Baricitinib in New-onset Type 1 Diabetes (BANDIT)

A Phase 2, Randomised, Placebo Controlled Study Investigating the Efficacy of Baricitinib in New Onset Type 1 Diabetes Mellitus

Type 1 diabetes (T1D) results from the killing of insulin-producing pancreatic beta cells by cells of the immune system. The study aims to slow the progressive, immune-mediated loss of insulin-producing beta cells that occurs after clinical presentation. The investigators have identified a pathway that is important for immune cells to kill beta cells, and a drug that will block this pathway and prevent beta cell death. This drug, baricitinib, is already in clinical use for rheumatoid arthritis, and is currently in clinical trials for other diseases, including childhood autoimmune diseases. It is hypothesized that baricitinib treatment for 48 weeks will preserve beta cell function in children and young adults with recently-diagnosed T1D.

The trial aims to recruit 83 participants aged 10-30 years who have been recently diagnosed with T1D. Two thirds of the participants will be randomly assigned to receive baricitinib, one third will receive placebo. The trial will test if baricitinib can slow the progressive loss of insulin-producing beta cells in these patients. The primary objective is to determine if baricitinib can reduce the loss of meal-stimulated plasma C-peptide, a measure of beta-cell function. Maintaining endogenous insulin in recent-onset T1D improves glucose control and may lead to long-term improvements in glucose and lower rates of serious diabetes complications and death.

Study Overview

• Status: Active, not recruiting
• Conditions: Type 1 Diabetes
• Intervention / Treatment: Drug: Baricitinib; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 91
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • South Australia
    • North Adelaide, South Australia, Australia, 5006
      • Women's and Children's Hospital Adelaide
  • Victoria
    • Fitzroy, Victoria, Australia, 3065
      • St Vincent's Hospital Melbourne
    • Parkville, Victoria, Australia, 3050
      • Royal Melbourne Hospital
    • Parkville, Victoria, Australia, 3052
      • Royal Children's Hospital Melbourne

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 28 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female aged between 10 and 30 years (inclusive) at screening;
2. Diagnosis of T1D according to ADA criteria within 100 days prior to starting study drug;
3. Islet autoantibody positivity (one or more of: GADA, IA-2A, IAA (assessed within one week of commencing insulin therapy), ZnT8A);
4. Stimulated (peak or 90 min) C-peptide >0.2 nM during a 2-hour MMTT at the screening visit; or random C-peptide result >0.3 nM during the screening period.
5. Participants of childbearing age who are sexually active must agree to use of effective birth control until the end of the study;
6. Be able to read, understand and give written informed consent;
7. Be willing to comply with intensive diabetes management.

Exclusion Criteria:

1. Use of immunosuppressive or immunomodulatory therapies other than inhaled or topical glucocorticoids;
2. Current or past history of deep vein thrombosis or pulmonary embolism;
3. Impaired renal function defined by estimated glomerular filtration rate (according to the CKD-EPI) of < 60 mL/min/1.73 m2;
4. LDL cholesterol >4mmol/l;

5. Elevated liver function tests at screening:

   1. Aspartate aminotransferase 2x ULN
   2. Alanine aminotransferase 2 x ULN;

6. Clinically significant abnormal laboratory parameters at screening including but not limited to:

   1. Hemoglobin < 8 g/L;
   2. White blood cells <2500 cells/µl;
   3. Lymphocyte count <750 cells/µl;
   4. Platelets <50,000 cells/µl;
   5. Neutrophils <1200cells/µL;
7. Known hypersensitivity to baricitinib;
8. Known malignancy with the exception of successfully treated non- metastatic basal cell and squamous cell carcinoma;
9. Pregnancy, a desire for pregnancy, breast feeding, or a desire to father a child during the study;
10. Patients with current or recent (within 12 weeks of screening) clinically significant comorbidity, including clinically serious viral, bacterial, fungal, or parasitic infection. Viral infections include HBV, HCV, EBV, HIV, recent herpes zoster and TB;
11. Treatment with any investigational product within 30 days or 5 half - lives (whichever is longer) prior to baseline visit, or concurrent participation in a clinical trial with an investigational product or device;
12. Experienced any of the following within 12 weeks of screening: myocardial infarction, unstable ischemic heart disease, stroke, or New York Heart Association Stage IV heart failure;
13. Any serious medical condition within the previous 4 weeks which places the participant at an unacceptable risk if he or she were to participate in the study or confounds the ability to interpret data from the study, including, but not limited to, symptomatic cardiovascular, renal, respiratory, hepatic, gastrointestinal, endocrine, haematological and neurological conditions or psychiatric illness/social situations that would limit compliance with study requirements;
14. Have had any major surgery within 8 weeks prior to screening or will require major surgery during the study that, in the opinion of the investigator would pose an unacceptable risk to the participant;
15. History of chronic alcohol abuse or IV drug abuse or other illicit drug abuse within 2 years prior to screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Baricitinib; Baricitinib is an oral JAK1/JAK2-selective inhibitor. Dosage: The dose of baricitinib is 1 x 4mg tablet once daily Duration of administration: 48 weeks Mode of administration: Orally, with or without food	Drug: Baricitinib; Participants will take one tablet of study drug per day for 48 weeks, and will be followed up for 48 weeks after study drug treatment has finished. Two-thirds of participants will receive Baricitinib.
Placebo Comparator: Placebo; One placebo tablet once daily for a duration of 48 weeks. Placebo tablets contain lactose monohydrate, microcrystalline cellulose, croscarmellose sodium and magnesium stearate.	Drug: Placebo; Participants will take one tablet of study drug per day for 48 weeks, and will be followed up for 48 weeks after study drug treatment has finished. One-third of participants will receive Placebo.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The primary endpoint of the study is the change from baseline of plasma C-peptide area under the curve (AUC) over 2 hours following a mixed meal.	Measured at 48 weeks post commencement of intervention.

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in plasma C-peptide AUC over 2 hours following a mixed meal.	Measured at weeks 12, 24, 72 and 96 post commencement of intervention.
Change from baseline in mean daily insulin use over 7 consecutive days.	Measured during the 2 weeks prior to the assessment at weeks 12, 24, 48, 72 and 96 post commencement of intervention.
Change from baseline in glycosylated haemoglobin (HbA1c) levels.	Measured at weeks 12, 24, 48, 72 and 96 post commencement of intervention.
Number of participants with responder status. Responder status is defined as glycosylated haemoglobin (HbA1c) less than or equal to 6.5 percent and mean daily insulin use less than 0.5 international units per kilogram per day (IU/kg/day).	Measured at weeks 12, 24, 48, 72 and 96 post commencement of intervention.
Change in estimated C-peptide (CPEST) from baseline. CPEST is calculated based on six variable routine measures: disease duration, BMI, insulin dose, HbA1c, fasting plasma C-peptide and fasting plasma glucose.	Measured at weeks 12, 24, 48, 72 and 96 post commencement of intervention.
Continuous glucose monitoring (CGM).	Measured at baseline, 12, 24, 48 and 96 weeks post commencement of intervention.
The composite outcome assessing both the frequency, and when relevant, the severity of all adverse events.	Adverse events will be monitored throughout the entire study duration at weeks 0, 2, 4, 8, 12, 16, 20, 24, 36, 48, 72 and 96.

Collaborators and Investigators

• Sponsor: St Vincent's Institute of Medical Research
• Collaborators: Juvenile Diabetes Research Foundation; Juvenile Diabetes Research Foundation Australia
• Investigators: Principal Investigator: Tom Kay, Prof, SVI

Publications and helpful links

General Publications

• Waibel M, Thomas HE, Wentworth JM, Couper JJ, MacIsaac RJ, Cameron FJ, So M, Krishnamurthy B, Doyle MC, Kay TW. Investigating the efficacy of baricitinib in new onset type 1 diabetes mellitus (BANDIT)-study protocol for a phase 2, randomized, placebo controlled trial. Trials. 2022 May 23;23(1):433. doi: 10.1186/s13063-022-06356-z.

Helpful Links

• Trial website

Study record dates

Study Major Dates

• Study Start (Actual): October 30, 2020
• Primary Completion (Actual): January 30, 2023
• Study Completion (Estimated): March 31, 2024

Study Registration Dates

• First Submitted: February 22, 2021
• First Submitted That Met QC Criteria: February 25, 2021
• First Posted (Actual): March 1, 2021

Study Record Updates

• Last Update Posted (Actual): July 3, 2023
• Last Update Submitted That Met QC Criteria: June 28, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: newly diagnosed
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1
• Other Study ID Numbers: SVI-BARI-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All of the individual participant data collected during the trial, after de-identification.
• IPD Sharing Time Frame: Immediately following publication, and for at least 15 years after the end of the study.

IPD Sharing Access Criteria

The data will be made available on a case-by-case basis at the discretion of primary sponsor and only to researchers who have obtained ethical approval to access it.

Access is subject to approvals by the Principal Investigator, Prof Thomas Kay. Enquiries should be directed to tkay@svi.edu.au.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No