A Study to Evaluate the Pharmacodynamics, Pharmacokinetics, Safety, and Efficacy of UB-221 IV Infusion as an add-on Therapy in Patients With Chronic Spontaneous Urticaria

NCT05298215 | Unknown Phase 2 DMC

• 1 other identifier: UBP-A236-IgE
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase II, double-blind, randomized, parallel group, placebo-controlled study to evaluate the pharmacodynamics, pharmacokinetics, efficacy, and safety of 2-dose UB-221 IV infusion as an add-on therapy in patients with chronic spontaneous urticaria. The study will be conducted at multiple study centers in Taiwan. Approximate 25 eligible subjects will be randomized into two UB-221 (5 \&10 mg/kg) and one placebo (saline) cohorts in a ratio of 2:2:1. The study consists of a pre-screening period (Day -42 to -29), a screening period (Day -28 to -1), a dose 1 period (Day 0 to 83), and a dose 2 period (Day 84 to 196).

Conditions

Chronic Spontaneous Urticaria

Outcome Measures

Primary Outcomes (1)

• Change in serum free IgE level from baseline over time

  To evaluate the extent of reduction and duration of suppression of serum free IgE level upon q12w (once-every-12-weeks) treatment with UB-221

  Day 0 to 83

Secondary Outcomes (1)

• Time to complete response (UAS7=0) after the 1st dose of UB-221 administration.

  Day 84 to 196

Study Arms (3)

5 mg/kg UB-221

EXPERIMENTAL

Total of 2 doses on Day 0 (week 1) and 84 (Week 12), respectively, by intravenous (IV) infusion.

Biological: UB-221

10 mg/kg UB-221

EXPERIMENTAL

Total of 2 doses on Day 0 (week 1) and 84 (Week 12), respectively, by intravenous (IV) infusion.

Biological: UB-221

Placebo

PLACEBO COMPARATOR

sterile saline solution (0.9% NaCl) for intravenous (IV) infusion

Other: sterile saline solution

Interventions

UB-221 BIOLOGICAL

UB-221 is a recombinant humanized IgG1 monoclonal antibody with neutralizing capability against soluble human IgE and CD23-bound IgE for the treatment of allergic diseases. The activity of UB-221 is directly through the high-affinity binding with soluble and membrane bound IgE. The neutralization of soluble IgE will desensitize the activation of mast cells and basophils by inhibiting IgE cross-linking and down-regulation of FcεRI (high affinity IgE receptor) expression on those cells. The binding to CD23-bound IgE may inhibit IgE synthesis by stabilization of membrane-bound CD23 on B lymphocytes.

Also known as: recombinant humanized IgG1 monoclonal antibody

10 mg/kg UB-221; 5 mg/kg UB-221

sterile saline solution OTHER

sterile saline solution (0.9% NaCl) for intravenous (IV) infusion

Placebo

Eligibility Criteria

• Age: 20 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects with age between 20 to 75 years old (inclusive).
• Subjects who are able and willing to provide the informed consent.
• Male subjects with body weight of 50 kilogram (kg) or above; female subjects with body weight of 45 kilogram (kg) or above.
• Subjects with moderate-to-severe chronic spontaneous urticaria (CSU) (with or without urticaria dermographism when testing for dermographism) refractory to H1-antihistamine (H1-AH) at approved dose or increased dose alone or in combination with H2-antihistamine (H2-AH) and/or leukotriene receptor antagonist (LTRA) at the time of randomization (Day 0), as defined by All of the following:
• CSU diagnosis for ≥ 6 months.
• The presence of itch and hives for ≥ 6 consecutive weeks at any time prior to enrollment despite current use of non-sedating H1-AH (up to 4-fold of the approved dosage) or in combination with H2-AH, and/or LTRA treatment during this time period.
• UAS7 score ≥ 16 and HSS7 ≥ 8 during 7 days prior to randomization (Day 0).
• In-clinic UAS ≥ 4 on at least one of the screening visit days or Day 0.
• Patients must have been on H1-AH at approved or increased doses (up to 4-fold) alone or in combination with H2-AH and/or LTRA for treatment of CSU for at least 3 consecutive days immediately prior to the screening visit and must have documented current use on the initial screening visit day.
• Both male and female subjects of childbearing potential must agree to use 2 medically accepted methods of contraception (e.g., barrier contraceptives \[male condom, female condom, or diaphragm with a spermicidal gel\], hormonal contraceptives \[implants, injectables, combination oral contraceptives, transdermal patches, or contraceptive rings\], and intrauterine devices) during the course of the study with their partners (excluding women who are not of childbearing potential and men who have been sterilized).
• \*Female subjects who had bilateral insertion of Essure® implants (or analogous) for at least 6 months prior to the screening visit; bilateral tubal ligation, hysterectomy or bilateral oophorectomy; or postmenopausal status with amenorrhea (no menstruation) for at least 2 years prior to the screening visit, are considered as non-childbearing potential by the investigator's judgment.
• Females must have a negative serum pregnancy test at the screening visit and negative urine pregnancy test prior to each study drug administration.

You may not qualify if:

• History of significant diseases (other than CSU) or major clinical conditions by the investigator's judgment, such as auto-immune disease or psychiatric and behavioral conditions from which the investigator considers the subject is not suitable to participate in this study.
• History of anaphylaxis to food, medications, or other causes.
• History of severe eosinophilia (eosinophil counts \> 5000 /uL).
• History of drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, stevens-Johnson syndrome (SJS), or toxic epidermal necrolysis (TEN).
• History of serious cardiovascular or cerebrovascular diseases by the investigator's judgment within 1 year prior to the screening visit.
• Subject who is taking beta-blocker at time of screening or is suggested to take beta-blocker during the study period.
• Any other skin disease associated with chronic itching that might confound the study evaluations and results (e.g., atopic dermatitis, bullous pemphigoid, dermatitis herpetiformis, senile pruritus, etc.).
• Having clearly defined underlying etiology for chronic urticaria other than CSU. This includes the following:
• Patients have inducible urticaria forms impacting their daily symptoms in a relevant way, such as but not limited to urticaria factitia, cold-, heat-, solar-, pressure-, delayed pressure-, aquagenic-, cholinergic-, or contact-urticaria.
• Diseases with possible symptoms of urticaria or angioedema such as urticaria vasculitis, erythema multiforme, cutaneous mastocytosis (urticaria pigmentosa), and hereditary or acquired angioedema (e.g., due to C1 inhibitor deficiency)
• Use of any of the following medications: a) systemic corticosteroids (such as prednisolone), b) immunomodulators (including but not limited to azathioprine, mycophenolate, cyclophosphamide, chlorambucil, methotrexate, tacrolimus, cyclosporine). Subjects can be enrolled when they discontinued these medications for at least 4 weeks prior to the screening visit.
• Use of doxepin (oral) within 14 days prior to the screening visit.
• Treatment with any investigational agent (except investigational anti-IgE mAb) within 60 days or 5 half-lives (whichever is longer) prior to the screening visit.
• Prior experience with other investigational anti-IgE Ab drug such as QGE031 (ligelizumab) or FB825.
• Previous exposure to Xolair® (omalizumab) or UB-221 within 26 weeks prior to the screening visit.

Sponsors & Collaborators

• United BioPharma: lead

Study Sites (1)

National Taiwan University Hospital

Taipei, Taiwan

RECRUITING

MeSH Terms

Conditions

Chronic Urticaria

Condition Hierarchy (Ancestors)

Urticaria; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Chia Yu Chu, MD

  Dermatologist

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Linda Shih

CONTACT

+886-3-6684800; linda.shih@unitedbiopharma.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 17, 2022
• First Posted: March 28, 2022
• Study Start: October 5, 2022
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2023
• Last Updated: October 7, 2022

Record last verified: 2022-10

Locations

TW (1)