or may compromise the study results
• \. Previously diagnosed with T1D according to American Diabetes Association (ADA) criteria

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): lead
• University of South Florida: collaborator

Related Links

• TrialNet Public Website

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

golimumab

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Carla Greenbaum, MD

  Type 1 Diabetes TrialNet

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Active drug and placebo will be identical in appearance and packaging
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Model Details: Treatment assignment (active drug: placebo) will be assigned in a parallel, randomized, 1:1 model. Randomization will be conducted using block randomization with variable block sizes with stratification on TrialNet study site and age group (\< 12 years old vs. 12 years old or older).

Study Record Dates

• First Submitted: January 20, 2021
• First Posted: January 28, 2021
• Study Start: July 1, 2021
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027
• Last Updated: December 2, 2021

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will share