A Phase 1 Study of Cizutamig in IgE Mediated Diseases

This is a Phase 1b, open-label study evaluating the pharmacodynamics, safety, tolerability, pharmacokinetics, and immunogenicity of cizutamig in IgE Mediated Diseases.

• Cizutamig (Biological): cizutamig will be dosed SC according to the assigned cohort

Primary outcomes

• To evaluate the ability of cizutamig to reduce IgE levels [Baseline to Week 12]: Change from baseline in serum IgE

Secondary outcomes

• Incidence and severity of treatment-emergent adverse events through end of study [Baseline to Week 24]
• PK parameters: Cmax [Baseline to 24 Weeks]
• PK parameters: Tmax [Baseline to Week 24]
• PK parameters: AUC [Baseline to 24 Weeks]
• PK Parameter: CL [Baseline to 24 Weeks]
• PK Parameters: Vd [Baseline to 24 Weeks]
• PK Parameters: t1/2 [Baseline to 24 Weeks]
• Anti-drug antibodies (ADAs) [Baseline to 24 Weeks]
• Changes in body temperature [Baseline to 24 Weeks]
• Changes to blood pressure [Baseline to 24 Weeks]: systolic and diastolic
• Changes in heart rate [Baseline to 24 Weeks]
• Changes to respiratory rate [Baseline to 24 Weeks]
• Changes to pulse oximetry [Baseline to 24 Weeks]
• Changes in ECG parameters: QRS interval [Baseline to 24 Weeks]
• Changes in ECG parameters: PR interval [Baseline to 24 Weeks]
• Changes in ECG parameters: QTcB [Baseline to 24 Weeks]
• Changes in ECG parameters: QTcF [Baseline to 24 Weeks]
• Changes in ECG parameters: QT interval [Baseline to 24 Weeks]
• Changes in ECG parameters: RR [Baseline to 24 Weeks]
• Changes from baseline in safety laboratory assessments through end of study: serum chemistry [Baseline to 24 Weeks]
• Changes from baseline in Red Blood Cell count [Baseline to 24 Weeks]
• Changes from baseline in White Blood Cell count [Baseline to 24 Weeks]
• Changes from baseline in Platelets [Baseline to 24 Weeks]
• Changes from baseline in Hematocrit [Baseline to 24 Weeks]
• Changes from baseline in Hemoglobin [Baseline to 24 Weeks]
• Frequency and percentage of anti-drug antibodies (ADAs) [Baseline to 24 Weeks]

Sex: All, ages: 18 Years to 65 Years

Inclusion Criteria:

1. Patient meets at least one of the following:

   1. History of documented (skin prick test, in vitro testing, or food challenge), ongoing, IgE-mediated allergy to food (eg, peanut, hazelnut, walnut, cashew, milk, egg/egg white, soy, wheat, sesame, cod, salmon, tuna, lobster, crab and/or shrimp) with Screening total IgE ≥ 400 IU/mL
   2. Diagnosis of chronic rhinosinusitis with Screening total IgE > ULN
   3. Diagnosis of allergic rhinitis with Screening total IgE > ULN
   4. Diagnosis of asthma and classified as well controlled per 2024 Global Initiative for Asthma guidelines with Screening total IgE > ULN
   5. Diagnosis of chronic spontaneous urticaria with symptoms (eg, wheals or angioedema) for at least 6 weeks any time prior to screening and Screening total IgE > ULN
   6. Diagnosis of atopic dermatitis that has been present for at least 6 months before the screening visit and with Screening total IgE > ULN
2. Agree to the use of highly effective contraception

Exclusion Criteria:

1. Elevated IgE levels for reasons other than the IgE mediated diseases
2. Planned ingestion of food items to which they are allergic for the duration of the study (for food allergy patients)
3. Current use of any allergen immunotherapy.
4. Individuals whose allergen exposures in their home and/or work environments may be expected to change significantly during the trial period
5. Inadequate clinical laboratory parameters at Screening
6. Receipt of or inability to discontinue any excluded therapies
7. Individuals who will decline blood products
8. Active infection
9. Serious mental illness, drug or alcohol abuse, dementia, or other condition that impair ability to sign ICF
10. Individuals who are hypersensitive to intravenous immunoglobulin (IVIg)
11. History of primary immunodeficiency
12. History of CNS disease
13. History of poorly controlled diabetes, chronic kidney disease, chronic pulmonary disease, uncontrolled cardiovascular disease, history of malignancy within 5 years
14. History of severe allergic or anaphylactic reactions to mAb therapy (or recombination antibody-related fusion proteins) or any constituents of study drug
15. Major surgery requiring the use of general anesthesia within 12 weeks prior to Screening or planned or expected major surgery during the study period
16. Blood donation or significant blood loss within 30 days prior to screening
17. Individuals considered to be part of a vulnerable population (eg, incarceration)
18. Individuals that in the opinion of the Investigator, are not suitable for participation in the trial
19. Inability to comply with protocol-mandated requirements
20. A history of severe allergic or anaphylactic reactions related to the underlying IgE mediated disease