Ixekizumab Diabetes Intervention Trial (I-DIT)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

University Of Gothenburg, NU Hospital Group-Vaestra Goetalandsregionen

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hormonal diseases [C19]

Trial duration

25 Oct 2022 → ongoing

Decision date (initial)

2024-10-25

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2023-508588-58-00

EudraCT number

2019-001188-58

ClinicalTrials.gov

NCT04589325

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

The primary objective of the study is to examine whether Ixekizumab compared with placebo increases residual insulin secretion measured by stimulated C-peptide two-hour area under the curve profile (Mixed Meal Tolerance Test) in newly diagnosed patients with type 1 diabetes.

Secondary objectives 15

1. Change in Mean Insulin dosage per kilo body weight
2. Change in Time in range (3.9-10 mmol/l) measured by masked CGM
3. Change in Time in hypoglycaemia (<3.9 mmol/l) measured by masked CGM
4. Change in Difference in HbA1c
5. Change in Time in hypoglycaemia (<3.0 mmol/l) measured by masked CGM
6. Change in Proinsulin/c-peptide ratio in serum as a measure of beta cell stress
7. Change in Time in glucose target (3.9-8 mmol/l) measured by masked CGM
8. Change in Time in hyperglycaemia >10 mmol/l and ≥14 mmol/l measured by masked CGM
9. Change in Glycaemic variability SD, CV and MAGE
10. Change in Proportion of patients with peak residual insulin secretion measured by Mixed Meal Tolerance Test (MMTT): stimulated C-peptide >0.4 pmol/mL
11. Change in Well-being measured using the World Health Organization-5 (WHO-5) questionnaire
12. Change in Treatment satisfaction measured using the Diabetes Treatment satisfaction Questionnaire (DTSQ)
13. Change in Hypoglycaemic confidence measured using the Hypoglycaemic Confidence Scale
14. Change in Diabetes-related distress measured using the Problem Areas in Diabetes Scale (PAID
15. Change in Physical activity measured using the International Physical Activity Questionnaire (IPAQ)

Conditions and MedDRA coding

Diabetes type 1

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. 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.
2. Must be willing and capable of taking the study drugs and meet for tests and follow up as described.
3. Diagnosed Type 1 Diabetes (E10.9) within 100 days.
4. 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.
5. Aged 18-45 years old.
6. 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.
7. Remaining stimulated peak C–peptide ≥ 0.20 nmol/L. If age 36-45 years, peak C-peptide should be <2.0 nmol/L.
8. Male subjects agree to use a reliable method of birth control during the study.
9. 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 23

1. Contraindications to Ixekizumab.
2. Treatment with any oral or injected glucose-lowering agents other than insulin.
3. A history of haemolytic anaemia or significantly abnormal haematology/coagulation results at screening.
4. Participation in other clinical trials with a new chemical entity within the previous 3 months.
5. Subjects with severe obesity (BMI >35 kg/m2 if age 18-35 years and BMI >30 kg/m2 if age 36-45).
6. 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.
7. 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
8. Known immunodeficiency or patient is immunocompromised to an extent that participation in the study would pose and unacceptable risk to the patient
9. Tuberculosis
10. History of HIV, hepatitis B or C
11. Active or recurrent fungal infection
12. Subjects with myocardial infarction, stroke, unstable angina or heart failure last 6 months Current clinically significant cardiac arrhythmias as verified by ECG
13. Planned surgery during the treatment period of the study (except minor surgery on skin lesions, e.g., nevus)
14. 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.
15. 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.
16. Any history of malignancy the last 5 years except for completely resected squamous or basal cell carcinoma of the skin.
17. Administration of live attenuated vaccine(s) (LAV) within 2 months of enrolment. Or intended use of LAV during the treatment period.
18. 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)
19. Allergy against ingredients of the investigational products.
20. 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
21. Presence of serious disease or condition, which in the opinion of the investigator makes the patient non-eligible for the study.
22. 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)
23. 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)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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.

Secondary endpoints 17

1. Change in mean Insulin dosage per kilo bodyweight for 24 hours from baseline to week 52.
2. 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.
3. Change in time of hypoglycaemia (<3.9 mmol/l) measured by masked CGM (Libre Pro iQ) from baseline to week 52.
4. Difference in HbA1c from baseline to week 52.
5. Change in time in hypoglycaemia (<3.0 mmol/l) measured by masked CGM (Libre Pro iQ) from baseline to week 52.
6. Change in proinsulin/c-peptide ratio in serum as a measure of beta cell stress from baseline to week 52.
7. Change in time in target (3.9-8 mmol/l) measured by masked CGM (Libre Pro iQ) from baseline to week 52.
8. Change in time in hyperglycaemia >10 mmol/l and ≥ 14 mmol/l measured by masked CGM (Libre Pro iQ) from baseline to week 52.
9. Change in glycaemic variability measured by SD, CV and MAGE by masked CGM (Libre Pro iQ) from baseline to week 52.
10. 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.
11. Change in WHO-5 scores from baseline to week 52.
12. Change in DTSQs scores from baseline to week 52.
13. Change in DTSQc scores estimated at week 52.
14. Change in HCS scores from baseline to week 52.
15. Change in PAID scores from baseline to week 52.
16. Change in IPAQ scores from baseline to week 52.
17. 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.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

University Of Gothenburg

Sponsor organisation

University Of Gothenburg

Address

P. O. Box 100

City

Gothenburg

Postcode

405 30

Country

Sweden

Scientific contact point

Organisation

University Of Gothenburg

Contact name

Marcus Lind

Public contact point

Organisation

University Of Gothenburg

Contact name

Marcus Lind

NU Hospital Group-Vaestra Goetalandsregionen

Sponsor organisation

NU Hospital Group-Vaestra Goetalandsregionen

Address

Larketorpsvagen

City

Trollhattan

Postcode

461 85

Country

Sweden

Sponsor responsibilities

Article 77 compliance

University Of Gothenburg

Contact point sponsor

University Of Gothenburg

Article 77 implementation

University Of Gothenburg

Locations

1 EU/EEA country · 17 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 4 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications