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Trial record 5 of 9 for:    otelixizumab

A Safety and Tolerability Study of Otelixizumab in Thyroid Eye Disease

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ClinicalTrials.gov Identifier: NCT01114503
Recruitment Status : Terminated (Clinical study in Graves' ophthalmopathy terminated until there is a better understanding of an efficacious dose with Otelixizumab from other clinical studies.)
First Posted : May 3, 2010
Results First Posted : August 3, 2017
Last Update Posted : August 3, 2017
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Single (Outcomes Assessor);   Primary Purpose: Treatment
Condition Graves Ophthalmopathy
Interventions Drug: Otelixizumab - low dose
Drug: Otelixizumab - medium low dose
Drug: Otelixizumab - medium high dose
Drug: Otelixizumab - high dose
Drug: Otelixizumab
Drug: Methylprednisolone
Enrollment 2

Recruitment Details The study was conducted at a single center in United Kingdom from 23 June 2010 to 29 August 2012.
Pre-assignment Details A total of 2 participants were randomized in cohort A1 of the study. The study was early terminated due to the need of better understanding of an efficacious dose with otelixizumab from other clinical studies.
Arm/Group Title Otelixizumab Cohort A1
Hide Arm/Group Description Eligible participants received a total intravenous (IV) dose of otelixizumab 3.1 milligram (mg) for 8 days. The planned dosing regimen was 0.1 mg on Day 1, 0.2 mg on Day 2, 0.3 mg on Day 3, 0.5 mg on Day 4 to Day 8. The study medication was administered each day for 2 hours (h). The rate of infusion was 0.05 milligram per hour (mg/h) on Day 1, 0.1 mg/h on Day 2, 0.15 mg/h on Day 3, 0.25 mg/h on Day 4 to Day 8. At the start of each cohort in Part A, 2 participants acted as sentinel participants and complete dosing (Days 1–8) before further participants were dosed with otelixizumab. The first sentinel participants completed all of their dosing days and there was a minimum of 24 h elapse before the second sentinel participant started the dosing regimen. Further participants commenced dosing with otelixizumab once 24 h elapsed from the second sentinel participant receiving the final dose of otelixizumab on Day 8. Subsequent participants were dosed concurrently.
Period Title: Overall Study
Started 2
Completed 2
Not Completed 0
Arm/Group Title Otelixizumab Cohort A1
Hide Arm/Group Description Eligible participants received a IV dose of otelixizumab 3.1 mg for 8 days. The planned dosing regimen was 0.1 mg on Day 1, 0.2 mg on Day 2, 0.3 mg on Day 3, 0.5 mg on Day 4 to Day 8. The study medication was administered each day for 2 h. The rate of infusion was 0.05 mg/h on Day 1, 0.1 mg/h on Day 2, 0.15 mg/h on Day 3, 0.25 mg/h on Day 4 to Day 8. At the start of each cohort in Part A, 2 participants acted as sentinel participants and complete dosing (Days 1–8) before further participants were dosed with otelixizumab. The first sentinel participants completed all of their dosing days and there was a minimum of 24 h elapse before the second sentinel participant started the dosing regimen. Further participants commenced dosing with otelixizumab once 24 h elapsed from the second sentinel participant receiving the final dose of otelixizumab on Day 8. Subsequent participants were dosed concurrently.
Overall Number of Baseline Participants 2
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 2 participants
53.5
(53 to 54)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2 participants
Female
1
  50.0%
Male
1
  50.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2 participants
American Indian or Alaska Native
0
   0.0%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
0
   0.0%
White
2
 100.0%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
1.Primary Outcome
Title Number of Participants With at Least One Adverse Event (AE), Serious Adverse Event (SAE), or Drug-related Adverse Event
Hide Description An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect, may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition, associated with liver injury and impaired liver function defined as alanine aminotransferase >=3 x upper limit of normal (ULN), and total bilirubin >=2 x ULN or international normalized ratio >1.5. The classification as potentially drug-related was done based on the investigator's judgment.
Time Frame Up to Month 24 (Long term follow-up)
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Hide Analysis Population Description
All Subjects Population included all participants who receive at least one dose of study medication.
Arm/Group Title Otelixizumab Cohort A1
Hide Arm/Group Description:
Eligible participants received a IV dose of otelixizumab 3.1 mg for 8 days. The planned dosing regimen was 0.1 mg on Day 1, 0.2 mg on Day 2, 0.3 mg on Day 3, 0.5 mg on Day 4 to Day 8. The study medication was administered each day for 2 h. The rate of infusion was 0.05 mg/h on Day 1, 0.1 mg/h on Day 2, 0.15 mg/h on Day 3, 0.25 mg/h on Day 4 to Day 8. At the start of each cohort in Part A, 2 participants acted as sentinel participants and complete dosing (Days 1–8) before further participants were dosed with otelixizumab. The first sentinel participants completed all of their dosing days and there was a minimum of 24 h elapse before the second sentinel participant started the dosing regimen. Further participants commenced dosing with otelixizumab once 24 h elapsed from the second sentinel participant receiving the final dose of otelixizumab on Day 8. Subsequent participants were dosed concurrently.
Overall Number of Participants Analyzed 2
Measure Type: Number
Unit of Measure: Participants
Any AE 2
Any SAE 0
Any drug-related (AE) 2
2.Primary Outcome
Title Number of Participants With Laboratory Clinical Chemistry Abnormalities Meeting the Criteria for Potential Clinical Concern (PCC)
Hide Description The PCC range for clinical chemistry parameters included albumin, <30 gram per liter (g/L); calcium, low- < 2.0 millimole (mmol)/L: high->2.75 mmol/L; creatinine, high- > 1.3x ULN mmol/L or > 159 micromole (μmol)/L or > 44 μmol/L change from Baseline; glucose, low- < 3.0 mmol/L, high- > 9.0 0 mmol/L; magnesium, low- < 0.5 mmol/L, high- > 1.23 mmol/L, phosphorus, low- < 0.8 mmol/L, high- > 1.6 mmol/L; potassium, Low- < 3.0 mmol/L, high- > 5.5 mmol/L; sodium, low- < 130 mmol/L, high- > 150 mmol/L; bicarbonate, low- < 18 mmol/L, high- > 32 mmol/L; alanine aminotransferase, high->= 2x ULN, where the normal range was (NR) 0 – 39 international units (IU)/L; aspartate aminotransferase, high- >= 2x ULN, where NR was 0 – 39 IU/L; alkaline phosphatase, high- >= 1.5x ULN, where NR was 35 – 120 IU/L; total bilirubin- >= 1.5x ULN, where NR was 0 – 18 μmol/L.The assessments were done at Day 1 (pre dose), Day 8, Week 2-24 and Month 12 and 24.
Time Frame Up to Month 24 (Long term follow-up)
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All Subjects Population
Arm/Group Title Otelixizumab Cohort A1
Hide Arm/Group Description:
Eligible participants received a IV dose of otelixizumab 3.1 mg for 8 days. The planned dosing regimen was 0.1 mg on Day 1, 0.2 mg on Day 2, 0.3 mg on Day 3, 0.5 mg on Day 4 to Day 8. The study medication was administered each day for 2 h. The rate of infusion was 0.05 mg/h on Day 1, 0.1 mg/h on Day 2, 0.15 mg/h on Day 3, 0.25 mg/h on Day 4 to Day 8. At the start of each cohort in Part A, 2 participants acted as sentinel participants and complete dosing (Days 1–8) before further participants were dosed with otelixizumab. The first sentinel participants completed all of their dosing days and there was a minimum of 24 h elapse before the second sentinel participant started the dosing regimen. Further participants commenced dosing with otelixizumab once 24 h elapsed from the second sentinel participant receiving the final dose of otelixizumab on Day 8. Subsequent participants were dosed concurrently.
Overall Number of Participants Analyzed 2
Measure Type: Number
Unit of Measure: Participants
0
3.Primary Outcome
Title Number of Participants With Laboratory Hematology Abnormalities Meeting the Criteria for PCC
Hide Description The PCC range for hematology parameters included white blood cell count, low- < 3 giga cells (GI)/L, high- > 20 GI/L; neutrophil count, low- < 1.5 GI/L; hemoglobin, low- > 25 g/L change from baseline, high- 180 g/L; hematocrit, low- > 0.075 L change from baseline, high- 0.54 L; platelet count, low- < 100 GI/L, high- >550 GI/L and lymphocytes, low < 0.8 GI/L. The assessments were done at Day 1 (pre dose), Day 8, Week 2-24, Month 12 and 24.
Time Frame Upto Month 24 (Long term follow-up)
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Hide Analysis Population Description
All Subjects Population
Arm/Group Title Otelixizumab Cohort A1
Hide Arm/Group Description:
Eligible participants received a IV dose of otelixizumab 3.1 mg for 8 days. The planned dosing regimen was 0.1 mg on Day 1, 0.2 mg on Day 2, 0.3 mg on Day 3, 0.5 mg on Day 4 to Day 8. The study medication was administered each day for 2 h. The rate of infusion was 0.05 mg/h on Day 1, 0.1 mg/h on Day 2, 0.15 mg/h on Day 3, 0.25 mg/h on Day 4 to Day 8. At the start of each cohort in Part A, 2 participants acted as sentinel participants and complete dosing (Days 1–8) before further participants were dosed with otelixizumab. The first sentinel participants completed all of their dosing days and there was a minimum of 24 h elapse before the second sentinel participant started the dosing regimen. Further participants commenced dosing with otelixizumab once 24 h elapsed from the second sentinel participant receiving the final dose of otelixizumab on Day 8. Subsequent participants were dosed concurrently.
Overall Number of Participants Analyzed 2
Measure Type: Number
Unit of Measure: Participants
0
4.Primary Outcome
Title Number of Participants With Laboratory Urinalysis Abnormalities Meeting the Criteria for PCC
Hide Description The urinalysis parameters included pH, glucose, protein, blood and ketones by dipstic and microscopy (if urine dipstick was positive for blood or protein). The assessments were done at Day 1 (pre dose), Day 8, Week 2-24, Month 12 and 24.
Time Frame Up to Month 24 (Long term follow-up)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All Subjects Population
Arm/Group Title Otelixizumab Cohort A1
Hide Arm/Group Description:
Eligible participants received a IV dose of otelixizumab 3.1 mg for 8 days. The planned dosing regimen was 0.1 mg on Day 1, 0.2 mg on Day 2, 0.3 mg on Day 3, 0.5 mg on Day 4 to Day 8. The study medication was administered each day for 2 h. The rate of infusion was 0.05 mg/h on Day 1, 0.1 mg/h on Day 2, 0.15 mg/h on Day 3, 0.25 mg/h on Day 4 to Day 8. At the start of each cohort in Part A, 2 participants acted as sentinel participants and complete dosing (Days 1–8) before further participants were dosed with otelixizumab. The first sentinel participants completed all of their dosing days and there was a minimum of 24 h elapse before the second sentinel participant started the dosing regimen. Further participants commenced dosing with otelixizumab once 24 h elapsed from the second sentinel participant receiving the final dose of otelixizumab on Day 8. Subsequent participants were dosed concurrently.
Overall Number of Participants Analyzed 2
Measure Type: Number
Unit of Measure: Participants
0
5.Primary Outcome
Title Number of Participants With Thyroid Function Assessment, Hormone and Glucose Assay Abnormalities Meeting the Criteria for PCC
Hide Description The following laboratory parameters were analyzed: thyroid function assessment (thyroid stimulating hormone [TSH], thyroid peroxidase antibody, thyrotropin receptor antibodies (TSH-R-Abs) or TSH-binding inhibiting immunoglobulin (TBII), free thyroxine [fT4], free triiodothyronine [fT3]; hormone and glucose assays (cortisol, adrenocorticotrophic hormone [ACTH], insulin-like growth factor [IgF-1] and plasma glucose. Thyroid function tests were done at Day 1 (pre-dose) and Week 4-24. Hormone and glucose assays were done at Day 1 (pre-dose) and Week 2-24.
Time Frame Up to Week 24
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Hide Analysis Population Description
All Subjects Population
Arm/Group Title Otelixizumab Cohort A1
Hide Arm/Group Description:
Eligible participants received a IV dose of otelixizumab 3.1 mg for 8 days. The planned dosing regimen was 0.1 mg on Day 1, 0.2 mg on Day 2, 0.3 mg on Day 3, 0.5 mg on Day 4 to Day 8. The study medication was administered each day for 2 h. The rate of infusion was 0.05 mg/h on Day 1, 0.1 mg/h on Day 2, 0.15 mg/h on Day 3, 0.25 mg/h on Day 4 to Day 8. At the start of each cohort in Part A, 2 participants acted as sentinel participants and complete dosing (Days 1–8) before further participants were dosed with otelixizumab. The first sentinel participants completed all of their dosing days and there was a minimum of 24 h elapse before the second sentinel participant started the dosing regimen. Further participants commenced dosing with otelixizumab once 24 h elapsed from the second sentinel participant receiving the final dose of otelixizumab on Day 8. Subsequent participants were dosed concurrently.
Overall Number of Participants Analyzed 2
Measure Type: Number
Unit of Measure: Participants
0
6.Primary Outcome
Title Number of Participants With Vital Signs Abnormalities Meeting the Criteria for PCC
Hide Description Vital signs assessment included pulse rate, blood pressure, temperature and respiratory rate. Criteria for vital sign values meeting potential clinical concern included: supine pulse rate <40 or >110 beats per minute (bpm), >= 15 increase from baseline and >= 30 decrease from baseline; systolic blood pressure (SBP) < 85 and > 160 millimeters of mercury (mm Hg), >= 20 mmHg increase from baseline and >= 40 mmHg decrease from baseline; diastolic blood pressure (DBP) < 45 and > 100 mm Hg, >= 10 mmHg increase from baseline and >= 20 mmHg decrease from baseline.
Time Frame Up to Month 24 (Long term follow-up)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All Subjects Population
Arm/Group Title Otelixizumab Cohort A1
Hide Arm/Group Description:
Eligible participants received a IV dose of otelixizumab 3.1 mg for 8 days. The planned dosing regimen was 0.1 mg on Day 1, 0.2 mg on Day 2, 0.3 mg on Day 3, 0.5 mg on Day 4 to Day 8. The study medication was administered each day for 2 h. The rate of infusion was 0.05 mg/h on Day 1, 0.1 mg/h on Day 2, 0.15 mg/h on Day 3, 0.25 mg/h on Day 4 to Day 8. At the start of each cohort in Part A, 2 participants acted as sentinel participants and complete dosing (Days 1–8) before further participants were dosed with otelixizumab. The first sentinel participants completed all of their dosing days and there was a minimum of 24 h elapse before the second sentinel participant started the dosing regimen. Further participants commenced dosing with otelixizumab once 24 h elapsed from the second sentinel participant receiving the final dose of otelixizumab on Day 8. Subsequent participants were dosed concurrently.
Overall Number of Participants Analyzed 2
Measure Type: Number
Unit of Measure: Participants
0
7.Primary Outcome
Title Number of Participants With Electrocardiogram (ECG) Abnormalities Meeting the Criteria for PCC
Hide Description ECG parameters included pulse rate (PR) interval, QRS interval, QT interval, corrected QT interval using Bazett's formula (QTcB) and corrected QT interval using Fridericia's formula (QTcF). Criteria for ECG changes meeting potential clinical concern included: PR interval <110 and >220 milliseconds (msec); QRS interval <75 and >110 msec; QTc interval >480 to <= 500 msec, increase from baseline QTc >30 to <= 60 msec.
Time Frame Screening (Day –35 to Day –1)
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Hide Analysis Population Description
All Subjects Population
Arm/Group Title Otelixizumab Cohort A1
Hide Arm/Group Description:
Eligible participants received a IV dose of otelixizumab 3.1 mg for 8 days. The planned dosing regimen was 0.1 mg on Day 1, 0.2 mg on Day 2, 0.3 mg on Day 3, 0.5 mg on Day 4 to Day 8. The study medication was administered each day for 2 h. The rate of infusion was 0.05 mg/h on Day 1, 0.1 mg/h on Day 2, 0.15 mg/h on Day 3, 0.25 mg/h on Day 4 to Day 8. At the start of each cohort in Part A, 2 participants acted as sentinel participants and complete dosing (Days 1–8) before further participants were dosed with otelixizumab. The first sentinel participants completed all of their dosing days and there was a minimum of 24 h elapse before the second sentinel participant started the dosing regimen. Further participants commenced dosing with otelixizumab once 24 h elapsed from the second sentinel participant receiving the final dose of otelixizumab on Day 8. Subsequent participants were dosed concurrently.
Overall Number of Participants Analyzed 2
Measure Type: Number
Unit of Measure: Participants
0
8.Primary Outcome
Title Number of Participants With an Epstein Barr Virus (EBV) Viral Load Abnormalities Meeting the Criteria for PCC
Hide Description The PCC range for EBV viral load was > 10,000 copies of deoxyribonucleic acid (DNA) per million lymphocytes. The assessments were done at Week 2, Week 4, Week 8 and Week 12.
Time Frame Week 2 to Week 12
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Hide Analysis Population Description
All Subjects Population
Arm/Group Title Otelixizumab Cohort A1
Hide Arm/Group Description:
Eligible participants received a IV dose of otelixizumab 3.1 mg for 8 days. The planned dosing regimen was 0.1 mg on Day 1, 0.2 mg on Day 2, 0.3 mg on Day 3, 0.5 mg on Day 4 to Day 8. The study medication was administered each day for 2 h. The rate of infusion was 0.05 mg/h on Day 1, 0.1 mg/h on Day 2, 0.15 mg/h on Day 3, 0.25 mg/h on Day 4 to Day 8. At the start of each cohort in Part A, 2 participants acted as sentinel participants and complete dosing (Days 1–8) before further participants were dosed with otelixizumab. The first sentinel participants completed all of their dosing days and there was a minimum of 24 h elapse before the second sentinel participant started the dosing regimen. Further participants commenced dosing with otelixizumab once 24 h elapsed from the second sentinel participant receiving the final dose of otelixizumab on Day 8. Subsequent participants were dosed concurrently.
Overall Number of Participants Analyzed 2
Measure Type: Number
Unit of Measure: Participants
0
9.Primary Outcome
Title Individual Absolute Circulating Peripheral T Lymphocytes (T-cells), CD4+ and CD8+ Subset Counts
Hide Description The lymphocyte subsets of T-cells, CD4+ and CD8+ cells were planned to be assessed at Day 1 (pre dose), Day 8 (pre dose), Week 2, Week 4, Week 8, Week 12 and Week 24. The absolute counts of the relevant lymphocyte subsets was to be determined by multiplying the percentages of the cell subsets with total lymphocyte counts. The percentages of relevant lymphocyte subsets was to be determined by flow cytometry. This endpoint was not analyzed due to the early termination of the study and since only 2 participants were recruited.
Time Frame Up to Week 24
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Hide Analysis Population Description
All Subjects Population. No participants were available for analysis because of early termination of study.
Arm/Group Title Otelixizumab Cohort A1
Hide Arm/Group Description:
Eligible participants received a IV dose of otelixizumab 3.1 mg for 8 days. The planned dosing regimen was 0.1 mg on Day 1, 0.2 mg on Day 2, 0.3 mg on Day 3, 0.5 mg on Day 4 to Day 8. The study medication was administered each day for 2 h. The rate of infusion was 0.05 mg/h on Day 1, 0.1 mg/h on Day 2, 0.15 mg/h on Day 3, 0.25 mg/h on Day 4 to Day 8. At the start of each cohort in Part A, 2 participants acted as sentinel participants and complete dosing (Days 1–8) before further participants were dosed with otelixizumab. The first sentinel participants completed all of their dosing days and there was a minimum of 24 h elapse before the second sentinel participant started the dosing regimen. Further participants commenced dosing with otelixizumab once 24 h elapsed from the second sentinel participant receiving the final dose of otelixizumab on Day 8. Subsequent participants were dosed concurrently.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
10.Primary Outcome
Title Percentage of Circulating Peripheral T-cells, CD4+ and CD8+ Subset Counts
Hide Description The lymphocyte subsets of T-cells, CD4+ and CD8+ cells were planned to be assessed at Day 1 (pre dose), Day 8 (pre dose), Week 2, Week 4, Week 8, Week 12 and Week 24. The percentages of relevant lymphocyte subsets was to be determined by flow cytometry. This endpoint was not analyzed due to the early termination of the study and since only 2 participants were recruited.
Time Frame Up to Week 24
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Hide Analysis Population Description
All Subjects Population. No participants were available for analysis because of early termination of study.
Arm/Group Title Otelixizumab Cohort A1
Hide Arm/Group Description:
Eligible participants received a IV dose of otelixizumab 3.1 mg for 8 days. The planned dosing regimen was 0.1 mg on Day 1, 0.2 mg on Day 2, 0.3 mg on Day 3, 0.5 mg on Day 4 to Day 8. The study medication was administered each day for 2 h. The rate of infusion was 0.05 mg/h on Day 1, 0.1 mg/h on Day 2, 0.15 mg/h on Day 3, 0.25 mg/h on Day 4 to Day 8. At the start of each cohort in Part A, 2 participants acted as sentinel participants and complete dosing (Days 1–8) before further participants were dosed with otelixizumab. The first sentinel participants completed all of their dosing days and there was a minimum of 24 h elapse before the second sentinel participant started the dosing regimen. Further participants commenced dosing with otelixizumab once 24 h elapsed from the second sentinel participant receiving the final dose of otelixizumab on Day 8. Subsequent participants were dosed concurrently.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
11.Primary Outcome
Title Assessment of CD3/T-cell Receptor (TCR) Complex Saturation and Modulation
Hide Description The assessment of CD3/TCR complex saturation and modulation was planned to be assessed on Day (1-8) pre dose, Week 2, Week 4, Week 8, Week 12 and Week 24. The extent of modulation was to be determined by the extent of TCR alpha beta (αβ) expression which was proportional to the combined levels of free CD3 sites and bound otelixizumab to CD4+ and CD8+ T cells. Bound levels of otelixizumab was planned to be determined by using flow cytometry method using an anti Immunoglobulin (Ig) antibody. The molecules of equivalent soluble fluorochrome (MESF) of the anti-Ig antibody was to be used to quantify the levels of bound otelixizumab present on T cells. Free otelixizumab binding sites (i.e., sites not occupied by otelixizumab administered to the participants) was to be detected by staining with fluorescein isothiocyanate (FITC) labelled otelixizumab. This endpoint was not analyzed due to the early termination of the study and since only 2 participants were recruited.
Time Frame Up to Week 24
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Hide Analysis Population Description
All Subjects Population. No participants were available for analysis because of early termination of study.
Arm/Group Title Otelixizumab Cohort A1
Hide Arm/Group Description:
Eligible participants received a IV dose of otelixizumab 3.1 mg for 8 days. The planned dosing regimen was 0.1 mg on Day 1, 0.2 mg on Day 2, 0.3 mg on Day 3, 0.5 mg on Day 4 to Day 8. The study medication was administered each day for 2 h. The rate of infusion was 0.05 mg/h on Day 1, 0.1 mg/h on Day 2, 0.15 mg/h on Day 3, 0.25 mg/h on Day 4 to Day 8. At the start of each cohort in Part A, 2 participants acted as sentinel participants and complete dosing (Days 1–8) before further participants were dosed with otelixizumab. The first sentinel participants completed all of their dosing days and there was a minimum of 24 h elapse before the second sentinel participant started the dosing regimen. Further participants commenced dosing with otelixizumab once 24 h elapsed from the second sentinel participant receiving the final dose of otelixizumab on Day 8. Subsequent participants were dosed concurrently.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
12.Secondary Outcome
Title Change From Baseline for Individual Scores at Week 12 Incorporated in the European Group on Graves’ Orbitopathy (EUGOGO) Assessment Including, Eyelid Swelling, Clinical Activity Score (CAS) Score, Proptosis, Lid Width and Diplopia
Hide Description The EUGOGO assessment of change was defined by improvement or deterioration of clinical scores. Improvement in EUGOGO was defined as improvement in two of the following measures in at least one eye, without deterioration in any of the same measures in both eyes: eyelid swelling according to color atlas evaluation, CAS by at least 2 points, proptosis by at least 2 millimeter (mm) by Hertel exophthalmometer, lid width by at least 2 mm, diplopia (disappearance or change in the degree) or improvement of >=8 degrees in motility unexplained by commensurate deterioration of motility of ipsilateral antagonists. Deterioration was defined by worsening by same quantity (as for improvement) of the same measures. Baseline was referred to assessment on Day 1 (pre dose). Change from Baseline was defined as post-Baseline value minus Baseline value. This endpoint was not analyzed due to the early termination of the study and since only 2 participants were recruited.
Time Frame Baseline (Day 1, pre dose) and Week 12
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Hide Analysis Population Description
All Subjects Population. No participants were available for analysis because of early termination of study.
Arm/Group Title Otelixizumab Cohort A1
Hide Arm/Group Description:
Eligible participants received a IV dose of otelixizumab 3.1 mg for 8 days. The planned dosing regimen was 0.1 mg on Day 1, 0.2 mg on Day 2, 0.3 mg on Day 3, 0.5 mg on Day 4 to Day 8. The study medication was administered each day for 2 h. The rate of infusion was 0.05 mg/h on Day 1, 0.1 mg/h on Day 2, 0.15 mg/h on Day 3, 0.25 mg/h on Day 4 to Day 8. At the start of each cohort in Part A, 2 participants acted as sentinel participants and complete dosing (Days 1–8) before further participants were dosed with otelixizumab. The first sentinel participants completed all of their dosing days and there was a minimum of 24 h elapse before the second sentinel participant started the dosing regimen. Further participants commenced dosing with otelixizumab once 24 h elapsed from the second sentinel participant receiving the final dose of otelixizumab on Day 8. Subsequent participants were dosed concurrently.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
13.Secondary Outcome
Title Change From Baseline for Participant-reported Health Related Quality of Life (QoL) Questionnaires of Short Form 36 ( SF-36) and Graves Ophthalmopathy (GO) QoL
Hide Description Assessment of health related QoL was planned to be evaluated using the validated, disease specific, GO-QoL questionnaire and the SF-36 health survey questionnaire at Day 1 (pre dose) and Week 2- 24. Mean scores range from 0 (minimum) - 100 (maximum) with higher mean scores reflected better outcomes. Baseline was referred to assessment on Day 1 (pre dose). Change from Baseline was defined as post-Baseline value minus Baseline value. This endpoint was not analyzed due to the early termination of the study and since only 2 participants were recruited.
Time Frame Baseline (Day 1, pre dose) to Week 24
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Hide Analysis Population Description
All Subjects Population. No participants were available for analysis because of early termination of study.
Arm/Group Title Otelixizumab Cohort A1
Hide Arm/Group Description:
Eligible participants received a IV dose of otelixizumab 3.1 mg for 8 days. The planned dosing regimen was 0.1 mg on Day 1, 0.2 mg on Day 2, 0.3 mg on Day 3, 0.5 mg on Day 4 to Day 8. The study medication was administered each day for 2 h. The rate of infusion was 0.05 mg/h on Day 1, 0.1 mg/h on Day 2, 0.15 mg/h on Day 3, 0.25 mg/h on Day 4 to Day 8. At the start of each cohort in Part A, 2 participants acted as sentinel participants and complete dosing (Days 1–8) before further participants were dosed with otelixizumab. The first sentinel participants completed all of their dosing days and there was a minimum of 24 h elapse before the second sentinel participant started the dosing regimen. Further participants commenced dosing with otelixizumab once 24 h elapsed from the second sentinel participant receiving the final dose of otelixizumab on Day 8. Subsequent participants were dosed concurrently.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
14.Secondary Outcome
Title Change From Baseline Measurement of Orbital Volume as Measured by Computed Tomography (CT) Scan
Hide Description The assessment of orbital volume measured by CT scan was planned to be assessed on Week 12 and Week 24. Baseline was referred to assessment at Screening. Change from Baseline was defined as post-Baseline value minus Baseline value. This endpoint was not analyzed due to the early termination of the study and since only 2 participants were recruited.
Time Frame Baseline (Screening), Week 12 and Week 24
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Hide Analysis Population Description
All Subjects Population. No participants were available for analysis because of early termination of study.
Arm/Group Title Otelixizumab Cohort A1
Hide Arm/Group Description:
Eligible participants received a IV dose of otelixizumab 3.1 mg for 8 days. The planned dosing regimen was 0.1 mg on Day 1, 0.2 mg on Day 2, 0.3 mg on Day 3, 0.5 mg on Day 4 to Day 8. The study medication was administered each day for 2 h. The rate of infusion was 0.05 mg/h on Day 1, 0.1 mg/h on Day 2, 0.15 mg/h on Day 3, 0.25 mg/h on Day 4 to Day 8. At the start of each cohort in Part A, 2 participants acted as sentinel participants and complete dosing (Days 1–8) before further participants were dosed with otelixizumab. The first sentinel participants completed all of their dosing days and there was a minimum of 24 h elapse before the second sentinel participant started the dosing regimen. Further participants commenced dosing with otelixizumab once 24 h elapsed from the second sentinel participant receiving the final dose of otelixizumab on Day 8. Subsequent participants were dosed concurrently.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
15.Secondary Outcome
Title Assessment of Anti-otelixizumab Antibodies
Hide Description Anti-otelixizumab antibodies were planned to be assessed on Day 1 (pre dose), Day 8 (pre dose), Week 4-24 and Month 12. This endpoint was not analyzed due to the early termination of the study and since only 2 participants were recruited.
Time Frame Up to Month 12
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Hide Analysis Population Description
All Subjects Population. No participants were available for analysis because of early termination of study.
Arm/Group Title Otelixizumab Cohort A1
Hide Arm/Group Description:
Eligible participants received a IV dose of otelixizumab 3.1 mg for 8 days. The planned dosing regimen was 0.1 mg on Day 1, 0.2 mg on Day 2, 0.3 mg on Day 3, 0.5 mg on Day 4 to Day 8. The study medication was administered each day for 2 h. The rate of infusion was 0.05 mg/h on Day 1, 0.1 mg/h on Day 2, 0.15 mg/h on Day 3, 0.25 mg/h on Day 4 to Day 8. At the start of each cohort in Part A, 2 participants acted as sentinel participants and complete dosing (Days 1–8) before further participants were dosed with otelixizumab. The first sentinel participants completed all of their dosing days and there was a minimum of 24 h elapse before the second sentinel participant started the dosing regimen. Further participants commenced dosing with otelixizumab once 24 h elapsed from the second sentinel participant receiving the final dose of otelixizumab on Day 8. Subsequent participants were dosed concurrently.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
16.Secondary Outcome
Title Assessment of Circulating Cytokines of Interleukin 6 (IL6), IL10, Interferon Gamma (IFNγ) and Tumor Necrosis Factor Alpha (TNFα) up to 2 Weeks
Hide Description Assessment of circulating cytokines of IL6, IL10, IFNγ and TNFα was planned to be assessed on Day 1-8 (pre dose) and Week 12. This endpoint was not analyzed due to the early termination of the study and since only 2 participants were recruited.
Time Frame Up to Week 2
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Hide Analysis Population Description
All Subjects Population. No participants were available for analysis because of early termination of study.
Arm/Group Title Otelixizumab Cohort A1
Hide Arm/Group Description:
Eligible participants received a IV dose of otelixizumab 3.1 mg for 8 days. The planned dosing regimen was 0.1 mg on Day 1, 0.2 mg on Day 2, 0.3 mg on Day 3, 0.5 mg on Day 4 to Day 8. The study medication was administered each day for 2 h. The rate of infusion was 0.05 mg/h on Day 1, 0.1 mg/h on Day 2, 0.15 mg/h on Day 3, 0.25 mg/h on Day 4 to Day 8. At the start of each cohort in Part A, 2 participants acted as sentinel participants and complete dosing (Days 1–8) before further participants were dosed with otelixizumab. The first sentinel participants completed all of their dosing days and there was a minimum of 24 h elapse before the second sentinel participant started the dosing regimen. Further participants commenced dosing with otelixizumab once 24 h elapsed from the second sentinel participant receiving the final dose of otelixizumab on Day 8. Subsequent participants were dosed concurrently.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
17.Secondary Outcome
Title Assessment of Exploratory Biomarkers
Hide Description The exploratory biomarkers were planned to be assessed on Day 1 (pre dose), Week 4, Week 12 and Week 24. It included assessment of peripheral blood mononuclear cells (PBMC) markers, suppression assays for the measure of effector cell proliferation, quantification of effector memory T-cells subsets, autoreactivity assays using cytokine production of supernatants and CFSE dilution, cytokine production by in-vitro stimulated T-cells, circulating serum biomarkers and may include subsequently discovered biomarkers of the biological response associated with GO or medically related conditions and/or the action of otelixizumab. This endpoint was not analyzed due to the early termination of the study and since only 2 participants were recruited.
Time Frame Up to Week 24
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Hide Analysis Population Description
All Subjects Population. No participants were available for analysis because of early termination of study.
Arm/Group Title Otelixizumab Cohort A1
Hide Arm/Group Description:
Eligible participants received a IV dose of otelixizumab 3.1 mg for 8 days. The planned dosing regimen was 0.1 mg on Day 1, 0.2 mg on Day 2, 0.3 mg on Day 3, 0.5 mg on Day 4 to Day 8. The study medication was administered each day for 2 h. The rate of infusion was 0.05 mg/h on Day 1, 0.1 mg/h on Day 2, 0.15 mg/h on Day 3, 0.25 mg/h on Day 4 to Day 8. At the start of each cohort in Part A, 2 participants acted as sentinel participants and complete dosing (Days 1–8) before further participants were dosed with otelixizumab. The first sentinel participants completed all of their dosing days and there was a minimum of 24 h elapse before the second sentinel participant started the dosing regimen. Further participants commenced dosing with otelixizumab once 24 h elapsed from the second sentinel participant receiving the final dose of otelixizumab on Day 8. Subsequent participants were dosed concurrently.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
18.Secondary Outcome
Title Assessment of Exploratory Biomarkers of Ribonucleic Acid (RNA) Transcription Analysis of Peripheral Blood
Hide Description The exploratory biomarkers of RNA transcription analysis of peripheral blood was planned to be assessed on Day 1(pre dose), Week 4 and Week 24. The assessment was to be done using microarray and RNA expression using quantitative reverse transcription polymerase chain reaction (RT-PCR). This endpoint was not analyzed due to the early termination of the study and since only 2 participants were recruited.
Time Frame Up to Week 24
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Hide Analysis Population Description
All Subjects Population. No participants were available for analysis because of early termination of study.
Arm/Group Title Otelixizumab Cohort A1
Hide Arm/Group Description:
Eligible participants received a IV dose of otelixizumab 3.1 mg for 8 days. The planned dosing regimen was 0.1 mg on Day 1, 0.2 mg on Day 2, 0.3 mg on Day 3, 0.5 mg on Day 4 to Day 8. The study medication was administered each day for 2 h. The rate of infusion was 0.05 mg/h on Day 1, 0.1 mg/h on Day 2, 0.15 mg/h on Day 3, 0.25 mg/h on Day 4 to Day 8. At the start of each cohort in Part A, 2 participants acted as sentinel participants and complete dosing (Days 1–8) before further participants were dosed with otelixizumab. The first sentinel participants completed all of their dosing days and there was a minimum of 24 h elapse before the second sentinel participant started the dosing regimen. Further participants commenced dosing with otelixizumab once 24 h elapsed from the second sentinel participant receiving the final dose of otelixizumab on Day 8. Subsequent participants were dosed concurrently.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame AE's and SAE's were recorded from Day 1 up to Month 24
Adverse Event Reporting Description All Subjects Population was used.
 
Arm/Group Title Otelixizumab Cohort A1
Hide Arm/Group Description Eligible participants received a IV dose of otelixizumab 3.1 mg for 8 days. The planned dosing regimen was 0.1 mg on Day 1, 0.2 mg on Day 2, 0.3 mg on Day 3, 0.5 mg on Day 4 to Day 8. The study medication was administered each day for 2 h. The rate of infusion was 0.05 mg/h on Day 1, 0.1 mg/h on Day 2, 0.15 mg/h on Day 3, 0.25 mg/h on Day 4 to Day 8. At the start of each cohort in Part A, 2 participants acted as sentinel participants and complete dosing (Days 1–8) before further participants were dosed with otelixizumab. The first sentinel participants completed all of their dosing days and there was a minimum of 24 h elapse before the second sentinel participant started the dosing regimen. Further participants commenced dosing with otelixizumab once 24 h elapsed from the second sentinel participant receiving the final dose of otelixizumab on Day 8. Subsequent participants were dosed concurrently.
All-Cause Mortality
Otelixizumab Cohort A1
Affected / at Risk (%)
Total   0/2 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
Otelixizumab Cohort A1
Affected / at Risk (%)
Total   0/2 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
Otelixizumab Cohort A1
Affected / at Risk (%)
Total   2/2 (100.00%) 
Ear and labyrinth disorders   
Vertigo positional  1  1/2 (50.00%) 
Eye disorders   
Foreign body sensation in eyes  1  2/2 (100.00%) 
Eye Pain  1  1/2 (50.00%) 
Nervous system disorders   
Headache  1  2/2 (100.00%) 
Vascular disorders   
Hot Flush  1  1/2 (50.00%) 
1
Term from vocabulary, MedDRA
Indicates events were collected by systematic assessment
The study was terminated due to the need of better understanding of an efficacious dose with otelixizumab from other clinical studies.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Results Point of Contact
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
Phone: 866-435-7343
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01114503     History of Changes
Other Study ID Numbers: 112480
First Submitted: April 29, 2010
First Posted: May 3, 2010
Results First Submitted: March 2, 2017
Results First Posted: August 3, 2017
Last Update Posted: August 3, 2017