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NCT03461211: OPTIC-X

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

Completed Phase 3 Results posted Last updated 28 June 2024
What this trial tests

Phase 3 trial testing Teprotumumab in Thyroid Eye Disease in 51 participants. Completed in 17 February 2021.

Timeline
16 April 2018
Primary endpoint
8 June 2020
17 February 2021

Quick facts

Lead sponsorAmgen
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment51
Start date16 April 2018
Primary completion8 June 2020
Estimated completion17 February 2021
Sites13 locations across Italy, United States, Germany

Drugs / interventions tested

Conditions studied

Sponsor

Amgen — full company profile →

Who can join

Adults 18 to 80, any sex, with Thyroid Eye Disease. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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 Primary · Baseline, 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.

GroupValue95% CI
Teprotumumab (OPTIC Placebo)89.2
Teprotumumab (OPTIC Teprotumumab)53.8
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 Secondary · 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 car

GroupValue95% CI
Teprotumumab (OPTIC Placebo)65.6
Teprotumumab (OPTIC Teprotumumab)36.4
Change in Proptosis From Baseline to Week 24 Secondary · Study Baseline, Week 24

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

GroupValue95% CI
Teprotumumab (OPTIC Placebo)-3.47± 1.732
Teprotumumab (OPTIC Teprotumumab)-1.77± 1.126
Percentage of Participants Who Were Diplopia Responders at Week 24 Secondary · 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.

GroupValue95% CI
Teprotumumab (OPTIC Placebo)60.9
Teprotumumab (OPTIC Teprotumumab)75.0
Mean Change From Baseline to Week 24 in the Graves' Ophthalmopathy Quality of Life (GO-QoL) Questionnaire Overall Score Secondary · Study Baseline, Week 24

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

GroupValue95% CI
Teprotumumab (OPTIC Placebo)13.39± 17.890
Teprotumumab (OPTIC Teprotumumab)14.73± 11.777

Adverse events — posted to ClinicalTrials.gov

Time frame: All-Cause Mortality and Serious Adverse Events (AEs): from informed consent through 30 days after study discontinuation. Mean days on study was 332.9 and 218.8 for Teprotumumab (OPTIC Placebo) and Teprotumumab (OPTIC Teprotumumab) arms, respectively.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Treatment Period: Teprotumumab (OPTIC Placebo)
Serious: 0/37 (0%)
Deaths: 0/37
Treatment Period: Teprotumumab (OPTIC Teprotumumab)
Serious: 1/14 (7%)
Deaths: 0/14
Follow-Up Period: No Treatment (OPTIC Placebo)
Serious: 0/36 (0%)
Deaths: 0/36
Follow-Up Period: No Treatment (OPTIC Teprotumumab)
Serious: 0/4 (0%)
Deaths: 0/4

Serious adverse events (1 terms)

ReactionSystemTreatment Period: Teprotum…Treatment Period: Teprotum…Follow-Up Period: No Treat…Follow-Up Period: No Treat…
Cerebral HaemorrhageNervous system disorders
Other adverse events (124 terms — click to expand)

ReactionSystemTreatment Period: Teprotum…Treatment Period: Teprotum…Follow-Up Period: No Treat…Follow-Up Period: No Treat…
Muscle SpasmsMusculoskeletal and connective tissue disorders
DiarrhoeaGastrointestinal disorders
FatigueGeneral disorders
DysgeusiaNervous system disorders
AlopeciaSkin and subcutaneous tissue disorders
Dry SkinSkin and subcutaneous tissue disorders
OnychoclasisSkin and subcutaneous tissue disorders
Ear DiscomfortEar and labyrinth disorders
Abdominal Pain UpperGastrointestinal disorders
InfluenzaInfections and infestations
Urinary Tract InfectionInfections and infestations
Pain In ExtremityMusculoskeletal and connective tissue disorders
DepressionPsychiatric disorders
RhinorrhoeaRespiratory, thoracic and mediastinal disorders
ThrombocytopeniaBlood and lymphatic system disorders
HypoacusisEar and labyrinth disorders
TinnitusEar and labyrinth disorders
VertigoEar and labyrinth disorders
Dry EyeEye disorders
Aphthous UlcerGastrointestinal disorders
SinusitisInfections and infestations
ArthralgiaMusculoskeletal and connective tissue disorders
Back PainMusculoskeletal and connective tissue disorders
Disturbance In AttentionNervous system disorders
HeadacheNervous system disorders
TremorNervous system disorders
AmenorrhoeaReproductive system and breast disorders
Nasal DrynessRespiratory, thoracic and mediastinal disorders
RashSkin and subcutaneous tissue disorders
Rash PruriticSkin and subcutaneous tissue disorders
LeukopeniaBlood and lymphatic system disorders
PalpitationsCardiac disorders
AutophonyEar and labyrinth disorders
AstigmatismEye disorders
Eye IrritationEye disorders
Eye PainEye disorders
KeratitisEye disorders
Lenticular OpacitiesEye disorders
Ocular DiscomfortEye disorders
Punctate KeratitisEye disorders

Most-reported serious reactions: Cerebral Haemorrhage.

Data from ClinicalTrials.gov NCT03461211 adverse events section.

Sponsor's own description

The overall objective is to evaluate the safety and efficacy of teprotumumab in the treatment of thyroid eye disease (TED) in participants who participated in the lead-in study HZNP-TEP-301 (NCT03298867; OPTIC) and who were either proptosis non-responders at Week 24 of HZNP-TEP-301 or were proptosis responders at Week 24 but met the criteria for re-treatment due to relapse during the Follow-Up Period of HZNP-TEP-301.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Antibodies to watch in 2019.
    Kaplon H, Reichert JM. · · 2019 · cited 324× · PMID 30516432 · DOI 10.1080/19420862.2018.1556465
  2. 2021 update on thyroid-associated ophthalmopathy.
    Neag EJ, Smith TJ. · · 2022 · cited 79× · PMID 34417736 · DOI 10.1007/s40618-021-01663-9
  3. Updates on the understanding and management of thyroid eye disease.
    Men CJ, Kossler AL, Wester ST. · · 2021 · cited 41× · PMID 34263138 · DOI 10.1177/25158414211027760
  4. Pharmacokinetics and Exposure-Response Relationship of Teprotumumab, an Insulin-Like Growth Factor-1 Receptor-Blocking Antibody, in Thyroid Eye Disease.
    Xin Y, Xu F, Gao Y, Bhatt N, et al · · 2021 · cited 17× · PMID 33768488 · DOI 10.1007/s40262-021-01003-3
  5. Teprotumumab: a novel therapeutic monoclonal antibody for thyroid-associated ophthalmopathy.
    Slentz DH, Nelson CC, Smith TJ. · · 2020 · cited 17× · PMID 32429706 · DOI 10.1080/13543784.2020.1772752
  6. Novel Approaches for Immunosuppression in Graves' Hyperthyroidism and Associated Orbitopathy.
    Lee ACH, Kahaly GJ. · · 2020 · cited 15× · PMID 33511082 · DOI 10.1159/000508789
  7. Lessons Learned from Targeting IGF-I Receptor in Thyroid-Associated Ophthalmopathy.
    Janssen JAMJL, Smith TJ. · · 2021 · cited 12× · PMID 33673340 · DOI 10.3390/cells10020383
  8. Teprotumumab: a disease modifying treatment for graves' orbitopathy.
    Ting M, Ezra DG. · · 2020 · cited 11× · PMID 32636936 · DOI 10.1186/s13044-020-00086-7

Verify or expand the search:

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Other Amgen trials

Trials by the same sponsor.

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