Study of ZB001 in Chinese Patients With Thyroid Eye Disease
Study Details
Study Description
Brief Summary
The investigational drug, ZB001 is a humanized IgG1κ monoclonal antibody targeting human IGF-1R. The study is designed to evaluate the efficacy, safety, tolerability, and pharmacokinetics（PK）/pharmacodynamics (PD) profile of ZB001 in Chinese patients with Thyroid Eye Disease.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: ZB001 for injection Treat different dose cohorts with four intravenous injections of ZB001 |
Drug: ZB001 for injection
Dose Cohort1 (3 mg/kg) ZB001 four IV injections
Drug: ZB001 for injection
Dose Cohort2 (10 mg/kg) ZB001 four IV injections
Drug: ZB001 for injection
Dose Cohort3 (20 mg/kg) ZB001 four IV injections
|
Outcome Measures
Primary Outcome Measures
- Number of participants with Adverse events (AEs), serious adverse events (SAEs), and laboratory assessments as assessed by CTCAE v5.0 [through study completion, up to 99 days]
- Proptosis responder rate at Week 6 and Week 12, defined as the proportion of patients with reduction of proptosis by ≥ 2 mm from baseline as measured by Hertel exophthalmometry [At week6 and week 12]
Secondary Outcome Measures
- Change from baseline in the study eye at Week 6 and Week 12 of Measurement of proptosis by magnetic resonance imaging (MRI) [At week6 and week 12]
- Change from baseline in the study eye at Week 6 and Week 12 of Volume of orbital fat as determined by MRI [At week6 and week 12]
- Change from baseline in the study eye at Week 6 and Week 12 of Volume of extraocular muscles as determined by MRI [At week6 and week 12]
- Change from baseline in the study eye at Week 6 and Week 12 of Facial fat volume as determined by MRI [At week6 and week 12]
- Change from baseline in the study eye at Week 6 and Week 12 of Digital and manual measurement of lid retraction [At week6 and week 12]
- Change from baseline in the study eye at Week 6 and Week 12 of Strabismus measurement [At week6 and week 12]
- Change from baseline in the study eye at Week 6 and Week 12 of Subjective diplopia score. The range of score is from 0-3. The lower score means the better outcome. [At week6 and week 12]
- Change from baseline in the study eye at Week 6 and Week 12 of Best corrected visual acuity (BCVA) [At week6 and week 12]
- Change from baseline in the study eye at Week 6 and Week 12 of Intraocular pressure (IOP) [At week6 and week 12]
- Change from baseline in the study eye at Week 6 and Week 12 of Clinical Activity Score (CAS) . The range of score is from 0-7. The lower score means the better outcome [At week6 and week 12]
- Change from baseline in the study eye at Week 6 and Week 12 of Graves'Orbitopathy - Quality of Life (GO-QoL) combined score. The range of score is from 0-100. The higher change of quality of life means the better outcome. [At week6 and week 12]
- Change from baseline in the study eye at Week 6 and Week 12 of GO-QOL activity subscale. The range of score is from 0-100. The higher change of quality of life means the better outcome. [At week6 and week 12]
- Change from baseline in the study eye at Week 6 and Week 12 of GO-QoL appearance subscale. The range of score is from 0-100.The higher change of quality of life means the better outcome. [At week6 and week 12]
- Serum ZB001 antidrug antibody (ADA) titers [Before and after drug administration, performed according to the protocol visit time specified in the plan, up to 99 days]
antidrug antibody (ADA) titers of ZB001
- Serum IGF-1 concentrations in the blood over time [Before and after drug administration, performed according to the protocol visit time specified in the plan, up to 99 days]
- Maximum observed concentration (Cmax) [Before and after drug administration, performed according to the protocol visit time specified in the plan, up to 99 days]
Pharmacokinetics
- Time to measured peak concentration (Tmax) [Before and after drug administration, performed according to the protocol visit time specified in the plan, up to 99 days]
Pharmacokinetics
- Area under the concentration-time curve from time 0 to the last timepoint with measurable concentration (AUClast) [Before and after drug administration, performed according to the protocol visit time specified in the plan, up to 99 days]
Pharmacokinetics
- Area under the concentration-time curve extrapolated to infinity (AUCinf) [Before and after drug administration, performed according to the protocol visit time specified in the plan, up to 99 days]
Pharmacokinetics
- Area under the concentration-time curve over a dosing interval (AUCtau) [Before and after drug administration, performed according to the protocol visit time specified in the plan, up to 99 days]
Pharmacokinetics
- half life (t1/2) [Before and after drug administration, performed according to the protocol visit time specified in the plan, up to 99 days]
Pharmacokinetics
- Systemic clearance (CL) [Before and after drug administration, performed according to the protocol visit time specified in the plan, up to 99 days]
Pharmacokinetics
- Steady State Volume of Distribution (Vss) [Before and after drug administration, performed according to the protocol visit time specified in the plan, up to 99 days]
Pharmacokinetics
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Adult male or female, 18 years of age or older
-
A clinical diagnosis of Graves'orbitopathy associated with TED with a CAS of ≥ 4 on the 7-item scale for the study eye
-
Moderate to severe (i.e., an appreciable impact on daily living) active TED: proptosis ≥ 18.6 mm, or progressive proptosis (≥ 3 mm higher than the patient's previous proptosis according to the investigator) and at least one of the following: lid retraction of ≥ 2 mm, moderate or severe soft tissue involvement (conjunctiva congestion or edema or periorbital congestion or edema), and/or periodic or constant diplopia
-
Documented evidence of ocular symptoms or signs associated with TED that began within 1 year before study screening
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Euthyroid, or have only mild hyper- or hypothyroidism, defined as free thyroxine (FT4) and free triiodothyronine (FT3) levels in the range of 0.5-1.5 times of the normal limits at Screening. Every effort must be made to correct any mild hypo- or hyperthyroidism promptly and maintain a euthyroid state for the entire duration of the study. Thyroidectomy is NOT an exclusion
-
Women of childbearing potential (including those having been postmenopausal for < 1 year, with amenorrhea for < 1 year or not surgically sterilized) must have a negative serum pregnancy test result at Screening; such patients must agree to practice effective contraception as described in the relevant protocol section (Section 9.2 Contraception and Pregnancy) for at least one full menstrual cycle before the first dose of study drug and continue to do so for 100 days after the last dose of study drug
-
Male patients must have been surgically sterilized for at least 6 weeks or agree to practice effective contraception as described in the relevant protocol section (Section 9.2 Contraception and Pregnancy) from prior to the first dose of study drug through 100 days after the last dose of study drug
Exclusion Criteria:
-
Decreased BCVA in the study eye, defined as ≥ 0.2 as measured using the standard logarithmic visual acuity chart, due to optic neuropathy, new visual field defect, or color defect secondary to optic nerve involvement within the previous 6 months
-
Corneal decompensation in the study eye unresponsive to medical management
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A decrease in CAS of ≥ 2 points between screening assessment and Day -1
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A decrease in proptosis of ≥ 2 mm in the study eye between screening assessment and Day -1
-
Had previous orbital irradiation or surgery in the study eye for TED
-
Known history of clinically significant ear pathology, ear surgery, or hearing impairment
-
Inflammatory bowel disease (e.g., biopsy-proven or clinical evidence of inflammatory bowel disease)
-
Cumulative glucocorticoid use equivalent to ≥ 1 g of methylprednisolone for the treatment of TED (previous treatment with a lower cumulative dose of glucocorticoid or eyedrop of glucocorticoid is permitted providing such treatment was discontinued ≥ 6 weeks before screening)
-
Used oral corticosteroids at any dose for conditions other than TED within 4 weeks before screening (topical use permitted)
-
Pregnancy or breastfeeding
-
Smoker (≥ 5 cigarettes per day) or former smoker (≥ 5 cigarettes per day) having quitted less than 6 months prior to enrollment in the study
-
Any vaccination planned during the study
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Peking Union Medical College Hospital | Beijing | Beijing | China | 100730 |
Sponsors and Collaborators
- Zenas BioPharma (USA), LLC
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ZB001-01-002