Thyroid Associated OphthalmopathiesPhase 2NCT01868997
Teprotumumab (RV 001) Treatment in Patients With Active Thyroid Eye Disease
A Phase 2 study testing teprotumumab and normal saline in people with Thyroid Associated Ophthalmopathies and Thyroid-Associated Ophthalmopathy, run by Amgen at 15 sites in 4 countries.
Trial summary
The primary objective of this study is to investigate the efficacy, safety, and tolerability of RV 001 (teprotumumab), a fully human anti-IGF1R antibody, administered q3W for 6 months, in comparison to placebo, in the treatment of participants suffering from active TED. "Funding Source - FDA OOPD" Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Thyroid Associated Ophthalmopathies, Thyroid-Associated Ophthalmopathy
- What is being tested?
- teprotumumab and normal saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 88 participants
- Where
- 15 sitesin 4 countries
- Study dates
- Jul 2013to 22 Feb 2017
- Phase
- Phase 2
- 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Clinical diagnosis of Graves' disease associated with active TED and a clinical activity score of ≥ 4
- Fewer than 9 months from onset of TED
- No previous medical or surgical treatment, excluding local supportive measures and oral steroids if the maximum cumulative dose is less than 1000 mg methylprednisolone or equivalent with at least 6 weeks between last administration of oral steroids and randomization
- Euthyroid or with mild hypo or hyperthyroidism defined as free thyroxine (FT4) and free triiodothyronine (FT3) levels less than 50% above or below the normal limits (every effort should be made to correct the mild hypo- or hyperthyroidism promptly)
Who cannot join
- Optic neuropathy
- Corneal decompensation unresponsive to medical management
- Oral or IV steroid treatment for any non-TED reason in the preceding 3 months
- Poorly controlled diabetes
- Platelets < 100 x 10^9/L
- Hemoglobin concentration > 2 g/dL below the lower limit of normal
Trial locations and contacts
15 sites in 4 countries.
15 sites in 4 countries
United States11 sites
Kellogg Eye Center at University of Michigan
Ann Arbor, Michigan, 48105
Emory University Department of Ophthalmology
Atlanta, Georgia, 30322
University of Denver
Aurora, Colorado, 80045
Eye Wellness Center
Houston, Texas, 77005
University of Iowa Hospitals and Clinics, Department of Ophthalmology
Iowa City, Iowa, 52242
Jules Stein Eye Institute at UCLA
Los Angeles, California, 90095
Hamilton Eye Institute at University of Tennessee
Memphis, Tennessee, 38163
Medical College of Wisconsin, The Eye Institute
Milwaukee, Wisconsin, 53226
University of Nebraska Medical Center Department of Ophthalmology
Omaha, Nebraska, 68198
Casey Eye Institute at Oregon Health and Science University
Portland, Oregon, 97239
Washington University Department of Ophthalmology
St Louis, Missouri, 63110
Italy2 sites
Fondazione Ca' Granda Ospedale Policlinico Graves GO Center
Milan, 20122
University of Pisa, Azienda Ospedaliera
Pisa, 56100
About this study
Official title: A Multicenter, Double-Masked, Placebo-Controlled, Efficacy And Safety Study Of RV 001, An Insulin-Like Growth Factor-1 Receptor (IGF-1R) Antagonist Antibody (Fully Human), Administered Every 3 Weeks (q3W) By Intravenous (IV) Infusion In Patients Suffering From Active Thyroid Eye Disease (TED)
The primary objective of this study is to investigate the efficacy, safety, and tolerability of RV 001 (teprotumumab), a fully human anti-IGF1R antibody, administered q3W for 6 months, in comparison to placebo, in the treatment of participants suffering from active TED.
"Funding Source - FDA OOPD"
Read the detailed description
Study with completed results acquired from Horizon in 2024.
- Being tested
- teprotumumab, normal saline
- Keywords
- Thyroid Eye Disease, Graves Orbitopathy, Thyroid Associated, Ophthalmopathy
- Medical subject headings
- Graves Ophthalmopathy, Eye Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
teprotumumabDrug
Also called RV 001, HZN-001
normal salineDrug
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | A placebo infusion (normal saline) administered q3W by IV infusion over a period of 24 weeks for a total of 8 infusions. Receives: Drug: normal saline |
| Teprotumumab | Experimental | Teprotumumab administered q3W by IV infusion over a period of 24 weeks for a total of 8 infusions. All participants start treatment at a dose of 10 mg/kg. At Week 3, the dose is escalated to 20 mg/kg and kept constant for the remainder of the study. Receives: Drug: teprotumumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Responder Status at Week 24
Number of participants classified as responders and non-responders at Week 24. Responders were defined as participants with a reduction in clinical activity score (CAS, see Outcome Measure 4 description for details) of ≥ 2 points, and a reduction in proptosis (amount of protrusion of the eye from the orbital rim) of ≥ 2 mm in the study eye, and no deterioration (increase in CAS of ≥ 2 points or increase in proptosis of ≥ 2 mm) in the non-study eye. Participants who had no assessment at 24 weeks were considered non-responders.
Measured: Week 24
Secondary outcomes (5)
Overall Average Change From Baseline in Graves' Ophthalmopathy Quality of Life (GO-QOL) Scale - Overall to Week 24 (Mixed-Model Repeated Measures [MMRM])
The GO-QOL is a 16-item self-administered questionnaire used to assess the perceived effects of thyroid eye disorder (TED) by the participants on their daily physical and psychosocial functioning. Two subscales of the 16-question GO-QOL have been defined: Visual Functioning and Appearance, with 8 questions comprising each subscale. The transformed overall score is the sum of scores from all 16 questions to a scale of 0 (worst health) to 100 (best health).
Measured: Baseline to Week 24
Overall Average Change From Baseline in Proptosis of the Study Eye to Week 24 (MMRM)
Proptosis is the amount of protrusion of the eye from the orbital rim. Measurements were recorded using the Hertel exophthalmometer. Participants with a decrease ≥ 2 mm were considered improving, those with an increase or decrease < 2 mm were considered remaining stable, and those with an increase ≥ 2 mm were considered worsening.
Measured: Baseline to Week 24
Overall Average Change From Baseline in CAS to Week 24 (MMRM)
The 7-item European Group on Graves' Ophthalmopathy (EUGOGO) amended CAS was used to evaluate clinical activity. For each of the following items, one point is given: spontaneous orbital pain, gaze evoked orbital pain, eyelid swelling that is considered to be due to active (inflammatory phase) Graves' ophthalmopathy (GO), eyelid erythema, conjunctival redness that is considered to be due to active (inflammatory phase) GO, chemosis, and inflammation of caruncle or plica. The sum of these points is the total score, with 0 indicating no clinical activity and 7 indicating the most severe clinical activity.
Measured: Baseline to Week 24
Overall Average Change From Baseline in GO-QOL Scale - Visual Functioning to Week 24 (MMRM)
The GO-QOL is a 16-item self-administered questionnaire used to assess the perceived effects of TED by the participants on their daily physical and psychosocial functioning. Two subscales of the 16-question GO-QOL have been defined: Visual Functioning and Appearance, with 8 questions comprising each subscale. Transformed Visual Functioning score is the sum of scores from following 8 questions to a scale of 0 (worst health) to 100 (best health): bicycling, driving, moving around the house, walking outdoors, reading, watching television (TV), hobby or pastime, feel hindered.
Measured: Baseline to Week 24
Overall Average Change From Baseline in GO-QOL Scale - Appearance to Week 24 (MMRM)
The GO-QOL is a 16-item self-administered questionnaire used to assess the perceived effects of TED by the participants on their daily physical and psychosocial functioning. Two subscales of the 16-question GO-QOL have been defined: Visual Functioning and Appearance, with 8 questions comprising each subscale. Transformed Appearance score is the sum of scores from the following 8 questions to a scale of 0 (worst health) to 100 (best health): feel appearance has changed, feel being stared at, feel people react unpleasantly, influence on self-confidence, feel socially isolated, influence on making friends, appear less often on photos, try to mask changes in appearance.
Measured: Baseline to Week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jun 2013 (estimated)
- Study startJul 2013
- Primary completionMar 2016
- Study completion22 Feb 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Thyroid Associated OphthalmopathiesStudies of the same condition, open and under way.
- More trials run by AmgenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 88 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amgen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- MD, Study director, Amgen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01868997
- Sponsor's protocol ID
- TED01RV
- Other IDs
- FD004792-01A1, 2014-000113-31, 2014
- Status last verified
- Dec 2024
- First submitted
- 2 May 2013
- Last updated
- 17 Dec 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Publications
Smith TJ, Kahaly GJ, Ezra DG, Fleming JC, Dailey RA, Tang RA, Harris GJ, Antonelli A, Salvi M, Goldberg RA, Gigantelli JW, Couch SM, Shriver EM, Hayek BR, Hink EM, Woodward RM, Gabriel K, Magni G, Douglas RS. Teprotumumab for Thyroid-Associated Ophthalmopathy. N Engl J Med. 2017 May 4;376(18):1748-1761. doi: 10.1056/NEJMoa1614949.
PubMed 28467880Xin 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 33768488Wang Y, Smith TJ. Current concepts in the molecular pathogenesis of thyroid-associated ophthalmopathy. Invest Ophthalmol Vis Sci. 2014 Mar 20;55(3):1735-48. doi: 10.1167/iovs.14-14002.
PubMed 24651704
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Double-Masked, Placebo-Controlled, Efficacy And Safety Study Of RV 001, An Insulin-Like Growth Factor-1 Receptor (IGF-1R) Antagonist Antibody (Fully Human), Administered Every 3 Weeks (q3W) By Intravenous (IV) Infusion In Patients Suffering From Active Thyroid Eye Disease (TED)
- ClinicalTrials.gov ID
- NCT01868997
- Acronym / sponsor ID
- TED01RV
- Keywords
- Thyroid Eye Disease, Graves Orbitopathy, Thyroid Associated, Ophthalmopathy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 88 participants (actual)
- Lead sponsor
- AmgenIndustry (pharma, biotech, devices)
- Study start
- Jul 2013 (actual)
- Primary completion
- Mar 2016 (actual)
- Study completion
- 22 Feb 2017 (actual)
- First posted
- 5 Jun 2013 (estimated)
- Results
- Posted 30 Aug 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of this study is to investigate the efficacy, safety, and tolerability of RV 001 (teprotumumab), a fully human anti-IGF1R antibody, administered q3W for 6 months, in comparison to placebo, in the treatment of participants suffering from active TED.
"Funding Source - FDA OOPD"
Detailed description
Study with completed results acquired from Horizon in 2024.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: normal salineA placebo infusion (normal saline) administered q3W by IV infusion over a period of 24 weeks for a total of 8 infusions. |
| Teprotumumab | Experimental | Drug: teprotumumabTeprotumumab administered q3W by IV infusion over a period of 24 weeks for a total of 8 infusions. All participants start treatment at a dose of 10 mg/kg. At Week 3, the dose is escalated to 20 mg/kg and kept constant for the remainder of the study. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Clinical diagnosis of Graves' disease associated with active TED and a clinical activity score of ≥ 4
- Fewer than 9 months from onset of TED
- No previous medical or surgical treatment, excluding local supportive measures and oral steroids if the maximum cumulative dose is less than 1000 mg methylprednisolone or equivalent with at least 6 weeks between last administration of oral steroids and randomization
- Euthyroid or with mild hypo or hyperthyroidism defined as free thyroxine (FT4) and free triiodothyronine (FT3) levels less than 50% above or below the normal limits (every effort should be made to correct the mild hypo- or hyperthyroidism promptly)
Key exclusion criteria (6 listed)
- Optic neuropathy
- Corneal decompensation unresponsive to medical management
- Oral or IV steroid treatment for any non-TED reason in the preceding 3 months
- Poorly controlled diabetes
- Platelets < 100 x 10^9/L
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| teprotumumabAlso: RV 001, HZN-001 | Drug | Teprotumumab |
| normal saline | Drug | Placebo |
Primary outcome
Responder Status at Week 24
Time frame: Week 24
Number of participants classified as responders and non-responders at Week 24. Responders were defined as participants with a reduction in clinical activity score (CAS, see Outcome Measure 4 description for details) of ≥ 2 points, and a reduction in proptosis (amount of protrusion of the eye from the orbital rim) of ≥ 2 mm in the study eye, and no deterioration (increase in CAS of ≥ 2 points or increase in proptosis of ≥ 2 mm) in the non-study eye. Participants who had no assessment at 24 weeks were considered non-responders.
5 secondary outcomes
Overall Average Change From Baseline in Graves' Ophthalmopathy Quality of Life (GO-QOL) Scale - Overall to Week 24 (Mixed-Model Repeated Measures [MMRM])
Time frame: Baseline to Week 24
Overall Average Change From Baseline in Proptosis of the Study Eye to Week 24 (MMRM)
Time frame: Baseline to Week 24
Overall Average Change From Baseline in CAS to Week 24 (MMRM)
Time frame: Baseline to Week 24
Overall Average Change From Baseline in GO-QOL Scale - Visual Functioning to Week 24 (MMRM)
Time frame: Baseline to Week 24
Overall Average Change From Baseline in GO-QOL Scale - Appearance to Week 24 (MMRM)
Time frame: Baseline to Week 24
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Dec 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 28467880Smith TJ, Kahaly GJ, Ezra DG, Fleming JC, Dailey RA, Tang RA, Harris GJ, Antonelli A, Salvi M, Goldberg RA, Gigantelli JW, Couch SM, Shriver EM, Hayek BR, Hink EM, Woodward RM, Gabriel K, Magni G, Douglas RS. Teprotumumab for Thyroid-Associated Ophthalmopathy. N Engl J Med. 2017 May 4;376(18):1748-1761. doi: 10.1056/NEJMoa1614949.
- Derived from this study: PubMed 33768488Xin 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.
- Derived from this study: PubMed 24651704Wang Y, Smith TJ. Current concepts in the molecular pathogenesis of thyroid-associated ophthalmopathy. Invest Ophthalmol Vis Sci. 2014 Mar 20;55(3):1735-48. doi: 10.1167/iovs.14-14002.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
MD study director
Amgen
15 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing teprotumumab and normal saline in people with Thyroid Associated Ophthalmopathies and Thyroid-Associated Ophthalmopathy, run by Amgen at 15 sites in 4 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 4 inclusion and 6 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 17 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in United States, Italy, Germany, United Kingdom. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 30 Aug 2017). 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?
Responder Status 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 NCT01868997, which also lists 3 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 17 Dec 2024.