Subcutaneous Administration of Otelixizumab to T1DM Patients

NCT00946257 | Completed Phase 1

• 1 other identifier: 112438
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 6

Brief Summary

This study will assess the subcutaneous administration of otelixizumab to T1DM patients. The study will provide safety, tolerability, pharmacodynamic and pharmacokinetic information which will enable the identification of appropriate safe and well-tolerated subcutaneous dosage regimens to be used in subsequent clinical studies. This study will consist of a screening phase, followed by an in-house phase whereby otelixizumab will be administered to cohorts that will be staggered at each dose level.

Conditions

Diabetes Mellitus, Type 1

Keywords

Type 1 Diabetes Mellitus

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability after a single dose of otelixizumab in T1DM patients

  21 days

Study Arms (6)

Cohort 1

EXPERIMENTAL

0.3 mg dose

Drug: Otelixizumab

Cohort 2

EXPERIMENTAL

0.6 mg dose

Drug: Otelixizumab

Cohort 3

EXPERIMENTAL

1.2 mg dose

Drug: Otelixizumab

Cohort 4

EXPERIMENTAL

1.8 mg dose

Drug: Otelixizumab

Cohort 5

EXPERIMENTAL

2.4 mg dose

Drug: Otelixizumab

Cohort 6

EXPERIMENTAL

3.0 mg dose

Drug: Otelixizumab

Interventions

Otelixizumab DRUG

A humanized, aglycosyl, non-mitogenic, anti CD3 monoclonal antibody (MAb) directed against the ε domain of the human lymphocyte antigen CD3.

Cohort 1; Cohort 2; Cohort 3; Cohort 4; Cohort 5; Cohort 6

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female between 18 and 65 years of age inclusive, at the time of signing the informed consent.
• A female subject is eligible to participate if she is of:
• Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea \[in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) \> 40 mIU/ml and estradiol \< 40 pg/ml (\<140 pmol/L) is confirmatory\]. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods in Section TBC if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method.
• Child-bearing potential and agrees to use one of the contraception methods listed in Section 8.1 to sufficiently minimize the risk of pregnancy. Female subjects must agree to use contraception for at least 2 weeks prior to dosing and for at least 60 days after dosing.
• Male subjects must agree to use one of the contraception methods listed in Section 8.1. This criterion must be followed from the time of the first dose of study medication until 2 weeks after dosing.
• Body weight \> or = 50 kg and BMI within the range 18 - 30 kg/m2 (inclusive).
• Confirmed diagnosis of insulin-requiring T1DM according to the America Diabetes Association criteria and on a relatively stable insulin regimen, with HbAlc \> or = 9%.
• Positive for at least one of the following T1DM-related autoantibodies: anti-GAD (glutamic acid decarboxylase) and/or anti IA 2A.
• Random plasma C-peptide level must be above the level of assay detection at Screen. NOTE: If the screening random plasma C-peptide level is undetectable, subjects must have a Mixed Meal Stimulated C-peptide (MMSCP) equal to or greater than 0.15 nmol/L (0.45 ng/mL) to be eligible for study participation.
• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
• Average QTcB \< 450 msec.
• No history of splenectomy.
• Subject is seropositive for EBV with \< 10,000 copies of EBV DNA per 106 lymphocytes as determined by quantitative polymerase chain reaction.
• CD4+ lymphocyte counts within normal limits within the 30 days before the first dose of study drug.
• Chest X-ray with negative finding at screening

You may not qualify if:

• A positive pre-study drug/alcohol screen. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine, opiates, cannabinoids and benzodiazepines
• Positive for anti Hepatitis C antibody, Hepatitis B surface antigen, and Hepatitis B core antibody at screening
• A positive test for HIV antibody.
• A positive test for syphilis.
• History of regular alcohol consumption within 6 months of the study defined as:
• an average weekly intake of \>21 units for males or \>14 units for females. One unit is equivalent to 8 g of alcohol: a half-pint (\~240 ml) of beer, 1 glass (125 ml) of wine or 1 (25 ml) measure of spirits.
• The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
• Significant and/or active disease in any body system outside of type 1 diabetes mellitus. Examples of significant diseases include but are not limited to: coronary artery disease, congestive heart failure, uncontrolled hypertension, emphysema, seizure disorder.
• Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
• The subject has previously received otelixizumab or any other anti-CD3 Mab (e.g., OKT3, ChAglyCD3, or OKT3 ala ala) or anti-CD20 Mab (e.g. rituximab) at any time.
• Use of prescription or non-prescription drugs, except insulin, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
• History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
• Subjects who have had a prior allergic reaction, including anaphylaxis, to otelixizumab or any other human, humanized, chimeric, or rodent antibodies.
• History of frequent headaches and/or migraine.
• History of atopy.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (6)

GSK Investigational Site

Brussels, 1070, Belgium

Location

GSK Investigational Site

Brussels, 1090, Belgium

Location

GSK Investigational Site

Ghent, 9000, Belgium

Location

GSK Investigational Site

Leuven, 3000, Belgium

Location

GSK Investigational Site

Liège, 4000, Belgium

Location

GSK Investigational Site

Merksem, 2170, Belgium

Location

Related Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.
• Results for study 112438 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

otelixizumab

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 23, 2009
• First Posted: July 24, 2009
• Study Start: July 8, 2009
• Primary Completion: August 1, 2011
• Study Completion: June 25, 2013
• Last Updated: June 1, 2017

Record last verified: 2017-05

Data Sharing

• IPD Sharing: Will share

Locations

BE (6)