Modulation of STAT3 Signaling With Siltuximab in Type 1 Diabetes
Study Details
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 |
|---|---|---|
| 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
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 Names:
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
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
-
Peak stimulated C-peptide level ≥ 0.1 pmol/mL following a mixed meal tolerance test (MMTT) conducted within 60 days of enrollment
-
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.
-
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.
-
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.
-
Willing and able to give informed consent for participation.
Exclusion Criteria:
-
History of severe reaction or anaphylaxis to human, humanized or murine monoclonal antibodies;
-
History of malignancy or serious uncontrolled cardiovascular disease or hypertension, nervous system, pulmonary, renal, or gastrointestinal disease, or significant dyslipidemia despite therapy;
-
Any history of recent (within 3 months) serious bacterial, viral, fungal, or other opportunistic infections;
-
History or serologic evidence of current or past HIV, Hepatitis B, or Hepatitis C;
-
Positive QuantiFERON or PPD TB test, history of tuberculosis, or active TB infection;
-
Active infection with EBV ;
-
Active infection with CMV;
-
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;
-
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
-
Females who are pregnant or lactating;
-
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;
-
Receipt of non-live vaccine in the 4 weeks before treatment;
-
Any medical or psychological condition that in the opinion of the Sponsor Investigator would interfere with the safe completion of the trial;
-
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;
-
Receipt of any immune-modulating biologic drug within 3 months of enrolling in the study.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | 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)
More Information
Publications
None provided.- EMU-002
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Siltuximab |
|---|---|
| Arm/Group Description | Single infusion of siltuximab (11 mg/kg) Siltuximab: Single infusion of siltuximab (11 mg/kg) |
| Period Title: Overall Study | |
| STARTED | 10 |
| COMPLETED | 10 |
| NOT COMPLETED | 0 |
Baseline Characteristics
| Arm/Group Title | Siltuximab |
|---|---|
| Arm/Group Description | Single infusion of siltuximab (11 mg/kg) Siltuximab: Single infusion of siltuximab (11 mg/kg) |
| Overall Participants | 10 |
| Age (Count of Participants) | |
| <=18 years |
0
0%
|
| Between 18 and 65 years |
10
100%
|
| >=65 years |
0
0%
|
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
27.1
(6.5)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
4
40%
|
| Male |
6
60%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |
| Hispanic or Latino |
0
0%
|
| Not Hispanic or Latino |
10
100%
|
| Unknown or Not Reported |
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |
| American Indian or Alaska Native |
0
0%
|
| Asian |
0
0%
|
| Native Hawaiian or Other Pacific Islander |
1
10%
|
| Black or African American |
0
0%
|
| White |
9
90%
|
| More than one race |
0
0%
|
| Unknown or Not Reported |
0
0%
|
| Region of Enrollment (participants) [Number] | |
| United States |
10
100%
|
Outcome Measures
| Title | Percent Change From Baseline in IL-6 Stimulated Intracellular p-STAT3 at Week 12 |
|---|---|
| Description | Change in IL-6 stimulated intracellular p-STAT3 between Week 12 and baseline |
| Time Frame | 0-to-12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| 1 participant was excluded from analysis because of technical problems with processing samples. |
| Arm/Group Title | Siltuximab |
|---|---|
| Arm/Group Description | Single infusion of siltuximab (11 mg/kg) Siltuximab: Single infusion of siltuximab (11 mg/kg) |
| Measure Participants | 9 |
| Mean (Standard Deviation) [Percent change from Baseline] |
-4.31
(15.99)
|
| Title | Adverse Event Monitoring |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
Adverse Events
| Time Frame | 0-to-12 weeks | |
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | Siltuximab | |
| Arm/Group Description | Single infusion of siltuximab (11 mg/kg) Siltuximab: Single infusion of siltuximab (11 mg/kg) | |
All Cause Mortality |
||
| Siltuximab | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/10 (0%) | |
Serious Adverse Events |
||
| Siltuximab | ||
| Affected / at Risk (%) | # Events | |
| Total | 1/10 (10%) | |
| Investigations | ||
| Nuetrophil count decreased | 1/10 (10%) | |
Other (Not Including Serious) Adverse Events |
||
| Siltuximab | ||
| Affected / at Risk (%) | # Events | |
| Total | 10/10 (100%) | |
| Gastrointestinal disorders | ||
| Gastroesophageal reflux disease | 1/10 (10%) | |
| Diarrhea | 1/10 (10%) | |
| Dental caries | 1/10 (10%) | |
| Infections and infestations | ||
| Upper respiratory infection | 3/10 (30%) | |
| Infections and infestations - Other - chalazion | 1/10 (10%) | |
| Investigations | ||
| Nuetrophil count decreased | 6/10 (60%) | |
| White blood cell decreased | 2/10 (20%) | |
| Lymphocyte count decreased | 2/10 (20%) | |
| Metabolism and nutrition disorders | ||
| Hypoglycemia | 1/10 (10%) | |
| Musculoskeletal and connective tissue disorders | ||
| Back pain | 1/10 (10%) | |
| Skin and subcutaneous tissue disorders | ||
| Rash maculo-papular | 1/10 (10%) | |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Sarah Robinson/ Administrative Assistant |
|---|---|
| Organization | Benaroya Research Institute |
| Phone | (206) 342-6931 |
| diabetes@benaroyaresearch.org |
- EMU-002