Treatment of Graves' Orbitopathy to Reduce Proptosis With Teprotumumab Infusions in an Open-Label Clinical Extension Study

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• Graves Ophthalmopathy 198

Graves Ophthalmopathy

198 studies on the registry are indexed under Graves Ophthalmopathy; 60 are open to participants now.

This study's enrollment of 51 is below the median of 64 across 147 interventional studies indexed under Graves Ophthalmopathy.

Lead sponsor

Amgen is the lead sponsor of 1,044 studies on the registry; 51 are open to participants now.

Of its 246 completed or terminated interventional studies of FDA-regulated products, 164 (67%) have results posted.

Study arms

• Experimental
  Teprotumumab

  Eight infusions of teprotumumab every 3 weeks (q3W) for a total of 21 weeks: teprotumumab 10 mg/kg administered on Day 1 and teprotumumab 20 mg/kg administered q3W for the remaining 7 infusions.

  Biological: Teprotumumab

Interventions

• BiologicalTeprotumumab

  Teprotumumab is a fully human anti-IGF-1R mAb. Teprotumumab will be provided in single-dose 20 mL glass vials as a freeze-dried powder. Each vial of teprotumumab must be reconstituted with 10 mL of water for injection. Reconstituted teprotumumab solution must be further diluted in 0.9% (w/v) sodium chloride (NaCl) solution prior to administration. Teprotumumab will be administered in 100 mL or 250 mL infusion bags (100 mL infusion bags for doses up to 1800 mg and 250 mL infusion bags for doses \> 1800 mg).

  Also known as: HZN-001

Primary outcomes

1. Percentage of Participants With a ≥ 2 mm Reduction From Baseline in the Study Eye Without Deterioration of Proptosis in the Fellow Eye at Week 24

   Proptosis responders were defined as participants with a ≥ 2 mm reduction from study baseline in proptosis in the study eye, without deterioration (≥ 2 mm increase) of proptosis in the fellow eye at Week 24. Participants missing Week 24 values were considered non-responders, aside from those with missing data related to the COVID-19 pandemic.

   Time frame: Baseline, Week 24

Secondary outcomes

1. Percentage of Participants With a European Group on Graves' Ophthalmopathy (EUGOGO) Amended Clinical Activity Score (CAS) Total Score of 0 or 1 in the Study Eye at Week 24

   CAS responders were defined as participants with a reduction to a CAS of 0 or 1 (no or minimal inflammatory symptoms) as a categorical response variable at Week 24. The 7-item CAS assigns 1 point for each of the following items present in the study eye: spontaneous orbital pain; gaze evoked orbital pain; eyelid swelling that is considered to be due to active (inflammatory phase) thyroid eye disease/Graves' ophthalmopathy (TED/GO); eyelid erythema; conjunctival redness that is considered to be due to active (inflammatory phase) TED/GO (ignore "equivocal" redness); chemosis; inflammation of caruncle or plica. The sum of these points is the total score (0 to 7), with higher scores indicating worse symptoms.

   Time frame: Week 24

2. Change in Proptosis From Baseline to Week 24

   Mean change from study baseline to Week 24 in proptosis measurement (mm) in the study eye at Week 24.

   Time frame: Study Baseline, Week 24

3. Percentage of Participants Who Were Diplopia Responders at Week 24

   Diplopia responders were defined as participants with 1 grade or greater reduction in diplopia score in the study eye without worsening by at least 1 grade in the fellow eye at Week 24. The subjective diplopia score (0=no diplopia; 1=intermittent, i.e. diplopia in primary position of gaze, when tired or when first awakening; 2=inconstant, i.e. diplopia at extremes of gaze; 3=constant, i.e. continuous diplopia in primary or reading position) was recorded for each eye. A participant was considered to have diplopia if a score \> 0 is observed in the study eye at study baseline.

   Time frame: Week 24

4. Mean Change From Baseline to Week 24 in the Graves' Ophthalmopathy Quality of Life (GO-QoL) Questionnaire Overall Score

   The GO-QoL is a 16-item self-administered questionnaire divided into 2 subsets and used to assess the perceived effects of TED by the participants on (i) their daily physical activity as it relates to visual function, and (ii) psychosocial functioning. The sum of the scores from each set of 8 questions was calculated and transformed to a scale from 0 (worst) to 100 (best) - one for visual function (VF), one for appearance (A) and one for the overall combined (VF + A) score. Scores were transformed as follows: Transformed score = \[(sum of each score - number of completed items) / (2 \* number of completed items)\] \* 100. The "overall combined (VF + A) score" is also 0 to 100, with higher scores indicating a better outcome.

   Time frame: Study Baseline, Week 24

Baseline characteristics

Publications

• Xin Y, Xu F, Gao Y, Bhatt N, Chamberlain J, Sile S, Hammel S, Holt RJ, Ramanathan S. Pharmacokinetics and Exposure-Response Relationship of Teprotumumab, an Insulin-Like Growth Factor-1 Receptor-Blocking Antibody, in Thyroid Eye Disease. Clin Pharmacokinet. 2021 Aug;60(8):1029-1040. doi: 10.1007/s40262-021-01003-3. Epub 2021 Mar 26. PubMed 33768488 ↗

Related links

• Related Info ↗

Study documents

• Study protocol · Jan 31, 2019
• Statistical analysis plan · Jun 17, 2020

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.

Supporting information: Study protocol, Statistical analysis plan, Informed consent form, Clinical study report

Time frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.

Access criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.

Data sharing details ↗ · www.amgen.com