A 12-month, randomized, single-blind, placebo-controlled exposure-response study of TCD601 (siplizumab) in new onset type 1 diabetes patients (STRIDE)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Itb-Med AB

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18], Diseases [C] - Hormonal diseases [C19], Diseases [C] - Immune System Diseases [C20]

Trial duration

27 Jan 2023 → 20 Oct 2025

Decision date (initial)

2024-10-23

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

ITB-Med AB

External identifiers

EU CT number

2023-506837-31-00

EudraCT number

2022-001713-39

ClinicalTrials.gov

NCT06025110

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacodynamic, Dose response, Therapy, Efficacy, Pharmacokinetic

The main objective is to determine the effect of 12 weeks of siplizumab treatment on beta-cell function in adults recently diagnosed with T1D compared to placebo at week 52.

Secondary objectives 4

1. Assess the incidence and severity of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) as compared to placebo.
2. Quantify clinical and laboratory measures of diabetic disease and glycemic indices of siplizumab compared to placebo.
3. Assess the effect of siplizumab on the incidence of local and systemic infections, particularly opportunistic infection.
4. Measure PK and PD activity of siplizumab in subjects with T1D.

Conditions and MedDRA coding

New onset type I diabetes

Study design 3 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Able to understand the study requirements and provide written informed consent before any study assessment is performed.
2. Male or female between 18 to 45 years of age.
3. A diagnosis of T1D by a qualified healthcare provider based on ADA guidelines ≤ 100 days of randomization.
4. Positive for at least one diabetes-related autoantibody against: Glutamate decarboxylase (GAD-65), Insulin, if obtained prior and up to 10 days of the onset of exogenous insulin therapy, Insulinoma antigen-2 (IA-2), Zinc transporter-8 (ZnT8), or Islet cell autoantibodies against cytoplasmic proteins in the beta cell (ICA).
5. Peak stimulated C-peptide level >0.2 pmol/mL (200 pmol/L) following a two-hour mixed-meal tolerance test (MMTT) during Screening (Visit 1).
6. Agreement to follow local, regional, or national guidelines for strict glycemic control with targets of HbA1c ≤ 53 mmol/mol (≤ 7.0%).
7. Agreement to use CGM from screening until the end of the study/Week 52
8. Up to date immunization status or agreement to receive routine immunizations according to current country and/or regional guidelines and agree to comply with the guidelines for immunosuppressed individuals and those with chronic disease prior to randomization and receipt of study drug.

Exclusion criteria 18

1. Inability or unwillingness to provide written informed consent or comply with the study protocol.
2. History of and/or suspected intolerance, hypersensitivity, severe reactions, or anaphylaxis to human/humanized monoclonal antibodies or any components of the formulation of siplizumab or its excipients.
3. History of significant allergy (e.g., anaphylaxis) to milk or soy proteins.
4. History of recent [within 3 Months of Screening (Visit 1)] or ongoing serious uncontrolled bacterial, viral, fungal, or other opportunistic infections, including: • Human immunodeficiency virus (HIV) • Current or prior infection with hepatitis B (HBV), as indicated by positive HBsAg or positive HBcAb • Current or prior hepatitis C (HCV), unless treated with anti-viral therapy with achievement of a sustained virologic response (undetectable viral load (VL) 12 weeks after cessation of therapy) • Positive Interferon Gamma Release Assay (IGRA) TB test, e.g., Quantiferon-TB Gold or Quantiferon-TB Gold Plus tests • Active infection with EBV as defined by EBV viral load ≥ 10,000 copies per 106 PBMCs or ≥ 2,000 copies per mL of whole blood • Active infection with Cytomegalovirus (CMV) as defined by CMV viral load ≥ 10,000 IU or copies per mL of whole blood or plasma
5. Any of the following laboratory abnormalities at Screening (Visit 1). Abnormal screening values may be confirmed by a repeat test prior to randomization: • White blood count (WBC) < 3 x 10^9/L • Absolute Lymphocyte Count (ALC) < 800 cells/µL • Platelet count <150 x 10^9/L • Hemoglobin < 100 g/L • ALT ≥ 2x upper limit of normal (ULN) • AST ≥ 2x ULN
6. Current or prior (within 6 months) treatment that is known to alter the natural history of T1D or immunologic status, including high-dose inhaled, extensive topical or systemic glucocorticoids.
7. Active participation in an investigational drug trial within the last six weeks prior to screening.
8. Current or prior (within 14 days of Visit 1 MMTT) use of any medication known to influence glucose tolerance (e.g., atypical antipsychotics, diphenylhydantoin, thiazide, or other potassium-depleting diuretics, β-adrenergic blockers, niacin).
9. Current or prior (within the last 28 days of Visit 1 MMTT) use of metformin, sulfonylureas, glinides, thiazolidinediones, exenatide, liraglutide, DPP-IV inhibitors or amylin.
10. Previous or current diagnosis of malignancy, except adequately treated cervical carcinoma in situ and adequately treated non-metastatic basal and squamous cell carcinoma.
11. History of bone marrow transplantation (BMT) / stem cell transplantation or solid organ transplantation.
12. History or diagnoses of other autoimmune disease, including disease associated with lymphopenia, with the exception of stable thyroid or celiac disease.
13. History of significant cardiovascular disease (including history of myocardial infarction, angina, use of anti-anginal medicines (e.g., nitroglycerin), or abnormal stress test).
14. Vaccination with a live attenuated vaccine (e.g., varicella, measles, mumps, rubella, cold-attenuated intranasal influenza vaccine, bacillus Calmette- Guérin, and smallpox) within 28 days of dosing (Day 0).
15. Past or current medical problems or findings from physical examination or laboratory testing, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant’s ability to comply with study requirements or that may affect the quality or interpretation of the data obtained from the study.
16. Current diagnosed mental illness (e.g., severe depression), current diagnosed or self-reported drug, or alcohol abuse that, in the opinion of the investigator, would interfere with the participant’s ability to comply with study requirements.
17. Women who are pregnant, lactating, or planning on pregnancy during the study.
18. Women of child-bearing potential who are unwilling to use a medically acceptable form of contraception until study Week 52. Contraception is required for 14 days prior to randomization. Highly effective contraception methods include: • Total abstinence (when this is in line with the preferred and usual lifestyle of the subject). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. • Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment. • Male sterilization (at least 6 months prior to screening). For female subjects on the study, the vasectomized male partner should be the sole partner for that subject. • Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example, hormone vaginal ring or transdermal hormone contraception. • Placement of long-acting reversible contraceptives or intrauterine device or intrauterine system. In case of use of oral contraception women should have been stable on the same brand (or generic equivalent) for a minimum of 3 months before taking study treatment. Women are considered post-menopausal and not of childbearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks prior to screening. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of childbearing potential.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from baseline in mean 4 hour stimulated C-Peptide AUC following a MMTT, compared to placebo at week 52.

Secondary endpoints 4

1. Reported AEs/SAEs and AESIs (e.g., local, and systemic infections) graded per CTCAE criteria.
2. • Change from baseline in: hemoglobin A1c (HbA1c); exogenous insulin usage •Incidence and severity of hypoglycemic episodes over time •Partial remission as measured by insulin dose adjusted HbA1c •Change in fasting and postprandial blood glucose concentrations by treatment arm •Incidence and severity of ketoacidosis. •CGM derived Ambulatory Glucose Profiles (AGPs) •4h MMTT C-peptide AUC and 2h MMTT C-peptide AUC •4h MMTT C-peptide peak concentration and percent of subjects with ≥0.2 pmol/mL
3. Incidence, Frequency, and severity of infection AEs/SAEs graded by CTCAE criteria
4. • Serial measurement of serum siplizumab concentrations. • Serial measurement of total lymphocyte counts, T-cells subsets over time, and siplizumab dose and serum concentrations.

Investigational products

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

Test 1

Placebo 1

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Itb-Med AB

Sponsor organisation

Itb-Med AB

Address

Sonja Kovalevskys Gata 4, S:t Matteus S:t Matteus

City

Stockholm

Postcode

113 66

Country

Sweden

Scientific contact point

Organisation

Itb-Med AB

Contact name

Alan Slade

Public contact point

Organisation

Itb-Med AB

Contact name

Clinical Trial Information

Third parties 8

Locations

4 EU/EEA countries · 13 investigational sites

By country

Investigational sites

Country notifications

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 1 · Art. 38 CTR

Corrective measures 1 · Art. 77 CTR

Results and documents

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

Documents 36 files

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

Application history

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