Janus Kinase (JAK) Inhibitors to Preserve C-Peptide Production in New Onset Type 1 Diabetes (T1D)
Study Details
Study Description
Brief 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed 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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Abrocitinib Abrocitinib will be self-administered as 200-milligram (mg) tablet daily for 52 weeks (12 months). The final prepared product is to be labeled to protect the blind. |
Drug: Abrocitinib 200 MG Oral Tablet
Abrocitinib
Other Names:
|
| Experimental: Ritlecitinib Ritlecitnib will be self-administered via oral administration as a 100-mg capsule daily for 52 weeks (12 months). The final prepared product is to be labeled to protect the blind. |
Drug: Ritlecitinib
Ritlecitinib
|
| Placebo Comparator: Placebo 200 mg tablet or 100 mg capsule matching either abrocitinib or ritlecitinib will be self-administered via oral administration daily for 52 weeks (12 months). The final product is to be labeled to protect the blind. |
Drug: Placebo
Placebo for Abrocitinib or Ritlecitinib
|
Outcome Measures
Primary Outcome Measures
- The area under the stimulated C-peptide curve (Y_AUC) [12 Months]
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.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Provide informed consent or assent as appropriate and, if < 18 years of age have a parent or legal guardian provide informed consent
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Age 12-35 years (both inclusive) at the time of signing informed consent and assent
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Diagnosis of T1D within 100 days of randomization.
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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
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Stimulated C-peptide of ≥0.2 pmol/mL measured during mixed-meal tolerance test (MMTT) conducted at least 21 days from diagnosis of diabetes
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HbA1c ≤ 10 %
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Body weight ≥ 35kg at screening
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Willing to comply with intensive diabetes management and wear a Continuous Glucose Monitoring Device (CGM)
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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 randomization
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Be up to date on recommended immunizations; participants are required to receive killed influenza vaccination at least 2 weeks prior to randomization 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.
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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 randomization
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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
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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:
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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
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Untreated hypothyroidism or active Graves' disease
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Concurrent treatment with other immunosuppressive agents (including biologics or steroids), other than inhaled or topical glucocorticoids
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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
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Active acute or chronic infection requiring treatment with intravenous therapy (IV) within a minimum 1 month prior to Day 0
- Specific cases should be reviewed by Infectious Disease Committee prior to enrollment
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Significant trauma or major surgery within 1 month of signing informed consent.
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Considered in imminent need for surgery or with elective surgery scheduled to occur during the study
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History of disseminated herpes zoster or disseminated herpes simplex or a recurrent (more than one episode of) localized, dermatomal herpes zoster
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Have evidence of prior or current tuberculosis infection as assessed by Purified Protein Derivative (PPD), interferon gamma release assay (IGRA) or by history
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Have evidence of current or past HIV or Hepatitis B infection
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Have evidence of active Hepatitis C infection
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Have current, confirmed COVID-19 infection
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Current or history of Deep vein thrombosis (DVT), Pulmonary embolism (PE), or other thromboembolic events or history of inherited coagulopathies
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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
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Any present malignancies or history of malignancy, other than a successfully treated nonmelanoma skin cancer
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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
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One or more screening laboratory values as stated
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Neutrophils < 1,500 /μL
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Lymphocytes < 800 /μL
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Platelets < 150,000 / μL
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Hemoglobin < 6.2 mmol/L (10.0 g/dL)
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Potassium > 5.5 mmol/L or <3.0 mmol/L
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Sodium > 150mmol/L or < 130mmol/L
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AST or ALT ≥ 2.5 times the upper limit of normal
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Bilirubin ≥ 1.5 times upper limit of normal unless diagnosed with Gilbert's syndrome
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LDL >160 mg/dL
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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)
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Be currently pregnant or lactating or anticipate becoming pregnant during the study
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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
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Be currently participating in another T1D treatment study
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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
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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
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ANY of the following conditions at screening:
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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).
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Long QT Syndrome, a family history of Long QT Syndrome, or a history of Torsades de Pointes (TdP).
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History of chronic alcohol abuse or intravenous drug abuse or other illicit drug abuse within 2 years prior to screening
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Current or past use of tobacco or nicotine containing products more than the equivalent of 5 cigarettes per day
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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
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Have any complicating medical issues or abnormal clinical laboratory results that may interfere with study conduct, or cause increased risk
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Any condition that in the investigator's opinion may adversely affect study participation or may compromise the study results
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Pfizer
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- TN31 JAK Inhibitors