A Phase 3, Randomized, Double-masked, Placebo-controlled, Parallel-group Multicenter Trial to Evaluate the Efficacy and Safety of HZN-001 in Treating Japanese Participants with Chronic (Inactive) Thyroid Eye Disease
A trial to investigate the efficacy, safety and tolerability of an intravenous infusion of HZN-001 compared with placebo in treating male and female Japanese participants at least 18 years of age with chronic (inactive) thyroid eye disease
Inamori Ayami
CMIC Co., Ltd.
1-1-1, Shibaura, Minato-ku, Tokyo
+81-90-8722-5166
ClinicalTrialInformation@cmic.co.jp
Inamori Ayami
CMIC Co., Ltd.
1-1-1, Shibaura, Minato-ku, Tokyo
+81-90-8722-5166
ClinicalTrialInformation@cmic.co.jp
Recruiting
Mar. 31, 2023
Mar. 29, 2023
105
Interventional
randomized controlled trial
double blind
placebo control
parallel assignment
treatment purpose
1. Participant has provided written informed consent.
2. Participant is male or female at least 18 years old at Screening.
3. Participant has clinical diagnosis of stable cTED with a CAS <= 2 in both eyes for at least 1 year prior to Screening, AND Participant has an initial diagnosis of TED >= 2 years but < 10 years prior to Screening, or all of the following:
a. No progression in proptosis for at least 1 year prior to Screening
b. If participant has history of diplopia due to TED, no progression in diplopia for at least 1 year prior to Screening
c. No new inflammatory TED symptoms for at least 1 year prior to Screening.
4. Participant has CAS <= 2 at the Screening and Baseline Visits.
5. Participant has proptosis >= 18 mm at the Screening and Baseline Visits.
6. Participants must be euthyroid with the participant's baseline disease under control or have mild hypo- or hyperthyroidism (defined as free thyroxine and free triiodothyronine 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 trial.
7. Participant does not require immediate surgical ophthalmological intervention and is not planning corrective surgery/irradiation during the course of the trial.
8. Diabetic participants must have glycated hemoglobin (HbA1c) < 8.0% at Screening.
9. Participants with a history of IBD, ulcerative colitis or Crohn's disease must be in clinical remission for at least 3 months, with no history of bowel surgery within 6 months prior to Screening and no planned surgery during the trial. Concomitant stable therapies for IBD without modifications in the 3 months prior to Screening are allowed.
10. 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 time points (ie, prior to each dose and throughout participation in the trial); participants who are sexually active with a non-vasectomized male partner must agree to use 2 reliable forms of contraception during the trial, 1 of which is recommended to be hormonal, such as an oral contraceptive. Hormonal contraception must be started at least 1 full cycle prior to Baseline and continue for 180 days after the last dose of IP. Highly effective contraceptive methods (failure rate < 1% per year), when used consistently and correctly, include implants, injectables, combination oral contraceptives, some intrauterine devices, bilateral tubal occlusion, sexual abstinence and vasectomized partner. Abstinence should only be used as a contraceptive method if it is in line with the participant's usual and preferred lifestyle and that periodic abstinence [eg, calendar, ovulation, symptothermal, post-ovulation methods] is not an acceptable method of contraception. Periodic abstinence, withdrawal (coitus interruptus) or spermicides only are not acceptable methods of contraception.
11. Participant is willing and able to comply with the prescribed treatment protocol and evaluations for the duration of the trial.
1. Participant has decreased best-corrected visual acuity due to optic neuropathy, defined by a decrease in vision of 2 lines on the Snellen chart (or equivalent), new visual field defect or color defect secondary to optic nerve involvement within the last 6 months.
2. Participant has corneal decompensation unresponsive to medical management in the study eye.
3. Participant has decrease in proptosis of >= 2 mm in the study eye between Screening and Baseline.
4. Participant had prior orbital irradiation or orbital decompression in the study eye.
5. Participant had prior strabismus surgery.
6. Participant had botulinum toxin (Botox) injection around eyes within 12 months prior to Day 1.
7. Participant has alanine aminotransferase or aspartate aminotransferase >= 3 x the upper limit of normal or estimated glomerular filtration rate <= 30 mL/min/1.73 m2 at Screening.
8. Participant used any systemic use of any steroid (intravenous injection or oral), or intraorbital injection, or steroid eye drops for the treatment of TED or other conditions within 3 weeks prior to Screening. Such steroids cannot be initiated during the trial. Exceptions include local administration (excluding periocular), e.g., topical, intraarticular, and inhaled steroids, as well as steroids used to treat infusion reactions.
9. Participant received any treatment with rituximab (Rituxan or MabThera) within 12 months prior to the first infusion of IP or tocilizumab (Actemra or Roactemra) within 6 months prior to the first infusion of IP or had used any other non-steroid immunosuppressive agent within 3 months prior to the first infusion of IP.
10. Participant received any previous treatment with HZN-001, including previous enrollment in this trial or participation in a prior HZN-001 trial.
11. Participant received treatment with any monoclonal antibody within 3 months prior to Screening.
12. Participant used selenium within 3 weeks prior to Screening. Selenium must not be restarted during the trial; however, taking a multivitamin that includes selenium (less than 100 microg daily) is allowed.
13. Participant has pre-existing ophthalmic disease that, in the judgment of the Investigator, would preclude trial participation or complicate interpretation of trial results.
14. Participant used an investigational agent for any condition within 60 days or 5 half-lives, whichever is longer, prior to Screening or anticipates use during the course of the trial.
15. Participant had a malignant condition in the past 12 months (except successfully treated basal/squamous cell carcinoma of the skin or cervical cancer in situ).
16. Participant is a pregnant or lactating woman.
17. Participant has 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.
18. Participant has known hypersensitivity to any of the components of HZN-001 or prior hypersensitivity reactions to monoclonal antibodies.
19. Participant has poorly controlled human immunodeficiency virus infection or participant has hepatitis C or hepatitis B infections with high viral load. Participants may be eligible if no acute/active hepatitis is indicated by liver enzyme levels and by antigen/antibody status.
20. Participant has any other condition that, in the opinion of the Investigator, would preclude inclusion in the trial.
18age old over
No limit
Both
Chronic (Inactive) Thyroid Eye Disease
Approximately 105 participants who meet the trial eligibility criteria will be randomized on Day 1 in a 2:1 ratio (stratified by tobacco use status and presence of diplopia at Baseline) to receive 8 infusions of HZN-001 (Generic name: teprotumumab, Brand name (USA): TEPEZZA) (10 mg/kg for the first infusion and 20 mg/kg for the remaining 7 infusions) or placebo once every 3 weeks (q3W). All participants will enter a 24-week Double-masked Treatment Period, during which IP will be infused on Day 1 (Baseline) and Weeks 3, 6, 9, 12, 15, 18 and 21 (with a final visit at Week 24 of the 24-week Treatment Period).
Proptosis responder rate (defined as the percentage of participants with a >= 2-mm reduction from Baseline in proptosis in the study eye without deterioration of proptosis [increase >= 2 mm] in the fellow eye) at Week 24
