Baricitinib in New-onset Type 1 Diabetes (BANDIT)

• ClinicalTrials.gov Identifier: NCT04774224
• Recruitment Status: Recruiting
• First Posted: March 1, 2021
• Last Update Posted: March 1, 2021
• Sponsor: St Vincent's Institute of Medical Research
• Collaborators: Juvenile Diabetes Research Foundation; Juvenile Diabetes Research Foundation Australia
• Information provided by (Responsible Party): St Vincent's Institute of Medical Research

Study Description

Brief Summary:

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 12-30 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.

Condition or disease	Intervention/treatment	Phase
Type 1 Diabetes	Drug: Baricitinib; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 83 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Randomised placebo controlled trial
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Prior to study initiation, an independent researcher is responsible for generating the randomization schedule. The randomization schedule including treatment group assignment (active or placebo) will be provided to the pharmacists at each one of the study sites. The study pharmacists will conceal the group assignment from study participants, investigators and study staff including the statistician.
• Primary Purpose: Treatment
• Official Title: A Phase 2, Randomised, Placebo Controlled Study Investigating the Efficacy of Baricitinib in New Onset Type 1 Diabetes Mellitus
• Actual Study Start Date: October 30, 2020
• Estimated Primary Completion Date: October 31, 2023
• Estimated Study Completion Date: October 31, 2024

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. 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. [ Time Frame: Measured at 48 weeks post commencement of intervention. ]

Secondary Outcome Measures :

1. Change from baseline in plasma C-peptide AUC over 2 hours following a mixed meal. [ Time Frame: Measured at weeks 12, 24, 72 and 96 post commencement of intervention. ]
2. Change from baseline in mean daily insulin use over 7 consecutive days. [ Time Frame: Measured during the 2 weeks prior to the assessment at weeks 12, 24, 48, 72 and 96 post commencement of intervention. ]
3. Change from baseline in glycosylated haemoglobin (HbA1c) levels. [ Time Frame: Measured at weeks 12, 24, 48, 72 and 96 post commencement of intervention. ]
4. 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). [ Time Frame: Measured at weeks 12, 24, 48, 72 and 96 post commencement of intervention. ]
5. 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. [ Time Frame: Measured at weeks 12, 24, 48, 72 and 96 post commencement of intervention. ]
6. Continuous glucose monitoring (CGM). [ Time Frame: Measured at baseline, 12, 24, 48 and 96 weeks post commencement of intervention. ]
7. The composite outcome assessing both the frequency, and when relevant, the severity of all adverse events. [ Time Frame: 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. ]

Eligibility Criteria

• Ages Eligible for Study: 12 Years to 30 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Male or female aged between 12 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;
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.

Contacts and Locations

Contacts

Contact: Michaela Waibel, PhD; +61 (03) 9231 2502; mwaibel@svi.edu.au

Locations

Australia, South Australia

Women's and Children's Hospital Adelaide; Recruiting

North Adelaide, South Australia, Australia, 5006

Contact: Mandy Anderson +61 (0)8 8313 1410 mandy.anderson@adelaide.edu.au

Principal Investigator: Jennifer Couper, Prof

Australia, Victoria

St Vincent's Hospital Melbourne; Recruiting

Fitzroy, Victoria, Australia, 3065

Contact: Elizabeth Mulrooney +61 (0)3 9231 3675 Elizabeth.Mulrooney@svha.org.au

Principal Investigator: Richard MacIsaac, Prof

Royal Melbourne Hospital; Recruiting

Parkville, Victoria, Australia, 3050

Contact: Candice Hall +61 (0)3 9345 2369 Candice.Hall@mh.org.au

Principal Investigator: John Wentworth, A/Prof

Royal Children's Hospital Melbourne; Recruiting

Parkville, Victoria, Australia, 3052

Contact: Wing Fai Nip +61 (0)3 9345 5208 wingfai.nip@mcri.edu.au

Principal Investigator: Fergus Cameron, Prof

Sponsors and Collaborators

St Vincent's Institute of Medical Research

Juvenile Diabetes Research Foundation

Juvenile Diabetes Research Foundation Australia

Investigators

• Principal Investigator: Tom Kay, Prof; SVI

More Information

Additional Information:

Trial website 

• Responsible Party: St Vincent's Institute of Medical Research
• ClinicalTrials.gov Identifier: NCT04774224
• Other Study ID Numbers: SVI-BARI-01
• First Posted: March 1, 2021
• Last Update Posted: March 1, 2021
• Last Verified: February 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: All of the individual participant data collected during the trial, after de-identification.
• Time Frame: Immediately following publication, and for at least 15 years after the end of the study.

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.

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by St Vincent's Institute of Medical Research:

newly diagnosed

Additional relevant MeSH terms:

Diabetes Mellitus; Diabetes Mellitus, Type 1; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases