Modulation of STAT3 Signaling With Siltuximab in Type 1 Diabetes

• ClinicalTrials.gov Identifier: NCT02641522
• Recruitment Status: Completed
• First Posted: December 29, 2015
• Results First Posted: October 9, 2018
• Last Update Posted: November 2, 2018
• Sponsor: Carla Greenbaum, MD
• Collaborator: Janssen Research & Development, LLC
• Information provided by (Responsible Party): Carla Greenbaum, MD, Benaroya Research Institute

Study Description

Brief Summary:

The purpose of this study is to evaluate the effects of siltuximab on immune cell functions in patients with Type 1 diabetes (T1D).

Condition or disease	Intervention/treatment	Phase
Type 1 Diabetes	Drug: Siltuximab	Early Phase 1

Detailed Description:

This is an open-label (all people know the identity of the intervention), single center, non-randomized (patients are not assigned by chance to treatment groups), Mechanistic Study (a study that focuses on the biologic activity of the drug, rather than on disease treatment). Up to 10 patients with Type 1 diabetes (T1D) will be enrolled in the study. Participants will receive a single dose of siltuximab and blood samples will be obtained a total of 6 times until 12 weeks after dosing. Cells will be isolated from the blood samples and used to measure specific activities of cells in the immune system. Safety evaluations for adverse events, clinical laboratory tests, vital signs, and physical examination will be performed throughout the study. The end of study is the date of the last assessment for the last patient.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Modulation of STAT3 Signaling With Siltuximab in Type 1 Diabetes
• Actual Study Start Date: March 8, 2016
• Actual Primary Completion Date: March 16, 2017
• Actual Study Completion Date: March 16, 2017

Arms and Interventions

Arm	Intervention/treatment
Experimental: Post-Infusion; Single infusion of siltuximab (11 mg/kg)	Drug: Siltuximab; Single infusion of siltuximab (11 mg/kg); Other Name: Sylvant

Outcome Measures

Primary Outcome Measures :

1. Percent Change From Baseline in IL-6 Stimulated Intracellular p-STAT3 at Week 12 [ Time Frame: 0-to-12 weeks ]
   Change in IL-6 stimulated intracellular p-STAT3 between Week 12 and baseline

Other Outcome Measures:

1. Adverse Event Monitoring [ Time Frame: 0-to-12 weeks ]
   Monitor adverse events associated with siltuximab treatment. All AE related to study drug will be tabulated along with their grade.

Eligibility Criteria

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

Criteria

Inclusion Criteria:

1. Positive for at least one diabetes-related autoantibody any time since diagnosis, including by not limited to: Glutamate decarboxylase (GAD-65) Insulin, if obtained within 10 days of the onset of exogenous insulin therapy; IA-2; ZnT8
2. Peak stimulated C-peptide level ≥ 0.1 pmol/mL following a mixed meal tolerance test (MMTT) conducted within 60 days of enrollment
3. Females of child-bearing potential must be willing to use effective birth control and refrain from donating eggs for the purposes of assisted reproduction for duration of study.
4. A woman of childbearing potential must have a negative serum (β-human chorionic gonadotropin [β-hCG]) or urine pregnancy test at screening and prior to dosing.
5. During the study, and for 3 months after receiving the study agent, a woman must agree to not donate eggs (ova, oocytes) for the purposes of assisted reproduction.
6. Willing and able to give informed consent for participation.

Exclusion Criteria:

1. History of severe reaction or anaphylaxis to human, humanized or murine monoclonal antibodies;
2. History of malignancy or serious uncontrolled cardiovascular disease or hypertension, nervous system, pulmonary, renal, or gastrointestinal disease, or significant dyslipidemia despite therapy;
3. Any history of recent (within 3 months) serious bacterial, viral, fungal, or other opportunistic infections;
4. History or serologic evidence of current or past HIV, Hepatitis B, or Hepatitis C;
5. Positive QuantiFERON or PPD TB test, history of tuberculosis, or active TB infection;
6. Active infection with EBV ;
7. Active infection with CMV;
8. Diagnosis of liver disease or elevated hepatic enzymes, confirmed by repeat tests, as defined by ALT, AST, or both > 1.5 x the upper limit of age-determined normal (ULN) or total bilirubin > ULN;

9. Any of the following hematologic abnormalities, confirmed by repeat tests:

   • White blood count <3,000/μL or >14,000/μL
   • Lymphocyte count <500/μL
   • Platelet count <150,000 /μL
   • Hemoglobin <8.5 g/dL or > or = to 17 g/dL
   • Neutrophil count <2,000 cells/μL
10. Females who are pregnant or lactating;
11. Receipt of live vaccine (e.g. varicella, measles, mumps, rubella, cold-attenuated intranasal influenza vaccine, bacillus Calmette-Guérin, and small pox) in the 6 weeks before treatment;
12. Receipt of non-live vaccine in the 4 weeks before treatment;
13. Any medical or psychological condition that in the opinion of the Sponsor Investigator would interfere with the safe completion of the trial;
14. Receipt of an investigational drug (including investigational vaccines) or used an invasive investigational medical device within 3 months or 5 half-lives before enrollment or is currently enrolled in the treatment stage of an investigational study;
15. Receipt of any immune-modulating biologic drug within 3 months of enrolling in the study.

Contacts and Locations

Locations

United States, Washington

Benaroya Research Institute

Seattle, Washington, United States, 98101

Sponsors and Collaborators

Carla Greenbaum, MD

Janssen Research & Development, LLC

Investigators

• Principal Investigator: Carla Greenbaum, MD; Benaroya Research Institute

  Study Documents (Full-Text)

Documents provided by Carla Greenbaum, MD, Benaroya Research Institute:

Study Protocol and Statistical Analysis Plan  [PDF] December 23, 2015

More Information

• Responsible Party: Carla Greenbaum, MD, Director, Diabetes Program, Benaroya Research Institute
• ClinicalTrials.gov Identifier: NCT02641522
• Other Study ID Numbers: EMU-002
• First Posted: December 29, 2015
• Results First Posted: October 9, 2018
• Last Update Posted: November 2, 2018
• Last Verified: October 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

Keywords provided by Carla Greenbaum, MD, Benaroya Research Institute:

T1D; Type 1 diabetes

Additional relevant MeSH terms:

Diabetes Mellitus; Diabetes Mellitus, Type 1; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Siltuximab; Antineoplastic Agents