Clinical Study of ALT-BB4 to Determine Tolerance, Safety and Pharmacokinetics in Healthy Volunteer

Study Overview
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Brief Summary
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A Phase I Study to Evaluate the Tolerance, Safety and Pharmacokinetics of ALT-BB4 in Healthy Volunteers

Official Title
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A Phase I Study to Evaluate the Tolerance, Safety and Pharmacokinetics of ALT-BB4 in Healthy Volunteer

Conditions
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Health, Subjective

Intervention / Treatment
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* Drug: ALT-BB4
* Drug: 0.9%NaCl


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Common Healthy volunteers aged ≥19 years at the time of Screening (Visit 1) Female subjects or male subjects' female partner must be menopausal or should have received a sterilization procedure or have agreed to use contraceptive methods during the study period, as defined below: Post-menopausal female subjects or male subjects' female partners (non-drug induced amenorrhea for at least 12 months or confirmed diagnosis with menopause) Female subjects or male subjects' female partners who have received a sterilization procedure (removal of ovary and/or uterus) Subjects who have agreed to practice total abstinence during the study period [For female subjects, periodic abstinence (e.g., ovulation, symptothermal, or post-ovulation methods) and withdrawal are not acceptable methods of contraception.] When female subjects or male subjects' female partners are women of childbearing potential (WOCBP) who have not received a sterilization procedure, they must agree to use of following contraceptive methods: Hormones (implantable, patch, and oral) Intrauterine device (IUD) Double barrier methods (concomitant use of two of following contraceptive methods: male condom, female condom, cervical cap, diaphragm, sponge, spermicide) (However, concomitant use of male condom and female condom is excluded from double barrier methods.) WOCBP or females who have the last menstrual period within 12 months must have a negative serum or urine pregnancy test at Screening (Visit 1). Subjects who have voluntarily decided to take part in the study and able to comply with the study protocol Subjects who have no tattoo, acne, dermatitis, pigmentation or lesion on the administration site and who have no damage in the skin, so that they can receive the IP and allergy test Subjects determined eligible for the study through Screening tests (vital signs, physical examination, medical history and surgery history, ECG, and laboratory tests) Part II-A Subjects with BMI no less than 18.5 kg/m2, no greater than 24.9 kg/m2 Exclusion Criteria: Common Subjects who have received or treated with following medications within the specified timeframe prior to Screening (Visit 1) or who are expected to receive them during the study period: Within 1 month: Hyaluronidase, Chemotherapeutic agent, non-steroidal anti-inflammatory drugs (NSAIDs; e.g.: Aspirin, Aceclofenac, etc.), penicillins antibiotics (e.g.: Amoxicillin, Ampicillin, etc.), cephalosporins antibiotics (e.g.: Cefaclor, Cefadroxil, Cefixime, etc.), sulfonamides antibiotics (e.g.: Sulfadiazine, Sulfamethoxazole, etc.), quinolones antibiotics (e.g.: Ciprofloxacin, Levofloxacin, etc.), Glucocorticosteroid, Immunosuppressive agent Within 14 days: Antihistamine (e.g.: Chlorpheniramine, Hydroxyzine, Ketotifen, etc.) Subjects who have prior history of clinically significant liver, kidney, nervous system, immune system, respiratory system, endocrine system, hematology/neoplasm, cardiovascular system, mental (mood disorder, obsessive-compulsive disorder), gastrointestinal disorders or surgical history Subjects with acute fever > 37.5℃ within 7 days from the expected IP administration or showing symptoms suspecting acute diseases within 14 days from the expected IP administration Subjects who do not have normal blood pressure* *Range of normal blood pressure is defined as systolic and diastolic blood <120/80 mmHg in accordance with 2018 Korean Society of Hypertension Guidelines for the Management of Hypertension24) (however, Pre-hypertension (≥ 130/80) is excluded that may occur in normotension). Subjects who persistently drink more than the weekly recommended alcohol units* 14 g of alcohol content per unit is applied, which corresponds to 1 can (small bottle) of beer (5%), 350 mL of draft beer (5%), 1 cup (300 mL) of makgeoli, 1 glass (150 mL) of wine (12%), 1/4 bottle (90 mL) of soju (20%), and 1 shot (45 mL) of liquor (40%). Moderate amount of alcohol by age and gender is provided below:23) Age Recommended unit per week Adults (≥ 19 and < 65 years) Male: 8 units/week Female: 4 units/week Elderly (≥ 65 years) Male: 4 units/week Female: 2 units/week Subjects of usual smoker (exceeding 10 cigarettes per day) Subjects who have a past history of autoimmune diseases (e.g.: rheumatoid arthritis, etc.) or active immune diseases that may affect the immune system [e.g.: flu, cancer, Human immunodeficiency virus (HIV), Hepatitis B virus (HBV), Hepatitis C virus (HCV) etc.], diabetes mellitus, heart diseases, asthma, sinusitis, chronic urticaria, dermographism, or any skin conditions that may affect post-IP administration assessments (e.g.: Dermatitis, dermatomycosis and other skin diseases or tattoo) Subjects with known allergic reactions or hypersensitivity to bee sting or other common allergens or known contraindications to hyaluronidase, thimerosal (disinfectants) and EDTA Subjects with hypersensitivity to the IP or its ingredients or a history of anaphylaxis Past history of drug abuse Subjects who have participated in other clinical trials within 6 months prior to the expected IP administration Others determined ineligible for the study participation in the opinion of investigator Part II-A Subjects who have been treated with a drug-metabolizing enzyme inducers and inhibitors*25), 26) within 30 days prior to the IP administration * Example: Phenytoin, Carbamazepine, Barbiturates, Rifampicin, Griseofulvin, Cimetidine, Disulfiram, Erythromycin, Ketoconazole, Fluconazole, Itraconazole, Valproic acid, Isoniazid, Ciprofloxacin, Omeprazole, Clarithromycin, Quinidine, Sulfonamides, etc. Subjects who have significant bleeding or blood loss within 60 days prior to Screening (Visit 1) Subjects who have donated whole blood within 60 days or donated blood by apheresis within 14 days or received transfusion within 14 days prior to Screening (Visit 1) Subjects who have consumed grapefruit juice28) within 7 days prior to Screening (Visit 1)

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part I (Allergy assessment) - ALT-BB4<br> | Drug: ALT-BB4<br>* Recombinant Hyaluronidase<br>|
| Placebo Comparator: Part I (Allergy assessment) - 0.9%NaCl<br> | Drug: 0.9%NaCl<br>* Normal Saline<br>|
| Experimental: Part II-A (PK assessment)<br> | Drug: ALT-BB4<br>* Recombinant Hyaluronidase<br>|
| Experimental: Part II-B (Safety assessment) - ALT-BB4<br> | Drug: ALT-BB4<br>* Recombinant Hyaluronidase<br>|
| Placebo Comparator: Part II-B (Safety assessment) - 0.9% NaCl<br> | Drug: 0.9%NaCl<br>* Normal Saline<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence rate of drug allergy following ID injection of the IP | Subject developing either immediate or delayed allergic reaction are considered to have drug allergy. | 2 days | 
| Safety and tolerability assessment following SC injection of the IP | Incident rate of adverse events, including systemic and administration site-related adverse events. | 4 weeks |