IXEKIZUMAB for Type 1 diabetes

Inclusion criteria

• {"criterion_text":"- Signed informed consent and expected cooperation of the patients for the treatment and follow up must be obtained and documented according to ICH GCP, and national/local regulations before trial activities are begun.\n- Must be willing and capable of taking the study drugs and meet for tests and follow up as described.\n- Diagnosed Type 1 Diabetes (E10.9) within 100 days.\n- First injection of insulin maximum 100 days prior to screening. If age 36-45 years, a current insulin regimen of both basal and prandial insulin or alternately use of an insulin pump should exist.\n- Aged 18-45 years old.\n- Presence of antibodies at clinical practice or at screening to at least one of the following antigens: insulin/IAA, GAD-65, IA-2 and ZnT8.\n- Remaining stimulated peak C–peptide ≥ 0.20 nmol/L. If age 36-45 years, peak C-peptide should be <2.0 nmol/L.\n- Male subjects agree to use a reliable method of birth control during the study.\n- Female subjects: Participants of childbearing age or childbearing potential who are sexually active who test negative for pregnancy must be counseled and agree to use either 1 highly effective method of contraception or 2 acceptable methods of contraception combined for the duration of the study and for at least 12 weeks following the last dose of study drug or remain abstinent during the study and for at least 12 weeks following the last dose of study drug. If the highly effective contraceptive methods are contraindicated or strictly declined by patient, acceptable birth control methods may be considered. These may include combination of both of the following methods; Male or female condom with spermicide; Cap, diaphragm, or sponge with spermicide. Highly effective methods of contraception (use 1 form): Combined oral contraceptive pill and mini-pill; NuvaRing®; implantable contraceptives; injectable contraceptives (such as Depo-Provera®); intrauterine device (such as Mirena® and ParaGard®); contraceptive patch—ONLY women <198 pounds or 90 kg; abstinence from sex; vasectomy—for men in clinical studies Effective methods of contraception (use 2 forms combined): male condom with spermicide; female condom with spermicide; diaphragm with spermicide; cervical sponge; cervical cap with spermicide Females who are not of childbearing potential include those who have undergone or who have: female sterilization; hysterectomy; menopause; Müllerian agenesis (Mayer–Rokitansky–Küster–Hauser syndrome [also referred to ascongenital absence of the uterus and vagina])"}

Exclusion criteria

• {"criterion_text":"- Contraindications to Ixekizumab.\n- History of HIV, hepatitis B or C\n- Active or recurrent fungal infection\n- Subjects with myocardial infarction, stroke, unstable angina or heart failure last 6 months Current clinically significant cardiac arrhythmias as verified by ECG\n- Planned surgery during the treatment period of the study (except minor surgery on skin lesions, e.g., nevus)\n- For female subjects: Positive pregnancy test, presently breast-feeding, or unwillingness to use effective contraceptive measures for the duration of the study and 3- months after discontinuation.\n- For male subjects: intent to procreate during the duration of the study or within 3 months after discontinuation or unwillingness of their partner to use effective contraceptive measures for the duration of the study and 4 months after discontinuation.\n- Any history of malignancy the last 5 years except for completely resected squamous or basal cell carcinoma of the skin.\n- Administration of live attenuated vaccine(s) (LAV) within 2 months of enrolment. Or intended use of LAV during the treatment period.\n- The investigator judges that the clinical diagnosis of T1D set is incorrect or uncertain (needs to be confirmed by discussion with experienced diabetologist if excluding due to this criterion)\n- Allergy against ingredients of the investigational products.\n- Treatment with any oral or injected glucose-lowering agents other than insulin.\n- Known allergy or hypersensitivity to any biologic therapy (active substance or excipients) that would pose an unacceptable risk to the patient if participating in the study\n- Presence of serious disease or condition, which in the opinion of the investigator makes the patient non-eligible for the study.\n- Liver injury criteria: patients with active hepatobiliary diseases or at screening having alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2.5 times the upper limit of normal (>2.5 x ULN)\n- Laboratory abnormalities at screening: Neutrophil count < 1,500 cells/ μL (=1,5 *109 cells/ L); Platelet count < 100,000 cells/ μL (= 100 *109 cells/ L); Hemoglobin < 8.5 g/dL (= <85 g/L) (males) and <8g/dL (= <80 g/L) (women)\n- A history of haemolytic anaemia or significantly abnormal haematology/coagulation results at screening.\n- Participation in other clinical trials with a new chemical entity within the previous 3 months.\n- Subjects with severe obesity (BMI >35 kg/m2 if age 18-35 years and BMI >30 kg/m2 if age 36-45).\n- Subjects with other autoimmune disease, e.g. Mb Crohn, Ulcerative colitis, Graves disease, psoriasis, psoriasis arthritis and axial spondylarthrosis, except celiac disease and hypothyroidism which do not need to be excluded for.\n- Active serious or chronic infections (ie: in case patient had a serious infection (eg pneumonia, cellulitis), has been hospitalized, has received intravenous antibiotics for an infection within 12 weeks prior to screening visit, had a serious bone or joint infection within 24 weeks before screening visit, has ever had an infection of an artificial joint\n- Known immunodeficiency or patient is immunocompromised to an extent that participation in the study would pose and unacceptable risk to the patient\n- Tuberculosis"}

Primary endpoints

• {"endpoint_text":"- The primary endpoint is change in residual insulin secretion measured by stimulated C- peptide two-hour area under the curve profile measured by Mixed Meal Tolerance Test (MMTT) between baseline and week 52.","definition_or_measurement_approach":"Change in residual insulin secretion measured by stimulated C-peptide two-hour area under the curve profile measured by Mixed Meal Tolerance Test (MMTT) between baseline and week 52."}

Secondary endpoints

• {"endpoint_text":"- Change in mean Insulin dosage per kilo bodyweight for 24 hours from baseline to week 52.","definition_or_measurement_approach":"Change in mean insulin dosage per kg bodyweight for 24 hours from baseline to week 52."}
• {"endpoint_text":"- Change in time with glucose levels in range (3.9-10 mmol/l) measured by masked CGM (Libre Pro iQ) from baseline to week 52.","definition_or_measurement_approach":"Measured by masked continuous glucose monitoring (Libre Pro iQ); change from baseline to week 52 in time in range (3.9-10 mmol/l)."}
• {"endpoint_text":"- Change in time of hypoglycaemia (<3.9 mmol/l) measured by masked CGM (Libre Pro iQ) from baseline to week 52.","definition_or_measurement_approach":"Measured by masked CGM (Libre Pro iQ); change from baseline to week 52 in time with glucose <3.9 mmol/l."}
• {"endpoint_text":"- Difference in HbA1c from baseline to week 52.","definition_or_measurement_approach":"Change in HbA1c from baseline to week 52."}
• {"endpoint_text":"- Change in time in hypoglycaemia (<3.0 mmol/l) measured by masked CGM (Libre Pro iQ) from baseline to week 52.","definition_or_measurement_approach":"Measured by masked CGM (Libre Pro iQ); change from baseline to week 52 in time with glucose <3.0 mmol/l."}
• {"endpoint_text":"- Change in proinsulin/c-peptide ratio in serum as a measure of beta cell stress from baseline to week 52.","definition_or_measurement_approach":"Change in serum proinsulin/C-peptide ratio from baseline to week 52 as a measure of beta cell stress."}
• {"endpoint_text":"- Change in time in target (3.9-8 mmol/l) measured by masked CGM (Libre Pro iQ) from baseline to week 52.","definition_or_measurement_approach":"Measured by masked CGM (Libre Pro iQ); change from baseline to week 52 in time in target (3.9-8 mmol/l)."}
• {"endpoint_text":"- Change in time in hyperglycaemia >10 mmol/l and ≥ 14 mmol/l measured by masked CGM (Libre Pro iQ) from baseline to week 52.","definition_or_measurement_approach":"Measured by masked CGM (Libre Pro iQ); change from baseline to week 52 in time with glucose >10 mmol/l and ≥14 mmol/l."}
• {"endpoint_text":"- Change in glycaemic variability measured by SD, CV and MAGE by masked CGM (Libre Pro iQ) from baseline to week 52.","definition_or_measurement_approach":"Measured by masked CGM (Libre Pro iQ); change from baseline to week 52 in glycaemic variability metrics (SD, CV, MAGE)."}
• {"endpoint_text":"- Change in proportion of patients with peak residual insulin secretion measured by MMTT: stimulated C-peptide >0.4 pmol/mL from baseline to week 52.","definition_or_measurement_approach":"Proportion of patients with stimulated C-peptide >0.4 pmol/mL measured by Mixed Meal Tolerance Test (MMTT) from baseline to week 52."}
• {"endpoint_text":"- Change in WHO-5 scores from baseline to week 52.","definition_or_measurement_approach":"Change in WHO-5 well-being questionnaire scores from baseline to week 52."}
• {"endpoint_text":"- Change in DTSQs scores from baseline to week 52.","definition_or_measurement_approach":"Change in Diabetes Treatment Satisfaction Questionnaire status (DTSQs) scores from baseline to week 52."}
• {"endpoint_text":"- Change in DTSQc scores estimated at week 52.","definition_or_measurement_approach":"Change in Diabetes Treatment Satisfaction Questionnaire change version (DTSQc) estimated at week 52."}
• {"endpoint_text":"- Change in HCS scores from baseline to week 52.","definition_or_measurement_approach":"Change in Hypoglycaemic Confidence Scale (HCS) scores from baseline to week 52."}
• {"endpoint_text":"- Change in PAID scores from baseline to week 52.","definition_or_measurement_approach":"Change in Problem Areas In Diabetes (PAID) questionnaire scores from baseline to week 52."}
• {"endpoint_text":"- Change in IPAQ scores from baseline to week 52.","definition_or_measurement_approach":"Change in International Physical Activity Questionnaire (IPAQ) scores from baseline to week 52."}
• {"endpoint_text":"- The same variables described above regarding primary, secondary and exploratory endpoints will be evaluated when the variable has been measured at a specific time point from baseline to week 4. baseline to week 13 and baseline to week 26.","definition_or_measurement_approach":"The listed variables will also be evaluated at intermediate time points: baseline to week 4, baseline to week 13 and baseline to week 26."}

Sweden

Earliest CTIS Part Ii Submission Date

24-10-2023

Latest Decision Or Authorization Date

07-01-2025

Processing Time Days

441

Number Of Sites

17

Number Of Participants

127

Primary sponsor

Full Name

University Of Gothenburg

Organisation Type

Educational Institution

Country Of Registered Address

Sweden

Co-sponsors

• NU Hospital Group-Vaestra Goetalandsregionen