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| ID | Type | Description | Link |
|---|---|---|---|
| 2009-016747-19 | EudraCT Number |
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Clinical study in Graves' ophthalmopathy terminated until there is a better understanding of an efficacious dose with Otelixizumab from other clinical studies.
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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.
This is a study of otelixizumab, a monoclonal antibody (MAb) directed against the human lymphocyte antigen CD3 (a protein found on a certain type of white blood cell). This will be an open-label, comparator-controlled, two part study to evaluate the safety and tolerability of otelixizumab in patients with Graves' ophthalmopathy (GO). It will also look to see if otelixizumab affects GO and how it works compared to methylprednisolone (the standard treatment for active GO).
In Part A, between one and four groups of 5 patients will receive doses of otelixizumab administered over 8 days. The first dose level will provide a low cumulative dose, this low dose level has been safely administered in previous studies. Safety and clinical response data will be reviewed after 8 weeks, if no clinical response is seen and there are no safety concerns, the dose of otelixizumab will be increased and a new group of subjects will enter Part A. In subsequent groups cumulative medium low, medium high, and high doses of otelixizumab may be investigated. However if a clinical response is seen at the lowest dose the study will move directly to Part B.
In Part B, patients will receive either otelixizumab at the dose set from Part A, over 8 days (5 patients) or methylprednisolone weekly for 12 weeks (5 patients). All dosing will be by intravenous infusion. All participants will undergo long term safety evaluation for 48 months.
Key assessments include vital signs, 12-lead ECG, liver function tests, thyroid function, viral monitoring, monitoring of cortisol and ACTH levels, laboratory safety tests and adverse event (side effect) data. Assessment of GO severity will be evaluated using recommended assessments including clinical activity assessments and quality of life questionnaires. Measurements of exploratory biomarkers (proteins found naturally in the blood) are also included in this study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part A | Experimental | Up to 4 cohorts of 5 patients receive dose rising treatments of otelixizumab |
|
| Part B - Otelixizumab | Experimental | Parallel dosing group in Part B receive otelixizumab over 8 days at a dose decided upon results from Part A |
|
| Part B - Methylprednisolone | Active Comparator | Parallel dosing group in Part B of weekly doses of methylprednisolone for 12 weeks |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Otelixizumab - low dose | Drug | 8 day dose rising intravenous infusions of a low dose of otelixizumab |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With at Least One Adverse Event (AE), Serious Adverse Event (SAE), or Drug-related Adverse Event | 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. | Up to Month 24 (Long term follow-up) |
| Number of Participants With Laboratory Clinical Chemistry Abnormalities Meeting the Criteria for Potential Clinical Concern (PCC) | 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. | Up to Month 24 (Long term follow-up) |
| Number of Participants With Laboratory Hematology Abnormalities Meeting the Criteria for PCC | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Newcastle upon Tyne | NE1 3BZ | United Kingdom |
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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.
The study was conducted at a single center in United Kingdom from 23 June 2010 to 29 August 2012.
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| ID | Title | Description |
|---|---|---|
| FG000 | Otelixizumab Cohort A1 | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Otelixizumab Cohort A1 | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With at Least One Adverse Event (AE), Serious Adverse Event (SAE), or Drug-related Adverse Event | 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. | All Subjects Population included all participants who receive at least one dose of study medication. | Posted | Number | Participants | Up to Month 24 (Long term follow-up) |
AE's and SAE's were recorded from Day 1 up to Month 24
All Subjects Population was used.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Otelixizumab Cohort A1 | 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. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | MedDRA | Systematic Assessment |
The study was terminated due to the need of better understanding of an efficacious dose with otelixizumab from other clinical studies.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| GSK Response Center | GlaxoSmithKline | 866-435-7343 |
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| ID | Term |
|---|---|
| D049970 | Graves Ophthalmopathy |
| ID | Term |
|---|---|
| D015785 | Eye Diseases, Hereditary |
| D005128 | Eye Diseases |
| D006111 | Graves Disease |
| D005094 | Exophthalmos |
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| ID | Term |
|---|---|
| C550701 | otelixizumab |
| D008775 | Methylprednisolone |
| ID | Term |
|---|---|
| D011239 | Prednisolone |
| D011246 | Pregnadienetriols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
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| Otelixizumab - medium low dose | Drug | 8 day dose rising intravenous infusions of a medium low dose of otelixizumab |
|
| Otelixizumab - medium high dose | Drug | 8 day dose rising intravenous infusions of a medium high dose of otelixizumab |
|
| Otelixizumab - high dose | Drug | 8 day dose rising intravenous infusions of a high dose of otelixizumab |
|
| Otelixizumab | Drug | 8 day dose rising intravenous infusions of otelixizumab administered at a dose decided upon results from Part A. |
|
| Methylprednisolone | Drug | Weekly intravenous infusions of methylprednisolone administered as 500 mg per week for 6 weeks and then 250 mg per week for 6 weeks |
|
| Upto Month 24 (Long term follow-up) |
| Number of Participants With Laboratory Urinalysis Abnormalities Meeting the Criteria for PCC | 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. | Up to Month 24 (Long term follow-up) |
| Number of Participants With Thyroid Function Assessment, Hormone and Glucose Assay Abnormalities Meeting the Criteria for PCC | 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. | Up to Week 24 |
| Number of Participants With Vital Signs Abnormalities Meeting the Criteria for PCC | 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. | Up to Month 24 (Long term follow-up) |
| Number of Participants With Electrocardiogram (ECG) Abnormalities Meeting the Criteria for PCC | 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. | Screening (Day -35 to Day -1) |
| Number of Participants With an Epstein Barr Virus (EBV) Viral Load Abnormalities Meeting the Criteria for PCC | 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. | Week 2 to Week 12 |
| Individual Absolute Circulating Peripheral T Lymphocytes (T-cells), CD4+ and CD8+ Subset Counts | 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. | Up to Week 24 |
| Percentage of Circulating Peripheral T-cells, CD4+ and CD8+ Subset Counts | 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. | Up to Week 24 |
| Assessment of CD3/T-cell Receptor (TCR) Complex Saturation and Modulation | 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. | Up to Week 24 |
| Baseline (Day 1, pre dose) and Week 12 |
| Change From Baseline for Participant-reported Health Related Quality of Life (QoL) Questionnaires of Short Form 36 ( SF-36) and Graves Ophthalmopathy (GO) QoL | 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. | Baseline (Day 1, pre dose) to Week 24 |
| Change From Baseline Measurement of Orbital Volume as Measured by Computed Tomography (CT) Scan | 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. | Baseline (Screening), Week 12 and Week 24 |
| Assessment of Anti-otelixizumab Antibodies | 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. | Up to Month 12 |
| Assessment of Circulating Cytokines of Interleukin 6 (IL6), IL10, Interferon Gamma (IFNγ) and Tumor Necrosis Factor Alpha (TNFα) up to 2 Weeks | 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. | Up to Week 2 |
| Assessment of Exploratory Biomarkers | 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. | Up to Week 24 |
| Assessment of Exploratory Biomarkers of Ribonucleic Acid (RNA) Transcription Analysis of Peripheral Blood | 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. | Up to Week 24 |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| ID |
|---|
| Title |
|---|
| Description |
|---|
| OG000 | Otelixizumab Cohort A1 | 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. |
|
|
| Primary | Number of Participants With Laboratory Clinical Chemistry Abnormalities Meeting the Criteria for Potential Clinical Concern (PCC) | 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. | All Subjects Population | Posted | Number | Participants | Up to Month 24 (Long term follow-up) |
|
|
|
| Primary | Number of Participants With Laboratory Hematology Abnormalities Meeting the Criteria for PCC | 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. | All Subjects Population | Posted | Number | Participants | Upto Month 24 (Long term follow-up) |
|
|
|
| Primary | Number of Participants With Laboratory Urinalysis Abnormalities Meeting the Criteria for PCC | 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. | All Subjects Population | Posted | Number | Participants | Up to Month 24 (Long term follow-up) |
|
|
|
| Primary | Number of Participants With Thyroid Function Assessment, Hormone and Glucose Assay Abnormalities Meeting the Criteria for PCC | 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. | All Subjects Population | Posted | Number | Participants | Up to Week 24 |
|
|
|
| Primary | Number of Participants With Vital Signs Abnormalities Meeting the Criteria for PCC | 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. | All Subjects Population | Posted | Number | Participants | Up to Month 24 (Long term follow-up) |
|
|
|
| Primary | Number of Participants With Electrocardiogram (ECG) Abnormalities Meeting the Criteria for PCC | 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. | All Subjects Population | Posted | Number | Participants | Screening (Day -35 to Day -1) |
|
|
|
| Primary | Number of Participants With an Epstein Barr Virus (EBV) Viral Load Abnormalities Meeting the Criteria for PCC | 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. | All Subjects Population | Posted | Number | Participants | Week 2 to Week 12 |
|
|
|
| Primary | Individual Absolute Circulating Peripheral T Lymphocytes (T-cells), CD4+ and CD8+ Subset Counts | 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. | All Subjects Population. No participants were available for analysis because of early termination of study. | Posted | Up to Week 24 |
|
|
| Primary | Percentage of Circulating Peripheral T-cells, CD4+ and CD8+ Subset Counts | 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. | All Subjects Population. No participants were available for analysis because of early termination of study. | Posted | Up to Week 24 |
|
|
| Primary | Assessment of CD3/T-cell Receptor (TCR) Complex Saturation and Modulation | 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. | All Subjects Population. No participants were available for analysis because of early termination of study. | Posted | Up to Week 24 |
|
|
| Secondary | 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 | 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. | All Subjects Population. No participants were available for analysis because of early termination of study. | Posted | Baseline (Day 1, pre dose) and Week 12 |
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| Secondary | Change From Baseline for Participant-reported Health Related Quality of Life (QoL) Questionnaires of Short Form 36 ( SF-36) and Graves Ophthalmopathy (GO) QoL | 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. | All Subjects Population. No participants were available for analysis because of early termination of study. | Posted | Baseline (Day 1, pre dose) to Week 24 |
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| Secondary | Change From Baseline Measurement of Orbital Volume as Measured by Computed Tomography (CT) Scan | 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. | All Subjects Population. No participants were available for analysis because of early termination of study. | Posted | Baseline (Screening), Week 12 and Week 24 |
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| Secondary | Assessment of Anti-otelixizumab Antibodies | 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. | All Subjects Population. No participants were available for analysis because of early termination of study. | Posted | Up to Month 12 |
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| Secondary | Assessment of Circulating Cytokines of Interleukin 6 (IL6), IL10, Interferon Gamma (IFNγ) and Tumor Necrosis Factor Alpha (TNFα) up to 2 Weeks | 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. | All Subjects Population. No participants were available for analysis because of early termination of study. | Posted | Up to Week 2 |
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| Secondary | Assessment of Exploratory Biomarkers | 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. | All Subjects Population. No participants were available for analysis because of early termination of study. | Posted | Up to Week 24 |
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| Secondary | Assessment of Exploratory Biomarkers of Ribonucleic Acid (RNA) Transcription Analysis of Peripheral Blood | 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. | All Subjects Population. No participants were available for analysis because of early termination of study. | Posted | Up to Week 24 |
|
|
| 0 |
| 2 |
| 0 |
| 2 |
| 2 |
| 2 |
| Foreign body sensation in eyes | Eye disorders | MedDRA | Systematic Assessment |
|
| Hot Flush | Vascular disorders | MedDRA | Systematic Assessment |
|
| Eye Pain | Eye disorders | MedDRA | Systematic Assessment |
|
| Vertigo positional | Ear and labyrinth disorders | MedDRA | Systematic Assessment |
|
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.
| D009916 |
| Orbital Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D006042 | Goiter |
| D013959 | Thyroid Diseases |
| D004700 | Endocrine System Diseases |
| D006980 | Hyperthyroidism |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D013256 |
| Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |