ACTIVE_NOT_RECRUITING

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

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

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

Quick Facts

Study Start:2023-10-19

Study Completion:2027-06-30

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:ACTIVE_NOT_RECRUITING

Study ID

NCT05743244

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:12 Years to 35 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT

Inclusion Criteria	Exclusion 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 37 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 37 days of the baseline visit (V0). 10. Participants who are CMV and/or EBV seropositive at screening must be CMV PCR negative and/or EBV PCR \<2,000 IU/mL and must have no signs or symptoms of acute infection at the time of the baseline visit (V0). 11. Be up to date on recommended vaccinations based on age of participants\* 12. 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. 13. 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 14. 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 * For COVID-19 vaccination, all participants will be strongly encouraged to be up-to-date with COVID-19 vaccine (s) as indicated by country-specific guidelines at least 2 weeks prior to the baseline visit (V0). HPV vaccine initiation and/or completion of series may be delayed until after completion of study drug in both adult and pediatric participants.	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 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 had previous clinical use of Tzield (Teplizumab) not part of a T1D treatment study. 27. 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 28. 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 29. ANY of the following conditions at screening: 30. History of chronic alcohol abuse or intravenous drug abuse or other illicit drug abuse within 2 years prior to screening 31. Current or past use of tobacco or nicotine containing products more than the equivalent of 5 cigarettes per day 32. 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 33. Have any complicating medical issues or abnormal clinical laboratory results that may interfere with study conduct, or cause increased risk 34. Any condition that in the investigator's opinion may adversely affect study participation or may compromise the study results

Inclusion Criteria

Exclusion 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 37 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 37 days of the baseline visit (V0).
10. Participants who are CMV and/or EBV seropositive at screening must be CMV PCR negative and/or EBV PCR \<2,000 IU/mL and must have no signs or symptoms of acute infection at the time of the baseline visit (V0).
11. Be up to date on recommended vaccinations based on age of participants\*
12. 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.
13. 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
14. 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
* For COVID-19 vaccination, all participants will be strongly encouraged to be up-to-date with COVID-19 vaccine (s) as indicated by country-specific guidelines at least 2 weeks prior to the baseline visit (V0). HPV vaccine initiation and/or completion of series may be delayed until after completion of study drug in both adult and pediatric participants.

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
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 had previous clinical use of Tzield (Teplizumab) not part of a T1D treatment study.
27. 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
28. 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
29. ANY of the following conditions at screening:
30. History of chronic alcohol abuse or intravenous drug abuse or other illicit drug abuse within 2 years prior to screening
31. Current or past use of tobacco or nicotine containing products more than the equivalent of 5 cigarettes per day
32. 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
33. Have any complicating medical issues or abnormal clinical laboratory results that may interfere with study conduct, or cause increased risk
34. Any condition that in the investigator's opinion may adversely affect study participation or may compromise the study results

Contacts and Locations

Study Locations (Sites)

Children's Hospital Orange County

Orange, California, 92868

United States

Stanford University

Palo Alto, California, 94304

United States

University of California- San Francisco

San Francisco, California, 94143

United States

Barbara Davis Center at University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045

United States

Yale University School of Medicine

New Haven, Connecticut, 06511

United States

University of Florida

Gainesville, Florida, 32610

United States

University of Miami

Miami, Florida, 33136

United States

University of South Florida Diabetes Center

Tampa, Florida, 33612

United States

Emory Children's Center

Atlanta, Georgia, 30322

United States

University of Chicago

Chicago, Illinois, 60637

United States

Indiana University

Indianapolis, Indiana, 46202

United States

University of Louisville Pediatric Endocrinology

Louisville, Kentucky, 40202

United States

Joslin Diabetes Center

Boston, Massachusetts, 02215

United States

University of Minnesota

Minneapolis, Minnesota, 55455

United States

The Children's Mercy Hospital

Kansas City, Missouri, 64111

United States

UBMD Pediatrics

Buffalo, New York, 14203

United States

Columbia University-Naomi Berrie Diabetes Center

New York, New York, 10032

United States

Joslin Center at SUNY Upsate

Syracuse, New York, 13210

United States

University of Pittsburgh

Pittsburgh, Pennsylvania, 15224

United States

Vanderbilt University Medical Center

Nashville, Tennessee, 37232

United States

University of Texas Southwestern

Dallas, Texas, 75390

United States

University of Utah

Salt Lake City, Utah, 84112

United States

Benaroya Research Institute

Seattle, Washington, 98101

United States

Collaborators and Investigators

Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-10-19

Study Completion Date2027-06-30

Study Record Updates

Study Start Date2023-10-19

Study Completion Date2027-06-30

Terms related to this study

Keywords Provided by Researchers

TrialNet
T1D

Additional Relevant MeSH Terms

Diabetes Mellitus, Type 1