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Thyroid Eye DiseasePhase 3OPTIC-XNCT03461211

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

A Phase 3 study testing Teprotumumab in people with Thyroid Eye Disease, run by Amgen at 13 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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… Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
Thyroid Eye Disease
What is being tested?
Teprotumumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
51 participants
Where
13 sitesin 3 countries
Study dates
16 Apr 2018to 17 Feb 2021
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Written informed consent.
  • Completed the 24-week double-masked Treatment Period in Study HZNP-TEP-301 (NCT03298867).
  • Proptosis non-responder (< 2 mm reduction in proptosis in the study eye) at Week 24 of Study HZNP-TEP-301 OR proptosis responder at Week 24 who relapses during the Follow-Up Period of Study HZNP-TEP-301.
  • Participant must be euthyroid with the baseline disease under control, or have mild hypo- or hyperthyroidism (defined as free thyroxine [FT4] and free triiodothyronine [FT3] levels < 50% above or below the normal limits) at the most recent clinic visit. Every effort should be made to correct the mild hypo- or hyperthyroidism promptly and to maintain the euthyroid state for the full duration of the clinical trial.
  • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤3 times the upper limit of normal (ULN) or serum creatinine <1.5 times the upper limit of normal (ULN; according to age) at the most recent clinic visit.
  • Diabetic participants must have well-controlled disease (defined as hemoglobin A1C [HbA1c] < 9.0% at most recent clinic visit).
Show all 11Show fewer
  • Does not require immediate surgical ophthalmological intervention and is not planning corrective surgery/irradiation during the course of the study.
  • Women of childbearing potential must have a negative urine pregnancy test at Baseline/Day 1. Participants who are sexually active with a non-vasectomized male partner must agree to use 2 reliable forms of contraception during the trial and continue for 180 days after the last dose of study drug. One of the 2 forms of contraception is recommended to be hormonal, such as an oral contraceptive. Hormonal contraception must be in use for at least one full cycle prior to Baseline. Highly effective contraceptive methods (with a failure rate less than 1% per year), when used consistently and correctly, includes implants, injectables, combined oral contraceptives, some intrauterine devices (IUDs), sexual abstinence or vasectomised partner.
  • Male participants must be surgically sterile or, if sexually active with a female partner of childbearing potential, must agree to use a barrier contraceptive method from Baseline through 180 days after the last dose of study drug.
  • Participant is willing and able to comply with the prescribed treatment protocol and evaluations for the duration of the study.
  • Has not received any treatment for TED since Week 24 of the of the HZNP-TEP-301 study.

Who cannot join

  • Participants will be ineligible if, in the opinion of the Investigator, they are unlikely to comply with the study protocol or have a concomitant disease or condition that could interfere with the conduct of the study or potentially put the participant at unacceptable risk.
  • The exclusion criteria (except those related to screening) of protocol HZNP-TEP-301(NCT03298867) also apply to this open-label extension study.

Trial locations and contacts

13 sites in 3 countries.

13 sites in 3 countries

United States8 sites

  • Kellogg Eye Center at University of Michigan

    Ann Arbor, Michigan, 48105

  • Macro, Llc

    Beverly Hills, California, 90212

  • Eye Wellness Center

    Houston, Texas, 77005

  • Cedars-Sinai Medical Center

    Los Angeles, California, 90078

  • Hamilton Eye Institute at University of Tennessee Health

    Memphis, Tennessee, 38163

  • Bascom Palmer Eye Institute

    Miami, Florida, 33135

  • Medical College of Wisconsin, The Eye Institute

    Milwaukee, Wisconsin, 53226

  • Casey Eye Institute at Oregon Health and Science

    Portland, Oregon, 97239

Other trials in United States

Italy3 sites

  • Fondazione IRCCS Ca Granda Ospedale Maggiore

    Milan, 20122

  • University of Pisa, Department of Clinical and Experimental Medicine

    Pisa, 56100

  • Azienda Ospedaliero Universitaria Pisana

    Pisa, 56124

Other trials in Italy

Germany2 sites

  • University Hospital Essen, Department of Ophthalmology

    Essen, 45147

  • Johannes Gutenberg University Medical Center

    Mainz, 55131

Other trials in Germany

About this study

Official title: Multicenter, Safety and Efficacy, Open-Label Extension Study Evaluating Teprotumumab (HZN-001) Treatment in Subjects With Thyroid Eye Disease

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.

Read the detailed description

This is a multi-center, open-label extension study of HZNP-TEP-301 (NCT03298867) examining the safety and efficacy of teprotumumab in the treatment of TED in adult participants. Participants who complete the 24-week double-masked Treatment Period in Study HZNP-TEP-301 and are proptosis non-responders or are proptosis responders at Week 24 but meet the criteria for re-treatment due to relapse during the Follow-Up Period of HZNP-TEP-301 will be eligible for enrollment.

All participants who choose to participate will receive 8 infusions of teprotumumab (10 mg/kg for the first infusion followed by 20 mg/kg for the remaining 7 infusions) in an open-label fashion. The Baseline (Day 1) Visit of this extension study will occur within 14 days after the final visit of Study HZNP-TEP-301 (Week 24 for proptosis non-responders and up to Week 72 for participants who relapse). During the open-label Treatment Period, study drug infusions are scheduled for Day 1 (Baseline), and Weeks 3, 6, 9, 12, 15, 18, and 21, (with the final visit at Week 24). After completion of the Treatment Period, subjects who were proptosis non-responders in Study HZNP-TEP-301 will enter a 24-week Follow-Up Period during which study drug will not be administered and clinic visits are scheduled for 1, 3, and 6 months (Visits Month 7, 9, and 12) after the Week 24 visit. Subjects will be contacted 6 and 12 months later by phone or email to enquire if any treatment for TED had been received since the last study contact.

Participants who relapse during the Follow-Up Period of HZNP-TEP-301 and choose to enter this extension study will not participate in the Follow-Up Period of this study but will be contacted by phone or email 6 and 12 months after the Week 24 visit.

Study acquired from Horizon in 2024.

Being tested
Teprotumumab
Medical subject headings
Graves Ophthalmopathy

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TeprotumumabBiological

    Also called HZN-001

    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).

Study groups in NCT03461211
Study groupRoleWhat they receive
TeprotumumabExperimentalEight 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.
Receives: Biological: Teprotumumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Baseline, Week 24

Secondary outcomes (4)

  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.

    Measured: 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.

    Measured: 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.

    Measured: 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.

    Measured: Study Baseline, Week 24

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Mar 2018
  2. Study start16 Apr 2018
  3. Primary completion8 Jun 2020
  4. Study completion17 Feb 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
51 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03461211
Sponsor's protocol ID
HZNP-TEP-302
Other IDs
2017-002713-58, 2017
Acronym
OPTIC-X
Status last verified
Jun 2024
First submitted
5 Mar 2018
Last updated
28 Jun 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.

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

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Teprotumumab in people with Thyroid Eye Disease, run by Amgen at 13 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in United States, Italy, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Jul 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 (time frame: Baseline, Week 24). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03461211, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jun 2024.

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