Itolizumab (T1h) combined with insulin in patients with Type I Diabetes Mellitus

General information

Section to complete general information about the trial: scientific and public title, protocol identifiers, sponsors and Source(s) of Monetary or Material Support.

Scientific title:

Evaluation of the safety and therapeutic effect of the humanized anti-CD6 monoclonal antibody itolizumab (T1h) combined with insulin in the treatment of patients with type 1 diabetes mellitus

Secondary indentifying numbers:

IIC RD-EC 149

Issuing authority of the secondary identifying numbers:

Center of Molecular Immunology (CIM)

Source(s) of monetary or material support:

Center of Molecular Immunology (CIM) Ministry of Public Health (MINSAP)

Authorization for beginning

Section to complete information about the regulatory approval of clinical trial: regulatory agency name, approval date and reference number in the agency.

Regulatory instance to authorize the initiation of the study:

Center for State Control of Drugs, Medical Devices and Equipment (CECMED)

Authorization date :

25/11/2013

Reference number:

05.003.13.B

Principal investigator

Section to complete information about Email address, telephone number and postal address of the Principal Investigator.

First name:

Eduardo

Last name:

Cabrera Rode

Medical Specialty :

PhD in Biological Sciences

Affiliation:

National Institute of Endocrinology and Metabolic Diseases

Postal address:

Zapata and D, Vedado

City:

Havana

Country:

Cuba

Zip Code:

10400

Telephone:

+53-78329707

Email address:

diabetes@infomed.sld.cu

Clinical sites to participate

Section to complete the data related to the clinical sites involved in the trial: site and responsible investigator for every site.

Countries of recruitment:

Cuba

Clinical sites:

Not applicable

Research ethics committees:

National Institute of Endocrinology and Metabolic Diseases, December 21, 2012

Recruitment status

Section to complete information about the recruitment status and the date of first enrolment subject

Recruitment status:

Recruiting

Date of first enrollment:

06/10/2014

Health condition and Intervention

Section to complete information about the primary medical condition(s) or problem(s) studied and, a characteristics of the intervention(s).

Health condition(s) or Problem(s) studied:

Type 1 diabetes mellitus

Health condition(s) code:

Diabetes Mellitus, Type 1

Diabetes Mellitus

Glucose Metabolism Disorders

Metabolic Diseases

Nutritional and Metabolic Diseases

Endocrine System Diseases

Autoimmune Diseases

Immune System Diseases

Intervention(s):

The study will cover 52 weeks and consist of two consecutive stages. The first stage (week 0 to week 24) will include treatment with T1h or placebo combined with insulin and will last 24 weeks. The second stage (week 25 to week 52) will comprise only the insulin treatment with monitoring the evolution of the disease and will last 28 weeks. Group 1 (Experimental): Itolizumab (T1h) 0.4 mg/kg by intravenous route (IV), every week for 2 months and then every 4 weeks until completing 6 months. Group 2 (Experimental): Itolizumab (T1h) 0.8 mg/kg by intravenous route (IV), every week for 2 months and then every 4 weeks until completing 6 months. Group 3 (Experimental): Itolizumab (T1h) 1.6 mg/kg by intravenous route (IV), every week for 2 months and then every 4 weeks until completing 6 months. Group 4 (Control): Placebo every week for 2 months and then every 4 weeks until completing 6 months. All groups receive concomitant insulin on an intensive care regimen by intravenous route (IV) (infusion, two hours, in 200 mL of sterile sodium chloride solution)

Intervention code:

Antibodies, Monoclonal, Humanized

Insulin

Antibodies, Monoclonal

Administration, Intravenous

Placebos

Intervention keyword:

Itolizumab, T1h, anti-CD6

Outcomes and Timepoint

Section to complete information about primary and secondary outcomes including. It includes the metric or method of measurement used and, the time point for every outcome.

Primary outcome(s):

Safety outcomes: Incidence of Adverse Events (AE) (type (name of AE), Intensity (Mild, Moderate, Severe), Gravity (Serious, Not serious), causality relationship (Very Likely, Likely, Possible, Not related, Unknown). Measuring time: 52 weeks.

Key secondary outcomes:

Efficacy outcomes: -Area under the curve (AUC) of stimulated C-peptide production. Measurement Time: Initial Evaluation, Weeks 25, 36 and 52 -Peak of stimulated C-peptide production. Measurement Time: Initial Evaluation, Weeks 25, 36 and 52 -Non-stimulated C-peptide. Measurement Time: Initial Evaluation, Weeks 25, 36 and 52 -Glycosylated hemoglobin, HbA1c (%). Measurement Time: Initial Evaluation, Weeks 25, 36 and 52 -Doses of basal, prandial and total daily insulin (IU, IU / kg). Measuring time: 52 weeks. -Fasting and postprandial glycemia based on laboratory blood chemistry. Measurement time: initial evaluation, before receiving 5th administration, one week after administration 9, one week after administration 13 and during follow-up at weeks 36, 44 and 52 -Glucose by self-monitoring (glucometer). Measuring time: 52 weeks.

Selection criterias

Section to complete information about the inclusion and exclusion criteria for participant selection, including age and gender.

Gender:

Male/Female

Minimum age:

18 years

Maximum age:

35 years

Inclusion criteria:

1. Patient with a diagnosis of DM1 of not more than 12 weeks. 2. Patient under intensive treatment with insulin in stable dose, for at least 4 weeks before inclusion. 3. Patient aged 18-35 years (both included), of any sex or skin color. 4. Patient with stimulated C-peptide levels (MMTT) ≥0.2 pmol / ml, at not more than 8 weeks prior to inclusion. 5. Patient with clinical laboratory values: Hemogram: Hemoglobin-man ≥ 12.0 g / dl, -women ≥ 11.0 g / dl; Leukocytes> 4.5x109 cel / mL, Neutrophils> 1.8 x 109 / L, Lymphocytes> 1.2x109 cel / mL, Platelets> 150x109 / mL; Hepatic function: Transaminases within the normal reference values established in the institution (TGP <49 U / l and TGO <46 U / l); Γ-glutamyltransferase (GGT), men ≤ 65 U / l, female ≤ 45 U / l), Renal function: Creatinine <128 μmol / L 6. Patient who expressed in written form in their informed consent form their willingness to participate in the clinical trial.

Exclusion criteria:

1. Patient with severe malnutrition. 2. Patient with a history of severe chronic diseases of the Central Nervous System, Respiratory System, Cardiovascular Apparatus, Gastrointestinal Tract, or Genitourinary System. 3. Patient with a history of malignant neoplasia. 4. Patient suffering from acquired or congenital diseases of the hemolympho- opetic system. 5. Patient with clinically detected acute or chronic infection (laboratory tests and chest X-rays, including HIV infection, Hepatitis B and C, Epstein Bar and Cytomegalovirus). 6. Patient suffering from bronchial asthma, atopic dermatitis or chronic urticaria. 7. Patient receiving hyperglycemic drugs (beta-blockers, ACE inhibitors, Nicotinic Acid, Interferon). 8. Patient with ongoing treatment or in the last six months with high doses of steroids or other immunosuppressive agents (imuran, azatriopine, methotrexate, cyclophosphamide, cyclosporin A, tacrolimus, mycophenolate-mofetil, immunoglobulin ev [> 400 mg / kg]) . 9. Pregnancy, puerperium and / or breastfeeding. 10. Patient woman and man with reproductive capacity who refuse to avoid conception during the study. 11. Patient with a history of alcoholism or drug addiction. 12. Patient with history of allergy attributed to compounds of chemical or biological composition similar to the monoclonal antibody T1h. 13. Patient with intellectual or sensory psychological dysfunction that may impede the understanding and fulfillment of study requirements according to the Principal Investigator's criteria.

Type of population:

Adults

Type of participant:

Patients

Study design

Section to complete information about the characteristics of the study design.

Type study:

Interventional

Purpose:

Treatment

Allocation:

Randomized controlled trial

Masking:

Double Blind

Control group:

Placebo

Study design:

Parallel

Phase:

1-2

Target sample size:

40

Contact for public queries

Section to complete information about Email address, telephone number and postal address of the contact who will respond to general queries, including information about current recruitment status

First Name:

Patricia

Last Name:

Hernandez Casanna

Specialty:

PhD, Research Promoter

Affiliation:

Center of Molecular Immunology (CIM)

Postal Address:

216th & 15th Ave., Atabey, Playa

City:

Havana

Country:

Cuba

Zip Code:

11600

Telephone:

+537-2717933

Email :

patriciahc@cim.sld.cu

Contact for scientific queries

Section to complete information about Email address, telephone number and postal address of the contact who will respond to scientific queries.

First Name:

Patricia

Last Name:

Hernandez Casanna

Specialty:

PhD, Research Promoter

Affiliation:

Center of Molecular Immunology (CIM)

Postal Address:

216th & 15th Ave., Atabey, Playa

City:

Havana

Country:

Cuba

Zip Code:

11600

Telephone:

+537-2717933

Email :

patriciahc@cim.sld.cu

Registration and Update

Section to complete information about the name of Primary Registry, date of registration and the unique ID number assigned by the registry (RPCEC).

Primary registry:

RPCEC

Unique ID number:

RPCEC00000225

Date of Registration in Primary Registry:

23/12/2016

Record Verification Date:

2016/12/23

Next update date:

2017/12/23

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Itolizumab (T1h) combined with insulin in patients with Type I Diabetes Mellitus

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