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

NCT ID: NCT04729296

Last Updated: 2021-12-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Clinical Phase

PHASE2

Study Classification

INTERVENTIONAL

Study Start Date

2021-07-01

Study Completion Date

2027-07-01

Brief Summary

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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.

Detailed Description

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Conditions

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Diabetes Mellitus, Type 1

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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).
Primary Study Purpose

PREVENTION

Blinding Strategy

DOUBLE

Participants Investigators
Active drug and placebo will be identical in appearance and packaging

Study Groups

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Golimumab

Golimumab for subcutaneous use

Group Type EXPERIMENTAL

Golimumab

Intervention Type 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

Placebo

Placebo syringes and vials matching active drug

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Inactive Drug

Interventions

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Golimumab

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

Intervention Type DRUG

Placebo

Inactive Drug

Intervention Type DRUG

Other Intervention Names

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Simponi

Eligibility Criteria

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Inclusion Criteria

1. Age \> 3 and \< 46 years
2. Willing to provide Informed Consent or have a parent or legal guardian provide informed consent if the subject is \<18 years of age
3. 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).
4. 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
5. Females of childbearing potential must agree to use abstinence or an effective birth control through the treatment period.(
6. Males able to father children, must agree to use abstinence or an effective birth control during the treatment period.
7. 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
8. Be at least 4 weeks from last live immunization
9. Be willing to forgo live vaccines through and 3 months after study drug treatment period
10. 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.
11. 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.
12. 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.

Exclusion Criteria

* 1\. 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).

2\. Have active signs or symptoms of acute infection at the time of randomization including Sars-Cov2.

3\. Have evidence of prior or current tuberculosis infection as assessed interferon gamma release assay (QuantiFERON).

4\. Be currently pregnant or lactating, or anticipate getting pregnant within the study period

5\. Require chronic use of other immunosuppressive agents including use of inhaled, intranasal, or systemic steroids

6\. Have evidence of current or past HIV, Hepatitis B, histoplasmosis, coccidioidomycosis, or current Hepatitis C infection.

7\. Have any complicating medical issues or abnormal clinical laboratory results that may interfere with study conduct, or cause increased risk to include pre-existing pulmonary, GI, renal, cardio-vascular disease, neurological disease (i.e. demyelinating disease), psychiatric disease or blood count abnormalities. Note pre-existing treated celiac or thyroid disease are not exclusionary diagnoses.

8\. Have a history of malignancies other than of skin

9\. Evidence of liver dysfunction with aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than 2 times the upper limits of normal

10\. Evidence of renal dysfunction with creatinine greater than 1.5 times the upper limit of normal for age and sex.

11\. Known history of congestive heart failure or left ventricular dysfunction.

12\. Vaccination with a live virus within the last 4 weeks

13\. Current or ongoing use of non-insulin pharmaceuticals that affect glycemic control within 30 days of screening (see section 4.5 for list of exclusionary pharmaceuticals).

14\. Active participation in another intervention study in the previous 30 days

15\. Known allergy to Anti-TNFα or latex.

16\. Any condition that in the investigator's opinion may adversely affect study participation or may compromise the study results

17\. Previously diagnosed with T1D according to American Diabetes Association (ADA) criteria
Minimum Eligible Age

3 Years

Maximum Eligible Age

46 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of South Florida

OTHER

Sponsor Role collaborator

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Carla Greenbaum, MD

Role: STUDY_CHAIR

Type 1 Diabetes TrialNet

Related Links

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http://www.trialnet.org/

TrialNet Public Website

Other Identifiers

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2U01DK106993-02

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1UC4DK117009-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

TN30 Anti-TNFα

Identifier Type: -

Identifier Source: org_study_id