Janus Kinase (JAK) Inhibitors to Preserve C-Peptide Production in New Onset Type 1 Diabetes (T1D)

Diabetes Mellitus, Type 1 Clinical Trial

Official title:

A Phase 2 Multi-Center, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Subtype-Selective JAK Inhibitors for Preservation of Pancreatic β Cell Function in Newly Diagnosed Type 1 Diabetes Mellitus

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05743244
• Other study ID #: TN31 JAK Inhibitors
• Status: Recruiting
• Phase: Phase 2
• Start date: October 19, 2023
• Est. completion date: June 30, 2027

Study information

• Verified date: October 2023
• Source: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Contact: Jessica S Conaty
• Phone: 8133969234
• Email: Jessica.Conaty[@]epi.usf.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A multi-center, placebo-controlled, double blind, 1:1:1 randomized control clinical trial testing two different JAK Inhibitors abrocitnib, ritlecitinib, and placebo in subjects with recent onset Stage 3 Type 1 Diabetes within 100 days of diagnosis.

Description:

This study has a total sample size of 78 participants. Of that 78, 52 participants will receive active treatment, and a total of 26 participants will receive placebo. Participants will receive 12 months of active treatment with abrocitinib, ritlecitinib, or placebo with up to 12 months of additional follow-up. During the study, participants will undergo frequent assessments of their insulin production, immunologic status, overall health and well-being and diabetes care.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 78
• Est. completion date: June 30, 2027
• Est. primary completion date: June 30, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 35 Years

Eligibility

Inclusion Criteria:

1. Provide informed consent or assent as appropriate and, if < 18 years of age have a parent or legal guardian provide informed consent

2. Age 12-35 years (both inclusive) at the time of signing informed consent and assent

3. Diagnosis of T1D within 100 days of the baseline visit (V0).

4. Positive for at least one islet cell autoantibody; Glutamate decarboxylase (GAD)65A, mIAA (if obtained within 10 days of the onset of insulin therapy), IA-2A, ICA, or ZnT8A

5. Stimulated C-peptide of =0.2 pmol/mL measured during mixed-meal tolerance test (MMTT) conducted at least 21 days from diagnosis of diabetes

6. HbA1c = 10 %

7. Body weight = 35kg at screening

8. Willing to comply with intensive diabetes management and wear a Continuous Glucose Monitoring Device (CGM)

9. Participants who are Cytomegalovirus (CMV) and/or Epstein-Barr virus (EBV) seronegative at screening must be CMV and/or EBV Polymerase chain reaction (PCR) negative within 30 days of randomization and may not have had signs or symptoms of a CMV and/or EBV-compatible illness lasting longer than 7 days within 30 days of the baseline visit (V0).

10. Be up to date on recommended immunizations; participants are required to receive killed influenza vaccination at least 2 weeks prior to the baseline visit (V0) when vaccine for the current or upcoming flu season is available. Enrollment must be delayed at least 4 weeks from administration of a killed vaccine other than influenza and 6 weeks from a live vaccination. Vaccinations should not be given while on study drug and be postponed at least 3 months after the last dose of study drug.

11. Participants are required to be fully vaccinated including eligible boosters and should receive an authorized non-live COVID-19 vaccination series or COVID-19 vaccine at least 2 weeks prior to the baseline visit (V0).

12. If participant is female with reproductive potential, she must have a negative pregnancy test at screening and be willing to avoid pregnancy using a highly-effective contraceptive method for the duration of the study

13. Males of reproductive age must use a highly-effective contraceptive method during the treatment phase and for 3 months following last dose of study drug

Exclusion Criteria:

1. Current or ongoing use of non-insulin pharmaceuticals or medication that affect glycemic control or glucose homeostasis within 7 days prior to screening or any prohibited concomitant medication listed in section 4.8

2. Untreated hypothyroidism or active Graves' disease

3. Concurrent treatment with other immunosuppressive agents (including biologics or steroids), other than inhaled or topical glucocorticoids

4. Active acute or chronic infection requiring treatment with oral antibiotics, antivirals, antiparasitics, antiprotozoals, or antifungals within 1 month prior to Day 0 or superficial skin infection within 1 week prior to Day 0

5. Active acute or chronic infection requiring treatment with intravenous therapy (IV) within a minimum 1 month prior to Day 0

a. Specific cases should be reviewed by Infectious Disease Committee prior to enrollment

6. Have active signs or symptoms of acute infection at the time of the baseline visit (V0).

7. Significant trauma or major surgery within 1 month of signing informed consent.

8. Considered in imminent need for surgery or with elective surgery scheduled to occur during the study

9. History of disseminated herpes zoster or disseminated herpes simplex or a recurrent (more than one episode of) localized, dermatomal herpes zoster

10. Have evidence of prior or current tuberculosis infection as assessed by Purified Protein Derivative (PPD), interferon gamma release assay (IGRA) or by history

11. Have evidence of current or past HIV or Hepatitis B infection

12. Have evidence of active Hepatitis C infection

13. Have current, confirmed COVID-19 infection

14. Current or history of Deep vein thrombosis (DVT), Pulmonary embolism (PE), or other thromboembolic events or history of inherited coagulopathies

15. First degree relative with a history of unprovoked venous thromboembolism (i.e. without known underlying cause such as trauma, surgery, immobilization, prolonged travel, pregnancy, hormone use, or plaster cast), which suggests that a participant may be at increased risk of inherited coagulation disorder

16. Any present malignancies or history of malignancy, other than a successfully treated nonmelanoma skin cancer

17. History of any lymphoproliferative disorder such as EBV-related lymphoproliferative disorder, history of lymphoma, history of leukemia, or signs and symptoms suggestive of current lymphatic or lymphoid disease

18. Known or suspected polymorphism in the Cytochrome P450 2C19 (CYP2C19 gene, resulting in classification as a poor CYP2C19 metabolizer).

19. Have renal impairment (eGFR< 60 mL/min)

20. Currently on anti-platelet therapies, excluding low dose aspirin

21. One or more screening laboratory values as stated

1. Neutrophils < 1,500 /µL

2. Lymphocytes < 800 /µL

3. Platelets < 150,000 / µL

4. Hemoglobin < 6.2 mmol/L (10.0 g/dL)

5. Potassium > 5.5 mmol/L or <3.0 mmol/L

6. Sodium > 150mmol/L or < 130mmol/L

7. AST or ALT = 2.5 times the upper limit of normal

8. Bilirubin = 1.5 times upper limit of normal unless diagnosed with Gilbert's syndrome

9. LDL >160 mg/dL

22. Vaccination with a live virus within the last 6 weeks and killed vaccine within 4 weeks (except 2 weeks for flu vaccine and COVID vaccine)

23. Be currently pregnant or lactating or anticipate becoming pregnant during the study

24. Male participants able to father children and female participants of childbearing potential who are unwilling or unable to use 2 effective methods (at least 1 highly effective method) of contraception, including abstinence, as outlined in this protocol for the duration of the study and for at least 3 months after the last dose of investigational product

25. Be currently participating in another T1D treatment study

26. Have hearing loss with progression over the previous 5 years, or sudden hearing loss, or middle or inner ear disease such as otitis media, cholesteatoma, Meniere's disease, labyrinthitis, or other auditory condition that is considered acute, fluctuating, or progressive

27. Acute coronary syndrome (e.g., myocardial infarction, unstable angina pectoris) and any history of cerebrovascular disease within 24 weeks before screening; Heart failure NYHA (New York Heart Association) III, NYHA IV

28. ANY of the following conditions at screening:

a. Screening 12-lead electrocardiogram (ECG) that demonstrates: i. Clinically significant abnormalities requiring treatment (eg, acute myocardial infarction, serious tachy- or brady-arrhythmias) or indicating serious underlying heart disease (eg, cardiomyopathy, Wolff-Parkinson- White syndrome); ii. Confirmed QT corrected using Fridericia's correction factor (QTcF) prolongation (>450 milliseconds).

b. Long QT Syndrome, a family history of Long QT Syndrome, or a history of Torsades de Pointes (TdP).

29. History of chronic alcohol abuse or intravenous drug abuse or other illicit drug abuse within 2 years prior to screening

30. Current or past use of tobacco or nicotine containing products more than the equivalent of 5 cigarettes per day

31. Participant is the investigator or any sub-investigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the trial

32. Have any complicating medical issues or abnormal clinical laboratory results that may interfere with study conduct, or cause increased risk

33. Any condition that in the investigator's opinion may adversely affect study participation or may compromise the study results

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1

Intervention

Drug:
• Abrocitinib 200 MG Oral Tablet
Abrocitinib
• Ritlecitinib
Ritlecitinib
• Placebo
Placebo for Abrocitinib or Ritlecitinib

Locations

Country	Name	City	State
United States	Emory Children's Center	Atlanta	Georgia
United States	Barbara Davis Center at University of Colorado Anschutz Medical Campus	Aurora	Colorado
United States	University of Texas Southwestern	Dallas	Texas
United States	University of Florida	Gainesville	Florida
United States	Indiana University	Indianapolis	Indiana
United States	The Children's Mercy Hospital	Kansas City	Missouri
United States	University of Minnesota	Minneapolis	Minnesota
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Yale University School of Medicine	New Haven	Connecticut
United States	Columbia University-Naomi Berrie Diabetes Center	New York	New York
United States	Children's Hospital Orange County	Orange	California
United States	Stanford University	Palo Alto	California
United States	University of Pittsburgh	Pittsburgh	Pennsylvania
United States	University of California- San Francisco	San Francisco	California
United States	Benaroya Research Institute	Seattle	Washington
United States	University of South Florida Diabetes Center	Tampa	Florida

Sponsors (2)

Lead Sponsor	Collaborator
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)	Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The area under the stimulated C-peptide curve (Y_AUC)	The primary outcome of interest is the area under the stimulated C-peptide curve over the 2-hour mixed meal glucose tolerance test conducted at the 12-month visit (Y_AUC) over the 2-hour mixed meal glucose tolerance test conducted at the 12-month visit.	12 Months

External Links

•   TrialNet