Baricitinib in New-onset Type 1 Diabetes

NCT04774224 | Completed Phase 2 DMC

• 1 other identifier: SVI-BARI-01
• Study Type: interventional
• Target: 91
• Locations: 1 country
• Sites: 4

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 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.

Conditions

Type 1 Diabetes

Keywords

newly diagnosed

Outcome Measures

Primary Outcomes (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.

  Measured at 48 weeks post commencement of intervention.

Secondary Outcomes (7)

• 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.

Study Arms (2)

Baricitinib

ACTIVE COMPARATOR

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

Placebo

PLACEBO COMPARATOR

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

Interventions

Baricitinib DRUG

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.

Baricitinib

Placebo DRUG

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.

Placebo

Eligibility Criteria

• Age: 10 Years - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Male or female aged between 10 and 30 years (inclusive) at screening;
• Diagnosis of T1D according to ADA criteria within 100 days prior to starting study drug;
• Islet autoantibody positivity (one or more of: GADA, IA-2A, IAA (assessed within one week of commencing insulin therapy), ZnT8A);
• 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.
• Participants of childbearing age who are sexually active must agree to use of effective birth control until the end of the study;
• Be able to read, understand and give written informed consent;
• Be willing to comply with intensive diabetes management.

You may not qualify if:

• Use of immunosuppressive or immunomodulatory therapies other than inhaled or topical glucocorticoids;
• Current or past history of deep vein thrombosis or pulmonary embolism;
• Impaired renal function defined by estimated glomerular filtration rate (according to the CKD-EPI) of \< 60 mL/min/1.73 m2;
• LDL cholesterol \>4mmol/l;
• Elevated liver function tests at screening:
• Aspartate aminotransferase 2x ULN
• Alanine aminotransferase 2 x ULN;
• Clinically significant abnormal laboratory parameters at screening including but not limited to:
• Hemoglobin \< 8 g/L;
• White blood cells \<2500 cells/µl;
• Lymphocyte count \<750 cells/µl;
• Platelets \<50,000 cells/µl;
• Neutrophils \<1200cells/µL;
• Known hypersensitivity to baricitinib;
• Known malignancy with the exception of successfully treated non- metastatic basal cell and squamous cell carcinoma;

Sponsors & Collaborators

• St Vincent's Institute of Medical Research: lead
• Juvenile Diabetes Research Foundation Australia: collaborator
• Juvenile Diabetes Research Foundation: collaborator

Study Sites (4)

Women's and Children's Hospital Adelaide

North Adelaide, South Australia, 5006, Australia

Location

St Vincent's Hospital Melbourne

Fitzroy, Victoria, 3065, Australia

Location

Royal Melbourne Hospital

Parkville, Victoria, 3050, Australia

Location

Royal Children's Hospital Melbourne

Parkville, Victoria, 3052, Australia

Location

Related Publications (2)

• 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.

  PMID: 35606820 BACKGROUND

• Waibel M, Wentworth JM, So M, Couper JJ, Cameron FJ, MacIsaac RJ, Atlas G, Gorelik A, Litwak S, Sanz-Villanueva L, Trivedi P, Ahmed S, Martin FJ, Doyle ME, Harbison JE, Hall C, Krishnamurthy B, Colman PG, Harrison LC, Thomas HE, Kay TWH; BANDIT Study Group. Baricitinib and beta-Cell Function in Patients with New-Onset Type 1 Diabetes. N Engl J Med. 2023 Dec 7;389(23):2140-2150. doi: 10.1056/NEJMoa2306691.

  PMID: 38055252 RESULT

Related Links

• Trial website

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

baricitinib

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Tom Kay, Prof

  SVI

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomised placebo controlled trial

Study Record Dates

• First Submitted: February 22, 2021
• First Posted: March 1, 2021
• Study Start: October 30, 2020
• Primary Completion: January 30, 2023
• Study Completion: May 6, 2024
• Last Updated: December 3, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share
• 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.

Locations

AU (4)