Clinical trial NCT02641522: Modulation of STAT3 Signaling With Siltuximab in Type 1 Diabetes
Official title: Modulation of STAT3 Signaling With Siltuximab in Type 1 Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Type 1 Diabetes
Keywords: T1D
Type 1 diabetes
Lead sponsor: Benaroya Research Institute
Sponsor class: OTHER
Collaborators: name: Janssen Research & Development, LLC
First posted: 2015-12-29
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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).

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.

Eligibility 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.

Primary outcomes:
measure: Percent Change From Baseline in IL-6 Stimulated Intracellular p-STAT3 at Week 12
timeFrame: 0-to-12 weeks
Secondary outcomes:
Other outcomes:
measure: Adverse Event Monitoring
timeFrame: 0-to-12 weeks
Locations:
city: Seattle
country: United States
facility: Benaroya Research Institute
state: Washington
Study officials:
affiliation: Benaroya Research Institute
name: Carla Greenbaum, MD
role: PRINCIPAL_INVESTIGATOR
References: