Overview

A Safety and Tolerability Study of Otelixizumab in Thyroid Eye Disease

Status:
Terminated
Trial end date:
2012-08-29
Target enrollment:
0
Participant gender:
All
Summary
The purpose of this study is to investigate the safety and tolerability of otelixizumab in patients with Graves' ophthalmopathy (thyroid eye disease). There is currently no alternative therapy available for this condition other than treatment with steroids, or radiotherapy and surgery. The study also includes a comparison of the current steroid treatment, methylprednisolone, with the proposed new otelixizumab treatment.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
GlaxoSmithKline
Treatments:
Methylprednisolone
Methylprednisolone Acetate
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone acetate
Prednisolone hemisuccinate
Prednisolone phosphate
Criteria
Inclusion Criteria:

- Male or female between 18 and 75 years of age inclusive

- 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].

- Child-bearing potential and agrees to use one of the agreed contraception methods
listed in the protocol for an appropriate period of time to sufficiently minimize the
risk of pregnancy at that point. Female subjects must agree to use contraception for
at least 2 weeks prior to dosing and for at least 6 months after the last dose.

- Male subjects must agree to use one of the contraception methods listed in the
protocol. This criterion must be followed from the time of the first dose of study
medication until at least 60 days after the last dose.

- Blood test of liver function within normal range

- Body mass index within 18.5 - 35 kg/m2 inclusive

- Capable of giving informed consent and agreement to comply with the study restrictions

- 12-lead ECG within normal limits

- fT4 blood levels within reference range for at least 2 months

- Active Graves' Ophthalmopathy (GO) with a Clinical Activity Score (CAS) of >/= 3 out
of 7

- Moderately severe GO (as defined by EUGOGO guidelines)

- No previous immunosuppressive treatment for GO

- Subject is seropositive for EBV with <10,000 copies of EBV DNA per 10^6 lymphocytes
(qPCR) or seronegative with no evidence of acute EBV infection (asymptomatic, negative
EBV IgM and EBV viral load of <10,000 per 10^6 lymphocytes)

- The subject has no current or prior malignancy, other than non-melanoma skin cancer
(subject must have had fewer than 5 occurrences of non-melanoma skin cancer, and the
last occurrence must not be within 3 months of study entry)

Exclusion Criteria:

- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody
result within 3 months of screening

- Current or chronic history of liver disease, or known hepatic or biliary abnormalities
(with the exception of Gilbert's syndrome or asymptomatic gallstones)

- 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 test for HIV antibody

- Positive test for syphilis

- History of regular alcohol consumption within 6 months of the study defined as:

- an average weekly intake of greater than 21 units or an average daily intake of
greater than 3 units (males), or

- an average weekly intake of greater than 14 units or an average daily intake of
greater than 2 units (females)

- Participation 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) or planning to take any investigational drug for the
planned duration of study participation (6 months after the last dose of study drug)

- Exposure to more than four new chemical entities within 12 months prior to the first
dosing day

- 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

- Where participation in the study would result in donation of blood or blood products
in excess of 500 mL within a 56 day period

- Pregnant females as determined by positive (serum or urine) hCG test at screening or
prior to dosing, or lactating females

- Currently receiving or has received corticosteroids or other immunosuppressive agents
within the last 3 months

- Evidence of optic neuropathy and/or corneal breakdown

- Immunization with a vaccine within 30 days before the first dose of study drug or
requires a vaccine within 30 days after the last dose of study drug

- A CD4+ lymphocyte count outside the range of 0.53 - 1.76 × 109/L during screening

- Significant systemic infection during the 6 weeks before the first dose of study drug

- Received a course of oral antibiotics within 2 weeks of dosing day one

- History of recurrent or chronic infection

- Subject has had a splenectomy

- Subjects with a screening chest X-ray suggestive of TB without documentation of
adequate TB treatment

- Any major surgical procedure within the 8 weeks before signing the consent form, or
planning to undergo any such surgery within the 3 months after the last dose of study
drug

- Clinically significant cardiovascular and/or cerebrovascular disease

- Predisposition to thromboembolic disease, or thromboembolic event (excluding
superficial) in past 12 months

- Uncontrolled medical conditions: Significant concurrent, uncontrolled medical
condition including, but not limited to renal, hepatic, hematological,
gastrointestinal, endocrine, pulmonary, neurological, cerebral psychiatric disease, or
evidence of demyelinating disease

- A condition or situation that, in the investigator's judgment, is likely to cause the
subject to be unable or unwilling to participate in study procedures or to complete
all scheduled assessments

- Clinically significant abnormal laboratory values during the Screening period, other
than those due to GO. Abnormal values are permitted if, upon re-test, the abnormality
was resolved

- Unwillingness or inability to follow the procedures outlined in the protocol

- Mentally or legally incapacitated