Clinical Trials Register

Summary
EudraCT Number:	2022-001713-39
Sponsor's Protocol Code Number:	TCD601F201
National Competent Authority:	Sweden - MPA
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2022-06-02
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Sweden - MPA

A.2

EudraCT number

2022-001713-39

A.3

Full title of the trial

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

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A one year, randomized, placebo-controlled study of TCD601 (siplizumab) in newly diagnosed patients with Type 1 diabetes

A.4.1

Sponsor's protocol code number

TCD601F201

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	ITB-MED AB
B.1.3.4	Country	Sweden
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	ITB-MED AB
B.4.2	Country	Sweden
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	ITB-MED AB
B.5.2	Functional name of contact point	Clinical Trial Information
B.5.3	Address:
B.5.3.1	Street Address	Sonja Kovalevskys Gata 4
B.5.3.2	Town/ city	Stockholm
B.5.3.3	Post code	11366
B.5.3.4	Country	Sweden
B.5.4	Telephone number	8 410 02 887

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Siplizumab
D.3.2	Product code	TCD601
D.3.4	Pharmaceutical form	Solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Siplizumab
D.3.9.1	CAS number	288392-69-8
D.3.9.2	Current sponsor code	TCD601
D.3.9.3	Other descriptive name	Siplizumab
D.3.9.4	EV Substance Code	SUB33504
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	40
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Siplizumab
D.3.2	Product code	TCD601
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Siplizumab
D.3.9.1	CAS number	288392-69-8
D.3.9.3	Other descriptive name	Siplizumab
D.3.9.4	EV Substance Code	SUB33504
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	40
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for infusion
D.8.4	Route of administration of the placebo	Intravenous use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for injection
D.8.4	Route of administration of the placebo	Subcutaneous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

New onset Type I Diabetes

E.1.1.1

Medical condition in easily understood language

New onset Type I Diabetes

E.1.1.2

Therapeutic area

Diseases [C] - Hormonal diseases [C19]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	LLT
E.1.2	Classification code	10045228
E.1.2	Term	Type I diabetes mellitus
E.1.2	System Organ Class	100000004861

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

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.

E.2.2

Secondary objectives of the trial

- Assess the incidence and severity of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) as compared to placebo.

- Quantify clinical and laboratory measures of diabetic disease and glycemic indices of siplizumab compared to placebo.

- Assess the effect of siplizumab on the incidence of local and systemic infections, particularly opportunistic infection.

- Measure PK and PD activity of siplizumab in subjects with T1D.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

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 (See Appendix 3) ≤ 100 days of randomization.
4. Positive for at least one diabetes-related autoantibody against:
o Glutamate decarboxylase (GAD-65),
o Insulin, if obtained prior and up to 10 days of the onset of exogenous insulin therapy,
o Insulinoma antigen-2 (IA-2),
o Zinc transporter-8 (ZnT8), or
o Islet cell autoantibodies against cytoplasmic proteins in the beta cell (ICA).
5. Peak stimulated C-peptide level >0.2 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 ≤ 7.0%.
7. Agreement to use the same CGM model from screening until the end of the study/Week 52 (see Section 9.10.2).
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.

E.4

Principal exclusion criteria

1. Inability or unwillingness to provide written informed consent or comply with the study protocol.
2. History of 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 up to 1 week prior to randomization:
• White blood count (WBC) < 3 x 109/L
• Absolute Lymphocyte Count (ALC) < 800 cells/µL
• Platelet count <150 x 109/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. 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.

E.5 End points

E.5.1

Primary end point(s)

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

E.5.1.1

Timepoint(s) of evaluation of this end point

52 weeks

E.5.2

Secondary end point(s)

• Reported AEs/SAEs and AESIs (e.g., local, and systemic infections) graded per CTCAE criteria.
• Change from baseline in hemoglobin A1c (HbA1c) at weeks 12, 24, 36 and 52.
• The incidence and severity of hypoglycemic episodes over time (AE, blood glucose).
• Change from baseline in exogenous insulin usage at weeks 12, 24, 36 and 52.
• Partial remission as measured by insulin dose adjusted HbA1c (IDAA1c).
• Change in fasting and postprandial blood glucose concentrations by treatment arm at weeks 12, 24, 36 and 52.
• The incidence and severity of ketoacidosis.
• CGM derived Ambulatory Glucose Profiles (AGPs) including mean BG values, Time in Range (TIR), Time Above Range (TAR; High and Very High), Time Below Range (TBR; Low and Very Low) and Glycemic Variability (GV; CV and SD) over time.
• 4h MMTT C-peptide AUC at weeks 12, 24, and 36.
• 4h MMTT C-peptide Peak concentration and percent of subjects with ≥0.2 pmol/mL over the course of the study.
• Incidence, Frequency, and severity of infection AEs/SAEs graded by CTCAE criteria
• Serial measurement of serum siplizumab concentrations.
• Serial measurement of total lymphocyte counts, T-cells subsets over time, and siplizumab dose and serum concentrations.

E.5.2.1

Timepoint(s) of evaluation of this end point

52 weeks

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

Yes

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial months

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

IMP treatment is 12 weeks, Patient will continue to receive standard of care treatment following study end at Week 52. No additional research or treatment is planned following study end.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2022-07-19

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-11-28

P. End of Trial
P.	End of Trial Status	Ongoing

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