Type 1 Diabetes
Conditions
Keywords
T1D, Type 1 diabetes
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.
Interventions
DRUGSiltuximab
Single infusion of siltuximab (11 mg/kg)
Sponsors
Janssen Research & Development, LLC
Carla Greenbaum, MD
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in IL-6 Stimulated Intracellular p-STAT3 at Week 12 | 0-to-12 weeks | Change in IL-6 stimulated intracellular p-STAT3 between Week 12 and baseline |
Other
| Measure | Time frame | Description |
|---|---|---|
| Adverse Event Monitoring | 0-to-12 weeks | Monitor adverse events associated with siltuximab treatment. All AE related to study drug will be tabulated along with their grade. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Siltuximab Single infusion of siltuximab (11 mg/kg)
Siltuximab: Single infusion of siltuximab (11 mg/kg) | 10 |
| Total | 10 |
Baseline characteristics
| Characteristic | Siltuximab |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants |
| Age, Continuous | 27.1 years STANDARD_DEVIATION 6.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 9 Participants |
| Region of Enrollment United States | 10 participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 10 |
| other Total, other adverse events | 10 / 10 |
| serious Total, serious adverse events | 1 / 10 |
Outcome results
Primary
Percent Change From Baseline in IL-6 Stimulated Intracellular p-STAT3 at Week 12
Change in IL-6 stimulated intracellular p-STAT3 between Week 12 and baseline
Time frame: 0-to-12 weeks
Population: 1 participant was excluded from analysis because of technical problems with processing samples.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Siltuximab | Percent Change From Baseline in IL-6 Stimulated Intracellular p-STAT3 at Week 12 | -4.31 Percent change from Baseline | Standard Deviation 15.99 |
Other Pre-specified
Adverse Event Monitoring
Monitor adverse events associated with siltuximab treatment. All AE related to study drug will be tabulated along with their grade.
Time frame: 0-to-12 weeks