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Thyroid Eye DiseasePhase 3OPTICNCT03298867

Treatment of Graves' Orbitopathy (Thyroid Eye Disease) to Reduce Proptosis With Teprotumumab Infusions in a Randomized, Placebo-Controlled, Clinical Study

A Phase 3 study testing Teprotumumab in people with Thyroid Eye Disease and Graves' Orbitopathy, run by Amgen at 14 sites in 3 countries.

Completed

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

Official record
Search all trials

Trial summary

The overall objective is to investigate the efficacy, tolerability, and safety of teprotumumab (a fully human monoclonal antibody [mAb] inhibitor of the insulin-like growth factor-1 receptor [IGF-1R]) administered once every 3 weeks (q3W) for 21 weeks with a final assessment at Week 24, in comparison to placebo, in… Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
Thyroid Eye Disease, Graves' Orbitopathy
What is being tested?
Teprotumumab
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
83 participants
Where
14 sitesin 3 countries
Study dates
4 Oct 2017to 30 Nov 2020
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.
  • Male or female participant between the ages of 18 and 80 years, inclusive, at Screening.
  • Clinical diagnosis of Graves' disease associated with active TED with a Clinical Activity Score (CAS) ≥ 4 (on the 7-item scale) for the most severely affected eye at Screening and Baseline.
  • Moderate-to-severe active TED (not sight-threatening but has an appreciable impact on daily life), usually associated with one or more of the following: lid retraction ≥ 2 mm, moderate or severe soft tissue involvement, exophthalmos ≥ 3 mm above normal for race and gender, and/or inconstant or constant diplopia.
  • Onset of active TED symptoms (as determined by participant records) within 9 months prior to Baseline.
  • Participants 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 Screening. 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.
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  • Does not require immediate surgical ophthalmological intervention and is not planning corrective surgery/irradiation during the course of the study.
  • Alanine aminotransferase (ALT) or AST ≤ 3 times the upper limit of normal (ULN) or serum creatine <1.5 times the ULN according to age at Screening.
  • Diabetic participants must have well-controlled stable disease (defined as HbA1C < 9.0% with no new diabetic medication [oral or insulin] or more than a 10% change in the dose of a currently prescribed diabetic medication within 60 days prior to Screening).
  • Women of childbearing potential (including those with an onset of menopause <2 years prior to Screening, non-therapy-induced amenorrhea for <12 months prior to Screening, or not surgically sterile [absence of ovaries and/or uterus]) must have a negative serum pregnancy test at Screening and negative urine pregnancy tests at all protocol-specified timepoints (i.e., prior to each dose and through Week 48 of the Follow-Up Period); participants who are sexually active with a non-vasectomized male partner must agree to use 2 reliable forms of contraception during the trial, one of which is recommended to be hormonal, such as an oral contraceptive. Hormonal contraception must be started at least one full cycle prior to Baseline and continue for 180 days after the last dose of study drug. Highly effective contraceptive methods (with a failure rate less than 1% per year) when used consistently and correctly, includes implants, injectables, combined oral contraceptives, intrauterine devices (IUDs), sexual abstinence or vasectomized partner.
  • Male participants must be surgically sterile or, if sexually active with a female partner of childbearing potential, must agree to use barrier contraceptive method from Screening through 180 days after the last dose of study drug.
  • Participant is willing and able to comply with the study protocol and evaluations for the duration of the study.

Who cannot join

  • Decreased best corrected visual acuity due to optic neuropathy as defined by a decrease in vision of 2 lines on the Snellen chart, new visual field defect, or color defect secondary to optic nerve involvement within the last 6 months.
  • Corneal decompensation unresponsive to medical management.
  • Decrease in CAS of ≥ 2 points in the study eye between Screening and Baseline.
  • Decrease in proptosis of ≥ 2 mm in the study eye between Screening and Baseline.
  • Previous orbital irradiation or surgery for TED.
  • Any steroid use (intravenous [IV] or oral) with a cumulative dose equivalent to ≥ 1 g of methylprednisolone for the treatment of TED. Previous steroid use (IV or oral) with a cumulative dose of <1 g methylprednisolone or equivalent for the treatment of TED and previous use of steroid eye drops is allowed if the corticosteroid was discontinued at least 4 weeks prior to Screening.
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  • Corticosteroid use for conditions other than TED within 4 weeks prior to Screening (topical steroids for dermatological conditions and inhaled steroids are allowed).
  • Selenium and biotin must be discontinued 3 weeks prior to Screening and must not be restarted during the clinical trial; however, taking a multivitamin that includes selenium and/or biotin is allowed.
  • Any previous treatment with rituximab or tocilizumab. Use of any other non-steroid immunosuppressive agent within 3 months prior to Screening.
  • Use of an investigational agent for any condition within 60 days prior to Screening or anticipated use during the course of the trial.
  • Identified pre-existing ophthalmic disease that, in the judgment of the Investigator, would preclude study participation or complicate interpretation of study results.
  • Bleeding diathesis that in the judgment of the Investigator would preclude inclusion in the clinical trial.
  • Malignant condition in the past 12 months (except successfully treated basal/squamous cell carcinoma of the skin).
  • Pregnant or lactating women.
  • Current drug or alcohol abuse, or history of either within the previous 2 years, in the opinion of the Investigator or as reported by the participant.
  • Biopsy-proven or clinically suspected inflammatory bowel disease.
  • Known hypersensitivity to any of the components of teprotumumab or prior hypersensitivity reactions to mAbs.
  • Any other condition that, in the opinion of the Investigator, would preclude inclusion in the study.
  • Previous enrollment in this study or participation in a prior teprotumumab clinical trial.
  • Human immunodeficiency virus (HIV), hepatitis C or hepatitis B infections.

Trial locations and contacts

14 sites in 3 countries.

14 sites in 3 countries

United States9 sites

  • Kellogg Eye Center at University of Michigan

    Ann Arbor, Michigan, 48105

  • Macro, Llc

    Beverly Hills, California, 90212

  • The Lennar Foundation Medical

    Coral Gables, Florida, 33146

  • Eye Wellness Center

    Houston, Texas, 77005

  • Cedars-Sinai Medical Center

    Los Angeles, California, 90078

  • Hamilton Eye Institute at University of Tennessee Health Science Center

    Memphis, Tennessee, 38163

  • Bascom Palmer Eye Institute

    Miami, Florida, 33136

  • Medical College of Wisconsin, The Eye Institute

    Milwaukee, Wisconsin, 53226

  • Casey Eye Institute at Oregon Health and Science University

    Portland, Oregon, 97239

Other trials in United States

Italy3 sites

  • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

    Milan, 20122

  • University of Pisa, Department of Clinical and Experimental Medicine

    Pisa, 56100

  • University of Pisa,Department of Clinical and Experimental Medicine, Endocrinology Unit

    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: A Phase 3, Randomized, Double-Masked, Placebo-Controlled, Parallel-Group, Multicenter Study Evaluating Teprotumumab (HZN-001) Treatment in Subjects With Active Thyroid Eye Disease

The overall objective is to investigate the efficacy, tolerability, and safety of teprotumumab (a fully human monoclonal antibody [mAb] inhibitor of the insulin-like growth factor-1 receptor [IGF-1R]) administered once every 3 weeks (q3W) for 21 weeks with a final assessment at Week 24, in comparison to placebo, in the treatment of participants with moderate-to-severe active thyroid eye disease (TED).

Read the detailed description

This is a randomized, double-masked, placebo-controlled, parallel-group, multicenter study. Approximately 76 participants (38/group) who meet the study eligibility criteria will be randomized on Day 1 in a 1:1 ratio (stratified by tobacco use status) to receive 8 infusions of teprotumumab or placebo q3W. All participants will enter a 24-week double-masked Treatment Period, during which study drug will be infused on Day 1 (Baseline), and Weeks 3, 6, 9, 12, 15, 18, and 21 (with a final visit at Week 24). All study drug dosing will be performed at the clinic under the supervision of clinic staff. On each dosing day, scheduled assessments (except for adverse event [AE] and concomitant medication use monitoring, which will be monitored throughout the clinic visit) will be completed prior to study drug dosing.

At the end of the double-masked Treatment Period (Week 24), participants who are proptosis non-responders (study eye has < 2 mm decrease in proptosis) will be eligible to enter an open-label extension study in which participants receive 8 infusions of teprotumumab in an open-label fashion.

At Week 24, proptosis responders, as well as non-responders who choose not to enroll in the open-label extension study, will enter a 48-week Follow-Up Period, during which study drug will not be administered and clinic visits are scheduled for Weeks 28, 36, 48, 60, and 72. Participants who are considered responders at Week 24 but who meet criteria for re-treatment due to relapse during the Follow-Up Period may enroll in the open-label extension study.

Participants who complete the Week 72 Visit will be contacted 6 and 12 months later via phone or email by research staff to enquire if any treatment for TED has been received since last study contact.

Study acquired from Horizon in 2024.

Being tested
Teprotumumab, Placebo
Keywords
Proptosis, Human monoclonal antibody, insulin-like growth factor-1 receptor, Thyroid-Associated Ophthalmopathy, Autoimmune Thyroid Disease, Graves' Orbitopathy
Medical subject headings
Graves Ophthalmopathy, Exophthalmos

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).

  • PlaceboOther

    Also called Saline solution

    Placebo will consist of normal saline (0.9% NaCl) solution and will be administered in 100 mL or 250 mL infusion bags, as would be appropriate, per weight-based dosing volumes (100 mL infusion bags for doses up to 1800 mg and 250 mL infusion bags for doses > 1800 mg).

Study groups in NCT03298867
Study groupRoleWhat they receive
Teprotumumab 20 mg/kgActive comparatorApproximately 38 participants will receive 8 infusions of teprotumumab q3W for a total of 21 weeks. Teprotumumab 10 mg/kg will be administered on Day 1 and teprotumumab 20 mg/kg will be administered q3W for the remaining 7 infusions.
Receives: Biological: Teprotumumab
PlaceboPlacebo comparatorApproximately 38 participants will receive 8 infusions of placebo q3W for a total of 21 weeks.
Receives: Other: Placebo

What is being measured

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

  1. Percentage of Participants Who Were Proptosis Responders at Week 24

    Proptosis responders were defined as participants with a ≥2 mm reduction from Baseline in proptosis in the study eye, without deterioration (≥2 mm increase) of proptosis in the fellow eye at Week 24.

    Measured: Week 24

Secondary outcomes (5)

  1. Percentage of Participants Who Were Overall Responders at Week 24

    Overall responders were defined as participants with a ≥2 mm reduction in proptosis AND a ≥2 point reduction in Clinical Activity Score (CAS) from Baseline in the study eye, without deterioration (≥2 mm increase in proptosis or ≥2 point increase in CAS) in the fellow eye at Week 24.

    The CAS is a 7-item description of clinical activity, including: 1. Spontaneous orbital pain; 2. Gaze evoked orbital pain; 3. Eyelid swelling that is considered to be due to active (inflammatory phase) thyroid eye disease/ Graves' Ophthalmopathy or Orbitopathy (TED/GO); 4. Eyelid erythema; 5. Conjunctival redness that is considered to be due to active (inflammatory phase) TED/GO (ignore "equivocal" redness); 6. Chemosis; 7. Inflammation of caruncle or plica. Each item is scored (1=present; 0=absent) and scores for each item are summed for total score of 0 (no clinical activity) to 7 (most clinical activity).

    Measured: Week 24

  2. Percentage of Participants Who Were CAS Categorical Responders at Week 24 (Study Eye)

    CAS categorical responders were defined as participants with a reduction to a CAS of 0 or 1 (no or minimal inflammatory symptoms) in study eye.

    The CAS is a 7-item description of clinical activity, including: 1. Spontaneous orbital pain; 2. Gaze evoked orbital pain; 3. Eyelid swelling that is considered to be due to active (inflammatory phase) thyroid eye disease/ Graves' Ophthalmopathy or Orbitopathy (TED/GO); 4. Eyelid erythema; 5. Conjunctival redness that is considered to be due to active (inflammatory phase) TED/GO (ignore "equivocal" redness); 6. Chemosis; 7. Inflammation of caruncle or plica. Each item is scored (1=present; 0=absent) and scores for each item are summed for total score of 0 (no inflammatory symptoms) to 7 (most inflammatory symptoms).

    Measured: Week 24

  3. Change From Baseline in Proptosis to Week 24 (Study Eye)

    Measured: Baseline, up to Week 24

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

    Diplopia responders were defined as participants with Baseline diplopia Subjective Diplopia Score grade >0 in the study eye who had a reduction of ≥1 grade with no corresponding deterioration (≥1 grade worsening) in the fellow eye at Week 24. Denominator is the number of subjects with diplopia at Baseline.

    The Subjective Diplopia Score is a clinical measure of diplopia severity on a grade scale of 0 to 3: 0=no diplopia; 1=intermittent (diplopia in primary position of gaze, when tired or when first awakening); 2=inconstant (diplopia at extremes of gaze); 3=constant (continuous diplopia in primary or reading position).

    Measured: Week 24

  5. Change From Baseline in the Graves' Ophthalmopathy Quality of Life (GO-QoL) Questionnaire Overall Score to 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 subjects on (i) their daily physical activity as it relates to visual function, and (ii) psychosocial functioning. The range of the GO-QoL overall transformed scores is 0 to 100, where higher values correspond to better quality of life.

    Measured: Baseline, up to 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 posted2 Oct 2017
  2. Study start4 Oct 2017
  3. Primary completion13 Feb 2019
  4. Study completion30 Nov 2020

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
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
83 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03298867
Sponsor's protocol ID
HZNP-TEP-301
Other IDs
2017-002763-18, 2017
Acronym
OPTIC
Status last verified
Jun 2024
First submitted
27 Sep 2017
Last updated
11 Jul 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

  • Douglas RS, Kahaly GJ, Patel A, Sile S, Thompson EHZ, Perdok R, Fleming JC, Fowler BT, Marcocci C, Marino M, Antonelli A, Dailey R, Harris GJ, Eckstein A, Schiffman J, Tang R, Nelson C, Salvi M, Wester S, Sherman JW, Vescio T, Holt RJ, Smith TJ. Teprotumumab for the Treatment of Active Thyroid Eye Disease. N Engl J Med. 2020 Jan 23;382(4):341-352. doi: 10.1056/NEJMoa1910434.

    PubMed 31971679

  • Jain AP, Gellada N, Ugradar S, Kumar A, Kahaly G, Douglas R. Teprotumumab reduces extraocular muscle and orbital fat volume in thyroid eye disease. Br J Ophthalmol. 2022 Feb;106(2):165-171. doi: 10.1136/bjophthalmol-2020-317806. Epub 2020 Nov 10.

    PubMed 33172865

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Teprotumumab in people with Thyroid Eye Disease and Graves' Orbitopathy, run by Amgen at 14 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 12 inclusion and 20 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 11 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 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. Some participants in this study may receive a placebo. 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 10 Mar 2020). 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 Who Were Proptosis Responders at Week 24 (time frame: 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 NCT03298867, which also lists 2 linked publications.

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 11 Jul 2024.

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