Type 1 DiabetesEarly Phase 1COBRANCT05281614
Immune Effects of Vedolizumab With or Without Anti-TNF Pre-treatment in T1D
A Early Phase 1 study testing Etanercept and Vedolizumab in people with Type 1 Diabetes, run by Benaroya Research Institute at 2 sites in United States.
Trial summary
The underlying hypothesis is that vedolizumab will modify immune cell trafficking in type 1 diabetes, and that this will be enhanced by pre-treatment with etanercept. This study will determine whether there is mechanistic evidence in support of this hypothesis and provide preliminary information about safety… Read more about this study
- Who is it for?
- Ages 18 to 45 years
- Conditions the study is for
- Type 1 Diabetes
- What is being tested?
- Etanercept and Vedolizumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 2 sitesUnited States
- Study dates
- 21 Sep 2022to 10 Jan 2024
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Males and females 18-45 years of age, inclusive
- Diagnosis of T1D between 21 days and 3 years from screening
- Positive for at least one diabetes-related autoantibody any time since diagnosis, including but not limited to:
- Glutamate decarboxylase (GAD-65)
- mIAA, if obtained within 10 days of the onset of exogenous insulin therapy
- IA-2
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- ZnT8 (Zinc transporter 8)
- Random (non-fasting) C-peptide or peak MMTT stimulated C-peptide ≥ 0.2 pmol/mL.
- Females of child-bearing potential must be willing to use effective birth control from the screening visit through 12 weeks post last dose of study medication.
- Up to date for clinically recommended immunizations including COVID-19 and seasonal influenza vaccine at least 3 weeks prior to baseline treatment.
- Willing to forgo live vaccines 6 weeks prior to baseline treatment visit until 6 weeks following last treatment visit.
- HbA1c ≤ 8.5% at screening
- Willing and able to give informed consent for participation
Who cannot join
- History of severe reaction or anaphylaxis to human, humanized or murine monoclonal antibodies
- History of malignancy or serious uncontrolled cardiovascular, nervous system, pulmonary, renal, or gastrointestinal disease
- History of immunodeficiency
- Recent (within 3 months) serious bacterial, viral, fungal, or other infections
- Pending or positive SARS-CoV-2 test or symptoms of possible COVID-19 illness at baseline treatment visit.
- Serologic evidence of current or past HIV, Hepatitis B, or Hepatitis C.
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- Positive QuantiFERON or PPD TB test, history of tuberculosis, or active TB infection.
- Active infection with EBV as defined by real-time polymerase chain reaction (PCR).
- Active infection with CMV as defined by real-time PCR.
- Clinically significant liver function abnormalities as defined by ALT or AST> 1.5 x the upper limit of age-determined normal (ULN).
- Any of the following hematologic abnormalities:
- White blood count <3,000/μL or >14,000/μL
- Lymphocyte count <800/μL
- Platelet count <75,000 /μL
- Hemoglobin <10.0 g/dL
- Neutrophil count <1500 cells/μL
- Females who are pregnant or lactating.
- Receipt of live vaccine (e.g., varicella, MMR (measles, mumps and rubella), intranasal influenza vaccine) within 6 weeks of randomization.
- Receipt of other vaccines within 3 weeks of baseline treatment.
- Receipt of an immune modulating biologic or investigational drug within 3 months or 5 half-lives before screening visit.
- Use of non-insulin therapies aimed to control hyperglycemia within 30 days of screening visit.
- History of other clinically significant autoimmune disease needing chronic therapy with biologics or steroids with the exception of celiac disease and stable thyroid disease.
- Use of medications known to influence glucose tolerance. Topical, nasal, inhaled corticosteroids acceptable per investigator discretion.
- Any medical or psychological condition that in the opinion of the principal investigator would interfere with the safe completion of the trial.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of California San Diego
La Jolla, California, 92037
Benaroya Research Institute
Seattle, Washington, 98102
About this study
The underlying hypothesis is that vedolizumab will modify immune cell trafficking in type 1 diabetes, and that this will be enhanced by pre-treatment with etanercept. This study will determine whether there is mechanistic evidence in support of this hypothesis and provide preliminary information about safety, efficacy, and tolerability of vedolizumab with and without pretreatment with etanercept in adults with type 1 diabetes (T1D)
Read the detailed description
Vedolizumab directly blocks integrin α4ß7 on circulating immune cells preventing their egress from the blood, while etanercept blocks the TNFα signaling necessary for the α4ß7 cognate addressin MAdCAM-1 to be expressed in pancreatic endothelial cells. For these reasons, the investigators hypothesize that the two agents may synergistically prevent diabetogenic immune cells from trafficking from the periphery to their target tissue to cause islet cell destruction. Cells from both the myeloid (e.g., myeloid DC1 cells and non-classical monocytes) and lymphoid compartments (e.g., diabetes antigen-specific T cells) would be impacted by this therapeutic combination.
- Conditions
- Type 1 Diabetes
- Being tested
- Etanercept, Vedolizumab
- Medical subject headings
- Diabetes Mellitus, Type 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EtanerceptDrug
Also called Enbrel
Etanercept is a fully humanized monoclonal antibody that targets TNFα.
VedolizumabDrug
Also called Entyvio
Vedolizumab is a humanized monoclonal antibody that targets α4ß7 integrin.
| Study group | Role | What they receive |
|---|---|---|
| Arm A | Experimental | Arm A will receive 6 weeks of vedolizumab after 8 weeks of etanercept. Final study visit at 52 weeks. Receives: Drug: Etanercept; Drug: Vedolizumab |
| Arm B | Experimental | Arm B will receive 6 weeks of vedolizumab only. Final study visit at 52 weeks. Receives: Drug: Vedolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Impact on insulin secretion determined by 2-hour MMTT stimulated AUC C-peptide 10 weeks after first vedolizumab dose and 52 weeks after randomization.
MMTT-Stimulated 2-Hour C-peptide AUC is the mean area under the C-peptide level time curve over the 2-hour period divided by the duration after a mixed-meal tolerance test.
Measured: baseline dose to 10 weeks and baseline dose to 52 weeks
Adverse events of etanercept treatment as a measure of safety and tolerability
An adverse event (AE) is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. Results will be reported as a rate of each adverse event
Measured: baseline to 52 weeks
Adverse events of vedolizumab treatment as a measure of safety and tolerability
An adverse event (AE) is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. Results will be reported as a rate of each adverse event
Measured: baseline to 52 weeks
Secondary outcomes (4)
Frequency of α4β7+ T cells
Cell phenotype will be measured as a percentage using either flow cytometry or cytometry by time of flight (CyTOF), via an assay such as the AIM (Activation-Induced Marker) assay.
Measured: baseline to 52 weeks
Frequency of myeloid DC1 cells
Cell phenotype will be measured as a percentage using either flow cytometry or cytometry by time of flight (CyTOF), via an assay such as the AIM (Activation-Induced Marker) assay.
Measured: baseline to 52 weeks
Frequency and surface marker phenotype of other immune cells such as antigen specific CD4 and CD8 cells, memory and naive T and B cells
Cell phenotype will be measured as a percentage using either flow cytometry or cytometry by time of flight (CyTOF), via an assay such as the AIM (Activation-Induced Marker) assay.
Measured: baseline to 52 weeks
Change in T1D antibody titers
T1D autoantibodies include: mIAA, GAD-65, IA-2, ZnT8, as reported in international units per mililiter
Measured: baseline to 52 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Mar 2022
- Study start21 Sep 2022
- Primary completion10 Jan 2024
- Study completion10 Jan 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type 1 DiabetesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- open label study with 2 treatment arms
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Benaroya Research Institute
- Sponsor type
- University, hospital or other
- Collaborators
- University of California, San Diego
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05281614
- Sponsor's protocol ID
- IRB22-007
- Acronym
- COBRA
- Status last verified
- Feb 2023
- First submitted
- 17 Feb 2022
- Last updated
- 24 May 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 24 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Immune Effects of Vedolizumab With or Without Anti-TNF Pre-treatment in T1D
- ClinicalTrials.gov ID
- NCT05281614
- Acronym / sponsor ID
- COBRA / IRB22-007
- Conditions
- Type 1 Diabetes
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Benaroya Research InstituteUniversity, hospital or other
- Collaborators
- University of California, San Diego
- Study start
- 21 Sep 2022 (actual)
- Primary completion
- 10 Jan 2024 (actual)
- Study completion
- 10 Jan 2024 (actual)
- First posted
- 16 Mar 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The underlying hypothesis is that vedolizumab will modify immune cell trafficking in type 1 diabetes, and that this will be enhanced by pre-treatment with etanercept. This study will determine whether there is mechanistic evidence in support of this hypothesis and provide preliminary information about safety, efficacy, and tolerability of vedolizumab with and without pretreatment with etanercept in adults with type 1 diabetes (T1D)
Detailed description
Vedolizumab directly blocks integrin α4ß7 on circulating immune cells preventing their egress from the blood, while etanercept blocks the TNFα signaling necessary for the α4ß7 cognate addressin MAdCAM-1 to be expressed in pancreatic endothelial cells. For these reasons, the investigators hypothesize that the two agents may synergistically prevent diabetogenic immune cells from trafficking from the periphery to their target tissue to cause islet cell destruction. Cells from both the myeloid (e.g., myeloid DC1 cells and non-classical monocytes) and lymphoid compartments (e.g., diabetes antigen-specific T cells) would be impacted by this therapeutic combination.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- open label study with 2 treatment arms
| Arm | Type | Receives |
|---|---|---|
| Arm A | Experimental | Drug: Etanercept, Drug: VedolizumabArm A will receive 6 weeks of vedolizumab after 8 weeks of etanercept. Final study visit at 52 weeks. |
| Arm B | Experimental | Drug: VedolizumabArm B will receive 6 weeks of vedolizumab only. Final study visit at 52 weeks. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (13 listed)
- Males and females 18-45 years of age, inclusive
- Diagnosis of T1D between 21 days and 3 years from screening
- Positive for at least one diabetes-related autoantibody any time since diagnosis, including but not limited to:
- Random (non-fasting) C-peptide or peak MMTT stimulated C-peptide ≥ 0.2 pmol/mL.
- Females of child-bearing potential must be willing to use effective birth control from the screening visit through 12 weeks post last dose of study medication.
Key exclusion criteria (24 listed)
- History of severe reaction or anaphylaxis to human, humanized or murine monoclonal antibodies
- History of malignancy or serious uncontrolled cardiovascular, nervous system, pulmonary, renal, or gastrointestinal disease
- History of immunodeficiency
- Recent (within 3 months) serious bacterial, viral, fungal, or other infections
- Pending or positive SARS-CoV-2 test or symptoms of possible COVID-19 illness at baseline treatment visit.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EtanerceptAlso: EnbrelEtanercept is a fully humanized monoclonal antibody that targets TNFα. | Drug | Arm A |
| VedolizumabAlso: EntyvioVedolizumab is a humanized monoclonal antibody that targets α4ß7 integrin. | Drug | Arm A, Arm B |
Primary outcome
Impact on insulin secretion determined by 2-hour MMTT stimulated AUC C-peptide 10 weeks after first vedolizumab dose and 52 weeks after randomization.
Time frame: baseline dose to 10 weeks and baseline dose to 52 weeks
MMTT-Stimulated 2-Hour C-peptide AUC is the mean area under the C-peptide level time curve over the 2-hour period divided by the duration after a mixed-meal tolerance test.
Adverse events of etanercept treatment as a measure of safety and tolerability
Time frame: baseline to 52 weeks
An adverse event (AE) is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. Results will be reported as a rate of each adverse event
Adverse events of vedolizumab treatment as a measure of safety and tolerability
Time frame: baseline to 52 weeks
An adverse event (AE) is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. Results will be reported as a rate of each adverse event
4 secondary outcomes
Frequency of α4β7+ T cells
Time frame: baseline to 52 weeks
Frequency of myeloid DC1 cells
Time frame: baseline to 52 weeks
Frequency and surface marker phenotype of other immune cells such as antigen specific CD4 and CD8 cells, memory and naive T and B cells
Time frame: baseline to 52 weeks
Change in T1D antibody titers
Time frame: baseline to 52 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 May 2024.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Etanercept and Vedolizumab in people with Type 1 Diabetes, run by Benaroya Research Institute at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Impact on insulin secretion determined by 2-hour MMTT stimulated AUC C-peptide 10 weeks after first vedolizumab dose and 52 weeks after randomization. (time frame: baseline dose to 10 weeks and baseline dose to 52 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 May 2024.