Type 1 Diabetes MellitusPhase 2EXTENDNCT02293837
Tocilizumab (TCZ) in New-onset Type 1 Diabetes
A Phase 2 study testing Tocilizumab (TCZ) in people with Type 1 Diabetes Mellitus and New-onset Type 1 Diabetes Mellitus, run by National Institute of Allergy and Infectious Diseases (NIAID) at 19 sites in 2 countries.
Trial summary
Type 1 diabetes mellitus (T1DM) is an autoimmune disease. Based on previous research, study doctors think that giving medicines to affect the immune system soon after diabetes is diagnosed may stop, delay or decrease the destruction of beta cells, resulting in better glucose control. Read more about this study
- Who is it for?
- Ages 6 to 17 years
- Conditions the study is for
- Type 1 Diabetes Mellitus, New-onset Type 1 Diabetes Mellitus, T1DM
- What is being tested?
- Tocilizumab (TCZ)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 136 participants
- Where
- 19 sitesin 2 countries
- Study dates
- 12 Mar 2015to 31 Aug 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 6 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Male or female aged 6-45 years*
- -Current Institutional Review Board (IRB)-approved age eligibility criteria is restricted to subjects 6 to 17 years of age at time of study enrollment
- Diagnosis of type 1 diabetes mellitus (T1DM), using the American Diabetes Association T1DM criteria, within 100 days of study enrollment
- Positive for at least one diabetes-related autoantibody, including but not limited to:
- Glutamate decarboxylase (GAD-65)
- Insulin, if obtained within 10 days of the onset of exogenous insulin therapy
Show all 10Show fewer
- Insulinoma antigen-2 (IA-2)
- Zinc transporter-8 (ZnT8)
- Peak stimulated C-peptide level ≥ 0.2 pmol/mL following a mixed-meal tolerance test (MMTT) conducted at least 21 days from diagnosis and within 37 days of randomization (V0)
- Signed informed consent (and informed assent of minor, if applicable).
Who cannot join
- 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, or significant dyslipidemia
- Any history of recent serious bacterial, viral, fungal, or other opportunistic infections
- Have serologic evidence of current or past HIV (Human immunodeficiency virus), Hepatitis B, or Hepatitis C
- Positive QuantiFERON Tuberculosis (TB) test, history of TB, or active TB infection
- Active infection with Epstein-Barr virus (EBV) as defined by EBV viral load ≥10,000 copies per mL of whole blood
Show all 25Show fewer
- Active infection with Cytomegalovirus (CMV) as defined by CMV viral load ≥10,000 copies per mL of whole blood
- Diagnosis of liver disease or elevated hepatic enzymes, as defined by Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), or both > 1.5 x the upper limit of age-determined normal (ULN) or total bilirubin > ULN
- Current or prior treatment that is known to cause a significant, ongoing change in the course of T1D or immunologic status
- Current or prior (within last 30 days) use of drugs other than insulin to treat hyperglycemia (e.g. metformin, sulfonylureas, glinides, thiazolidinediones, exenatide, liraglutide, Dipeptidyl peptidase-4 Intravenous (DPP-IV) inhibitors, or amylin)
- Current use of any medication known to significantly influence glucose tolerance (e.g., atypical antipsychotics, diphenylhydantoin, niacin)
- Any of the following hematologic abnormalities, confirmed by repeat tests:
- White blood count <3,000/microL or >14,000/microL
- Lymphocyte count <500/microL
- Platelet count <150,000 /microL
- Hemoglobin <8.5 g/dL
- . Neutrophil count <2,000 cells/microL.
- Females who are pregnant, lactating, or planning on pregnancy during the 2- year study period
- History or diagnoses of other autoimmune diseases with the exception of stable thyroid or celiac disease
- History of alcohol, drug or chemical abuse within 1 year prior to study eligibility screening evaluation
- Any medical or psychological condition that in the opinion of the principal investigator would interfere with safe completion of the trial
- Prior participation in a clinical trial that could increase risks associated with this clinical trial
- 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 randomization
- High lipid levels (fasting Low-density lipoprotein (LDL) cholesterol ≥160 mg/dL)
- History of significant allergy (e.g. anaphylaxis) to milk or soy proteins.
Trial locations and contacts
19 sites in 2 countries.
19 sites in 2 countries
United States17 sites
Harvard University, Joslin Diabetes Center
Boston, Massachusetts, 002215
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
University of Florida
Gainesville, Florida, 32610
Indiana University Health - Riley Hospital for Children
Indianapolis, Indiana, 46202
University of Iowa
Iowa City, Iowa, 52242
Children's Mercy Hospital
Kansas City, Missouri, 64111
University of Miami: Diabetes Research Institute
Miami, Florida, 33136
University of Minnesota
Minneapolis, Minnesota, 55455
Vanderbilt University
Nashville, Tennessee, 37232
Yale University School of Medicine: Diabetes Endocrinology Research Center
New Haven, Connecticut, 06519
Columbia University, Naomi Berrie Diabetes Center
New York, New York, 10032
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
University of California San Francisco
San Francisco, California, 94143
Benaroya Research Institute
Seattle, Washington, 98101
Sanford Research
Sioux Falls, South Dakota, 57104
Stanford University
Stanford, California, 94305
University of South Florida: Diabetes Center
Tampa, Florida, 33612
Australia2 sites
Lady Cilento Children's Hospital: Department of Endocrinology
South Brisbane, Queensland, 4101
The Children's Hospital at Westmead: Kids Research Institute
Westmead, New South Wales, Westmead 2145
About this study
Official title: Preserving Beta-Cell Function With Tocilizumab in New-onset Type 1 Diabetes (ITN058AI)
Type 1 diabetes mellitus (T1DM) is an autoimmune disease. Based on previous research, study doctors think that giving medicines to affect the immune system soon after diabetes is diagnosed may stop, delay or decrease the destruction of beta cells, resulting in better glucose control.
Researchers believe that tocilizumab could have some effect on the cells in the immune system that are thought to be involved in the development of type 1 diabetes. This study will test whether tocilizumab can help preserve or delay destruction of remaining beta cells in people recently diagnosed type 1 diabetes.
Read the detailed description
Staggered enrollment is planned for this trial.
Prior to initiating the study in the pediatric age group (6-17 years old), 30-99 eligible adults (ages 18-45 years) will be randomized 2:1 to tocilizumab or placebo, respectively. Once the first thirty adult participants have completed 12 weeks of treatment, the FDA and Data and Safety Monitoring Board (DSMB) will review available data (e.g., interim analysis) to weigh potential risks and benefits before opening the trial to pediatric participants.
As of ≥ May 15, 2017: Study enrollment limited to participants ages 6 to 17 years inclusive.
- Being tested
- Tocilizumab (TCZ), Placebo, Standard of Care
- Keywords
- interleukin-6 (IL-6) receptor inhibitor
- 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.
Tocilizumab (TCZ)Drug
Also called Actemra®
Subjects assigned to this group will receive tocilizumab intravenous (IV) infusions of either 8.0 mg/kg (body weight ≥ 30kg) or 10.0 mg/kg (body weight <30kg) every 4 weeks for 24 weeks.
PlaceboDrug
Also called Placebo for Tocilizumab
Subjects assigned to this group will receive placebo intravenous (IV) infusions of either 8.0 mg/kg (body weight ≥ 30kg) or 10.0 mg/kg (body weight <30kg) every 4 weeks for 24 weeks.
Standard of CareOther
Also called SOC
Participants will also receive standard intensive diabetes management (in accordance with the American Diabetes Association guidelines [Standard of Care, SOC])
| Study group | Role | What they receive |
|---|---|---|
| Tocilizumab (TCZ) + SOC | Experimental | Subjects will receive intravenous (IV) infusions of either 8.0 mg/kg (body weight ≥30 kg) or 10.0 mg/kg (body weight <30kg) tocilizumab every 4 weeks for 24 weeks. Participants will also receive standard intensive diabetes management (in accordance with the American Diabetes Association guidelines [Standard of Care, SOC]) Receives: Drug: Tocilizumab (TCZ); Other: Standard of Care |
| Tocilizumab Placebo Group + SOC | Placebo comparator | Subjects will receive IV infusions of either 8.0 mg/kg (body weight ≥ 30kg) or 10.0 mg/kg (body weight <30kg) placebo every 4 weeks for 24 weeks. Participants will also receive standard intensive diabetes management (in accordance with the American Diabetes Association guidelines [Standard of Care, SOC]) Receives: Drug: Placebo; Other: Standard of Care |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in 2-Hour C-peptide Mean Area Under the Curve (mAUC) in Pediatric Participants
C-peptide is a substance released by the pancreas into the bloodstream in equal amounts to insulin and reflects how much insulin pancreatic beta cells are making. The standardized MMTT evaluates whether beta cells are producing endogenous insulin. The MMTT was performed in the morning and blood samples for C-peptide collected at baseline (pre-meal) and 15, 30, 60, 90, 120, 150, 180, 210, and 240 minutes post-meal. C-peptide mAUC was calculated using the trapezoidal rule over the 2-hour time period. Larger numbers are preferable (better) in these mAUC results: more insulin being produced reflects less severe disease. C-peptide levels in the serum (e.g., mAUC following a standardized MMTT) compared to control group at 1 year post treatment initiation for the evaluation of investigational products intended to preserve endogenous beta-cell function in T1DM trials is recognized by the Center for Drug Evaluation and Research (CDER) at the FDA as a valid efficacy endpoint.
Measured: Baseline (Pre-treatment) to Week 52
Secondary outcomes (10)
Change From Baseline in 2-Hour C-peptide Mean Area Under the Curve (mAUC)
C-peptide is a substance released by the pancreas into the bloodstream in equal amounts to insulin and reflects how much insulin pancreatic beta cells are making. The standardized MMTT evaluates whether beta cells are producing endogenous insulin. The MMTT was performed in the morning and blood samples for C-peptide collected at baseline (pre-meal) and 15, 30, 60, 90, 120, 150, 180, 210, and 240 minutes post-meal. C-peptide mAUC was calculated using the trapezoidal rule over the 2-hour time period. Larger numbers are preferable (better) in these mAUC results: more insulin being produced reflects less severe disease. C-peptide levels in the serum (e.g., mAUC following a standardized MMTT) compared to control group at 1 year post treatment initiation for the evaluation of investigational products intended to preserve endogenous beta-cell function in T1DM trials is recognized by the Center for Drug Evaluation and Research (CDER) at the FDA as a valid efficacy endpoint.
Measured: Baseline (Pre-treatment) to Weeks 24, 52, and 104
2-Hour C-peptide Mean Area Under the Curve (mAUC), Mixed Model
C-peptide is a substance released by the pancreas into the bloodstream in equal amounts to insulin and reflects how much insulin pancreatic beta cells are making. The standardized MMTT evaluates whether beta cells are producing endogenous insulin. The MMTT was performed in the morning and blood samples for C-peptide collected at baseline (pre-meal) and 15, 30, 60, 90, 120, 150, 180, 210, and 240 minutes post-meal. C-peptide mAUC was calculated using the trapezoidal rule over the 2-hour time period. Larger numbers are preferable (better) in these mAUC results: more insulin being produced reflects less severe disease. C-peptide levels in the serum (e.g., mAUC following a standardized MMTT) compared to control group at 1 year post treatment initiation for the evaluation of investigational products intended to preserve endogenous beta-cell function in T1DM trials is recognized by the Center for Drug Evaluation and Research (CDER) at the FDA as a valid efficacy endpoint.
Measured: Baseline (Pre-treatment), Weeks 12, 24, 39, 52, 78, and 104
Change From Baseline in 4-Hour C-peptide Mean Area Under the Curve (mAUC)
C-peptide is a substance released by the pancreas into the bloodstream in equal amounts to insulin and reflects how much insulin pancreatic beta cells are making. The standardized MMTT evaluates whether beta cells are producing endogenous insulin. The MMTT was performed in the morning and blood samples for C-peptide collected at baseline (pre-meal) and 15, 30, 60, 90, 120, 150, 180, 210, and 240 minutes post-meal. C-peptide mAUC was calculated using the trapezoidal rule over the 4-hour time period. Larger numbers are preferable (better) in these mAUC results: more insulin being produced reflects less severe disease. C-peptide levels in the serum (e.g., mAUC following a standardized MMTT) compared to control group at 1 year post treatment initiation for the evaluation of investigational products intended to preserve endogenous beta-cell function in T1DM trials is recognized by the Center for Drug Evaluation and Research (CDER) at the FDA as a valid efficacy endpoint.
Measured: Baseline (Pre-treatment) to Weeks 52 and 104
Change From Baseline in Average Insulin Use in Units Per Kilogram Body Weight Per Day
The need to use exogenous insulin is an indication that the body is not producing enough endogenous insulin. Higher amounts of insulin use indicate higher disease activity. Insulin use was collected each day for 5 days prior to the visit. Average insulin use per kg is the average insulin use over the 5 days prior to the visit divided by the participant's weight in kg.
Measured: Baseline (Pre-treatment) to Weeks 24, 52, and 104
Change From Baseline in Average Insulin Use Per Kg, Mixed Model
The need to use exogenous insulin is an indication that the body is not producing enough endogenous insulin. Higher amounts of insulin use indicate higher disease activity. Insulin use was collected each day for 5 days prior to the visit. Average insulin use per kg is the average insulin use over the 5 days prior to the visit divided by the participant's weight in kg.
Measured: Baseline (Pre-treatment) to Weeks 12, 24, 39, 52, 78, and 104
Change From Baseline in Hemoglobin A1c
Glycosylated hemoglobin (HbA1c) is a measure of the average plasma concentration of blood sugar (glucose) over the previous three months and measures the level of optimal management of underlying disease. An HbA1c of 5.6% or less is considered normal. HbA1c of 6.5% or higher is typical for individuals with Type 1 Diabetes mellitus (T1DM). The closer HbA1c levels are to normal, the better controlled the disease is.
Measured: Baseline (Pre-treatment) to Weeks 24, 52, and 104
Change From Baseline in Hemoglobin A1C (HbA1c) Level in Participants, Mixed Model
Glycosylated hemoglobin (HbA1c) is a measure of the average plasma concentration of blood sugar (glucose) over the previous three months and measures the level of optimal management of underlying disease. An HbA1c of 5.6% or less is considered normal. HbA1c of 6.5% or higher is typical for individuals with Type 1 Diabetes mellitus (T1DM). The closer HbA1c levels are to normal, the better controlled the disease is.
Measured: Baseline (Pre-treatment) to Weeks 12, 24, 39, 52, 78, and 104
Number of Participants Who Experienced at Least One Major Hypoglycemic Event After Treatment Initiation
Major hypoglycemic adverse events are defined as: Blood glucose concentration < 40 mg/dL (Grades 3-5, NCI-CTCAE version 4.03*), or hypoglycemic events involving seizure or loss of consciousness (coma) or requiring assistance from another individual in order to recover.
*NCI-CTCAE: National Cancer Institute Common Terminology Criteria for Adverse Events
Measured: Day 0 (Treatment Initiation) to Weeks 52 and 104
Number of Participants Who Experienced Infusion-Related Adverse Events
An infusion/dose reaction is defined as an adverse event occurring during and within 24 hours after the infusion or subcutaneous injection of tocilizumab. This may include hypersensitivity reactions or anaphylactic reactions.
Measured: Day 0 (Treatment Initiation) to Week 52
Number of Participants Who Experienced Hypersensitivity Adverse Events
Signs of a possible hypersensitivity reaction to the study drug include but are not limited to:
- Fever, chills, pruritus, urticaria, angioedema, and skin rash
- Cardiopulmonary reactions, including chest pain, dyspnea, hypotension or hypertension
Measured: Day 0 (Treatment Initiation) to Week 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Nov 2014 (estimated)
- Study start12 Mar 2015
- Primary completion10 Jul 2019
- Study completion31 Aug 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Type 1 Diabetes MellitusStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- 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
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 136 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- Immune Tolerance Network (ITN), PPD Development, LP, Rho Federal Systems Division, Inc.
- Responsible party
- Sponsor
- Investigators
- Carla Greenbaum, Study chair, Benaroya Research Institute at Virginia Mason: Diabetes Research ProgramJane Buckner, M.D., Study chair, Benaroya Research Institute at Virginia Mason: Diabetes Research Program
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02293837
- Sponsor's protocol ID
- DAIT ITN058AI
- Acronym
- EXTEND
- Status last verified
- Aug 2021
- First submitted
- 13 Nov 2014
- Last updated
- 8 Sep 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: The plan is to share data upon completion of the study in: Immunology Database and Analysis Portal (ImmPort), a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts.
Publications
Greenbaum CJ, Serti E, Lambert K, Weiner LJ, Kanaparthi S, Lord S, Gitelman SE, Wilson DM, Gaglia JL, Griffin KJ, Russell WE, Raskin P, Moran A, Willi SM, Tsalikian E, DiMeglio LA, Herold KC, Moore WV, Goland R, Harris M, Craig ME, Schatz DA, Baidal DA, Rodriguez H, Utzschneider KM, Nel HJ, Soppe CL, Boyle KD, Cerosaletti K, Keyes-Elstein L, Long SA, Thomas R, McNamara JG, Buckner JH, Sanda S; ITN058AI EXTEND Study Team. IL-6 receptor blockade does not slow beta cell loss in new-onset type 1 diabetes. JCI Insight. 2021 Nov 8;6(21):e150074. doi: 10.1172/jci.insight.150074.
PubMed 34747368Hundhausen C, Roth A, Whalen E, Chen J, Schneider A, Long SA, Wei S, Rawlings R, Kinsman M, Evanko SP, Wight TN, Greenbaum CJ, Cerosaletti K, Buckner JH. Enhanced T cell responses to IL-6 in type 1 diabetes are associated with early clinical disease and increased IL-6 receptor expression. Sci Transl Med. 2016 Sep 14;8(356):356ra119. doi: 10.1126/scitranslmed.aad9943.
PubMed 27629486
Study at a glance
From the registry record, last updated by the sponsor on 8 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Preserving Beta-Cell Function With Tocilizumab in New-onset Type 1 Diabetes (ITN058AI)
- ClinicalTrials.gov ID
- NCT02293837
- Acronym / sponsor ID
- EXTEND / DAIT ITN058AI
- Keywords
- interleukin-6 (IL-6) receptor inhibitor
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 136 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Collaborators
- Immune Tolerance Network (ITN), PPD Development, LP, Rho Federal Systems Division, Inc.
- Study start
- 12 Mar 2015 (actual)
- Primary completion
- 10 Jul 2019 (actual)
- Study completion
- 31 Aug 2020 (actual)
- First posted
- 18 Nov 2014 (estimated)
- Results
- Posted 17 Aug 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Type 1 diabetes mellitus (T1DM) is an autoimmune disease. Based on previous research, study doctors think that giving medicines to affect the immune system soon after diabetes is diagnosed may stop, delay or decrease the destruction of beta cells, resulting in better glucose control.
Researchers believe that tocilizumab could have some effect on the cells in the immune system that are thought to be involved in the development of type 1 diabetes. This study will test whether tocilizumab can help preserve or delay destruction of remaining beta cells in people recently diagnosed type 1 diabetes.
Detailed description
Staggered enrollment is planned for this trial.
Prior to initiating the study in the pediatric age group (6-17 years old), 30-99 eligible adults (ages 18-45 years) will be randomized 2:1 to tocilizumab or placebo, respectively. Once the first thirty adult participants have completed 12 weeks of treatment, the FDA and Data and Safety Monitoring Board (DSMB) will review available data (e.g., interim analysis) to weigh potential risks and benefits before opening the trial to pediatric participants.
As of ≥ May 15, 2017: Study enrollment limited to participants ages 6 to 17 years inclusive.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tocilizumab (TCZ) + SOC | Experimental | Drug: Tocilizumab (TCZ), Other: Standard of CareSubjects will receive intravenous (IV) infusions of either 8.0 mg/kg (body weight ≥30 kg) or 10.0 mg/kg (body weight <30kg) tocilizumab every 4 weeks for 24 weeks. Participants will also receive standard intensive diabetes management (in accordance with the American Diabetes Association guidelines [Standard of Care, SOC]) |
| Tocilizumab Placebo Group + SOC | Placebo comparator | Drug: Placebo, Other: Standard of CareSubjects will receive IV infusions of either 8.0 mg/kg (body weight ≥ 30kg) or 10.0 mg/kg (body weight <30kg) placebo every 4 weeks for 24 weeks. Participants will also receive standard intensive diabetes management (in accordance with the American Diabetes Association guidelines [Standard of Care, SOC]) |
Who may qualify
- Ages
- 6 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (10 listed)
- Male or female aged 6-45 years*
- -Current Institutional Review Board (IRB)-approved age eligibility criteria is restricted to subjects 6 to 17 years of age at time of study enrollment
- Diagnosis of type 1 diabetes mellitus (T1DM), using the American Diabetes Association T1DM criteria, within 100 days of study enrollment
- Positive for at least one diabetes-related autoantibody, including but not limited to:
- Peak stimulated C-peptide level ≥ 0.2 pmol/mL following a mixed-meal tolerance test (MMTT) conducted at least 21 days from diagnosis and within 37 days of randomization (V0)
Key exclusion criteria (25 listed)
- 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, or significant dyslipidemia
- Any history of recent serious bacterial, viral, fungal, or other opportunistic infections
- Have serologic evidence of current or past HIV (Human immunodeficiency virus), Hepatitis B, or Hepatitis C
- Positive QuantiFERON Tuberculosis (TB) test, history of TB, or active TB infection
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 |
|---|---|---|
| Tocilizumab (TCZ)Also: Actemra®Subjects assigned to this group will receive tocilizumab intravenous (IV) infusions of either 8.0 mg/kg (body weight ≥ 30kg) or 10.0 mg/kg (body weight <30kg) every 4 weeks for 24 weeks. | Drug | Tocilizumab (TCZ) + SOC |
| PlaceboAlso: Placebo for TocilizumabSubjects assigned to this group will receive placebo intravenous (IV) infusions of either 8.0 mg/kg (body weight ≥ 30kg) or 10.0 mg/kg (body weight <30kg) every 4 weeks for 24 weeks. | Drug | Tocilizumab Placebo Group + SOC |
| Standard of CareAlso: SOCParticipants will also receive standard intensive diabetes management (in accordance with the American Diabetes Association guidelines [Standard of Care, SOC]) | Other | Tocilizumab (TCZ) + SOC, Tocilizumab Placebo Group + SOC |
Primary outcome
Change From Baseline in 2-Hour C-peptide Mean Area Under the Curve (mAUC) in Pediatric Participants
Time frame: Baseline (Pre-treatment) to Week 52
C-peptide is a substance released by the pancreas into the bloodstream in equal amounts to insulin and reflects how much insulin pancreatic beta cells are making. The standardized MMTT evaluates whether beta cells are producing endogenous insulin. The MMTT was performed in the morning and blood samples for C-peptide collected at baseline (pre-meal) and 15, 30, 60, 90, 120, 150, 180, 210, and 240 minutes post-meal. C-peptide mAUC was calculated using the trapezoidal rule over the 2-hour time period. Larger numbers are preferable (better) in these mAUC results: more insulin being produced reflects less severe disease. C-peptide levels in the serum (e.g., mAUC following a standardized MMTT) compared to control group at 1 year post treatment initiation for the evaluation of investigational products intended to preserve endogenous beta-cell function in T1DM trials is recognized by the Center for Drug Evaluation and Research (CDER) at the FDA as a valid efficacy endpoint.
10 secondary outcomes
Change From Baseline in 2-Hour C-peptide Mean Area Under the Curve (mAUC)
Time frame: Baseline (Pre-treatment) to Weeks 24, 52, and 104
2-Hour C-peptide Mean Area Under the Curve (mAUC), Mixed Model
Time frame: Baseline (Pre-treatment), Weeks 12, 24, 39, 52, 78, and 104
Change From Baseline in 4-Hour C-peptide Mean Area Under the Curve (mAUC)
Time frame: Baseline (Pre-treatment) to Weeks 52 and 104
Change From Baseline in Average Insulin Use in Units Per Kilogram Body Weight Per Day
Time frame: Baseline (Pre-treatment) to Weeks 24, 52, and 104
Change From Baseline in Average Insulin Use Per Kg, Mixed Model
Time frame: Baseline (Pre-treatment) to Weeks 12, 24, 39, 52, 78, and 104
Change From Baseline in Hemoglobin A1c
Time frame: Baseline (Pre-treatment) to Weeks 24, 52, and 104
Change From Baseline in Hemoglobin A1C (HbA1c) Level in Participants, Mixed Model
Time frame: Baseline (Pre-treatment) to Weeks 12, 24, 39, 52, 78, and 104
Number of Participants Who Experienced at Least One Major Hypoglycemic Event After Treatment Initiation
Time frame: Day 0 (Treatment Initiation) to Weeks 52 and 104
Number of Participants Who Experienced Infusion-Related Adverse Events
Time frame: Day 0 (Treatment Initiation) to Week 52
Number of Participants Who Experienced Hypersensitivity Adverse Events
Time frame: Day 0 (Treatment Initiation) to Week 52
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Sep 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34747368Greenbaum CJ, Serti E, Lambert K, Weiner LJ, Kanaparthi S, Lord S, Gitelman SE, Wilson DM, Gaglia JL, Griffin KJ, Russell WE, Raskin P, Moran A, Willi SM, Tsalikian E, DiMeglio LA, Herold KC, Moore WV, Goland R, Harris M, Craig ME, Schatz DA, Baidal DA, Rodriguez H, Utzschneider KM, Nel HJ, Soppe CL, Boyle KD, Cerosaletti K, Keyes-Elstein L, Long SA, Thomas R, McNamara JG, Buckner JH, Sanda S; ITN058AI EXTEND Study Team. IL-6 receptor blockade does not slow beta cell loss in new-onset type 1 diabetes. JCI Insight. 2021 Nov 8;6(21):e150074. doi: 10.1172/jci.insight.150074.
- Derived from this study: PubMed 27629486Hundhausen C, Roth A, Whalen E, Chen J, Schneider A, Long SA, Wei S, Rawlings R, Kinsman M, Evanko SP, Wight TN, Greenbaum CJ, Cerosaletti K, Buckner JH. Enhanced T cell responses to IL-6 in type 1 diabetes are associated with early clinical disease and increased IL-6 receptor expression. Sci Transl Med. 2016 Sep 14;8(356):356ra119. doi: 10.1126/scitranslmed.aad9943.
- National Institute of Allergy and Infectious Diseases (NIAID) websiteLink provided by the sponsor.
- Division of Allergy, Immunology, and Transplantation (DAIT) websiteLink provided by the sponsor.
- Immune Tolerance Network (ITN) websiteLink provided by the sponsor.
- EXTEND's study-specific ITN websiteLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. The plan is to share data upon completion of the study in: Immunology Database and Analysis Portal (ImmPort), a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts.
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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.
Carla Greenbaum study chair
Benaroya Research Institute at Virginia Mason: Diabetes Research Program
Jane Buckner, M.D. study chair
Benaroya Research Institute at Virginia Mason: Diabetes Research Program
19 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tocilizumab (TCZ) in people with Type 1 Diabetes Mellitus and New-onset Type 1 Diabetes Mellitus, run by National Institute of Allergy and Infectious Diseases (NIAID) at 19 sites in 2 countries.
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 10 inclusion and 25 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 8 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 19 sites in United States, Australia. 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. Some participants in this study may receive a placebo. 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?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Aug 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Change From Baseline in 2-Hour C-peptide Mean Area Under the Curve (mAUC) in Pediatric Participants (time frame: Baseline (Pre-treatment) to Week 52). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02293837, which also lists 2 linked publications.
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 8 Sep 2021.