Study of CD388 Subcutaneous Administration in Healthy Japanese Subjects

Study Overview
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Brief Summary
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The purpose of this study is to determine the safety and tolerability profile of CD388 Injection, as compared to saline placebo, when dosed by subcutaneous (SQ) administration as a single dose to healthy Japanese adult subjects.

Detailed Description
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This is a Phase 1, single-center, prospective, randomized, double-blind study of ascending single doses of CD388 Injection administered SQ to healthy Japanese adult subjects. The goals are to assess safety, tolerability, and pharmacokinetics (PK) of CD388.

Official Title
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A Phase 1, Randomized, Double-Blind, Single Ascending Dose Study to Determine the Safety, Tolerability, and Pharmacokinetics of CD388 Subcutaneous Administration in Healthy Japanese Subjects

Conditions
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Healthy

Intervention / Treatment
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* Combination Product: CD388 Injection
* Drug: Saline placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must be of Japanese descent with Japanese parents and grandparents, as determined by subject's verbal report. Willing and able to provide written informed consent. Males and females 18 to 65 years of age, inclusive. A female subject must meet one of the following criteria: If of childbearing potential - agrees to use a highly effective, preferably user-independent method of contraception (failure rate of <1 percent per year when used consistently and correctly) for at least 30 days prior to screening and agrees to remain on a highly effective method until 7 months after last dose of study medication, whichever is longer. Examples of highly-effective methods of contraception include: abstinence from heterosexual intercourse; hormonal contraceptives (birth control pills, injectable/implant/insertable hormonal birth control products, transdermal patch); intrauterine device (with or without hormones); or a double barrier method (e.g., condom and spermicide). If a female of non-childbearing potential - should be surgically sterile (i.e., has undergone complete hysterectomy, bilateral oophorectomy, or tubal ligation/occlusion without reversal surgery) or in a menopausal state (at least 1 year without menses), as confirmed by follicle-stimulating hormone (FSH) levels (≥40 milli-International units [mIU]/milliliter [mL]). A woman of childbearing potential must have a negative highly sensitive serum pregnancy test (β-human chorionic gonadotropin) at screening and a negative urine pregnancy test on Day -1 before the first dose of study drug. A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for a period of at least 7 months after study drug administration. A male subject that engages in sexual activity that has the risk of pregnancy must agree to use a double barrier method (e.g., condom and spermicide) and agree to not donate sperm during the study and for at least 7 months after the last dose of the study medication. Good health and without signs or symptoms of current illness. Normal clinical examination, including: No physical examination findings that an Investigator determines would interfere with interpretation of study results. Screening ECG without clinically significant abnormalities. Creatinine clearance (CrCL) ≥80 mL/minute as calculated using the Cockcroft-Gault equation. Negative urine screen for drugs of abuse and alcohol at screening and Day -1. Body weight ≥50 kilograms (kg) and body mass index (BMI; calculated as weight in kg divided by height in meters [m] squared) between 18.0 and 30.0 kg/m^2, inclusive. Willing to refrain from strenuous physical activity that could cause muscle aches or injury, including contact sports, at any time from screening through 30 days after any dose of study drug. Subject has adequate venous access for blood collection. Exclusion Criteria: History of any hypersensitivity or allergic reaction to zanamivir or other neuraminidase inhibitors (i.e., laninamivir, oseltamivir, peramivir), or to excipients of the CD388 Injection drug formulation; or history of drug-induced exfoliative skin disorders (e.g., Stevens-Johnson syndrome [SJS], erythema multiforme, or toxic epidermal necrolysis [TEN]). History of any of the following: Allergies, anaphylaxis, skin rashes (foods such as milk, eggs, medications, vaccines, polyethylene glycol [PEG], etc.). Chronic immune-mediated disease, positive first-degree family history of autoimmune diseases. Atopic dermatitis or psoriasis. Bleeding disorder. Psychiatric condition, seizures, hallucinations, anxiety, depression, or treatment for mental conditions. Migraines. Syncope, or vasovagal syndrome with injections or blood draws. Cardiac arrhythmia considered clinically significant by the Investigator. Subjects with one or more of the following laboratory abnormalities at screening as defined by the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events v2.1 (DAIDS 2017): Serum creatinine, Grade ≥1 (≥1.1 × upper limit of normal [ULN]). Pancreatic amylase or lipase, Grade ≥2 (≥1.5 × ULN). Aspartate aminotransferase (AST) or alanine aminotransferase (ALT), Grade ≥1 (≥1.25 × ULN). Total bilirubin, Grade ≥1 (≥1.1 × ULN). Any other toxicity Grade ≥2, except for Grade 2 elevations of triglycerides, low density lipoprotein cholesterol, and/or total cholesterol. Any other laboratory abnormality considered to be clinically significant by the Investigator. Note: Retesting of abnormal laboratory values that may lead to exclusion will be allowed once without prior asking approval from the Sponsor. Retesting will take place during a scheduled or unscheduled visit during screening. Subjects with a normal value at retest may be included. Alcohol or drug addiction in the past 2 years. Experiencing symptoms of acute illness or chronic disease within 14 days prior to clinical research unit (CRU) check-in. At screening, a positive result for hepatitis B virus surface antigen, hepatitis C virus antibody, or human immunodeficiency virus (HIV) antibody. A positive result at CRU check-in for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by polymerase chain reaction (PCR). Unwilling to comply with local health policy effective at the time regarding coronavirus disease 2019 (COVID-19). Full COVID-19 vaccination prior to participation is strongly recommended. Women who are pregnant or nursing. Received any over-the-counter (OTC) medications or nutritional supplements within 7 days, or any prescription medications within 14 days or <5 half-lives prior to dosing, whichever is longest (except for hormonal contraceptives, acetaminophen, or ibuprofen). Current nicotine user or has quit habitual nicotine use in the 30 days prior to screening. Received any vaccines or immunoglobulins within 28 days prior to dosing (90 days in case of intravenous immunoglobulin [IVIg] or biologics, or 14 days for COVID-19 vaccine). Donated blood (within 56 days of screening) or plasma (within 7 days of screening) or experienced significant blood loss or significant blood draw (blood donation or blood loss ≥500 mL) when participating in non-interventional clinical trials within 30 days prior to dosing. Received a blood transfusion within 28 days prior to dosing. Received any biologics within 90 days prior to dosing; or previous participation in another study (including investigational device studies) within 30 days of dosing or 5 half-lives of the study drug, whichever is longer, prior to screening (prior participation at any time in non-invasive methodology trials in which no drugs were given is acceptable). Previous treatment with CD388. Preplanned surgery at any time during the study. The Principal Investigator (PI) considers that the volunteer should not participate in the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Prevention
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>9 subjects randomized in a 7:2 ratio to receive either 50 mg CD388 SQ injection or matching placebo injection | Combination Product: CD388 Injection<br>* CD388 liquid for injection<br>Drug: Saline placebo<br>* Sterile normal saline for injection<br>|
| Experimental: Cohort 2<br>9 subjects randomized in a 7:2 ratio to receive either 150 mg CD388 SQ injection or matching placebo injection | Combination Product: CD388 Injection<br>* CD388 liquid for injection<br>Drug: Saline placebo<br>* Sterile normal saline for injection<br>|
| Experimental: Cohort 3<br>9 subjects randomized in a 7:2 ratio to receive either 450 mg CD388 SQ injection or matching placebo injection | Combination Product: CD388 Injection<br>* CD388 liquid for injection<br>Drug: Saline placebo<br>* Sterile normal saline for injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and Severity of Treatment-Emergent Adverse Events (TEAEs) after a Single Dose of CD388 | Number of subjects with incidences of TEAEs, including but not limited to adverse events (AEs) and serious adverse events (SAEs) (including systemic reactogenicity/injection site reactions and hypersensitivity reactions), and AEs leading to study drug discontinuation and/or study withdrawal, based on vital signs, electrocardiogram (ECG), and clinical laboratory test (including hematology, coagulation, serum chemistry, and urinalysis) abnormalities following a single dose of CD388. | From Day 1 through the final study visit (Day 120 for Cohort 1; Day 165 for Cohorts 2 and 3) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Plasma Concentration (Cmax) Following CD388 Injection Administration | Evaluation of the maximum plasma concentration (Cmax) following a single dose of CD388. | At inpatient visits on Days 1, 2, 3, 4, 5, 6, 7, 9, 11, and 14; and at outpatient visits on Day 30 (±3 days), Day 45 (±3 days), Day 60 (±5 days), Day 90 (±7 days), and either Day 120 (±14 days) (Cohort 1 only) or Day 165 (±14 days) (Cohorts 2 and 3 only) | 
| Time to Maximum Plasma Concentration (Tmax) Following CD388 Injection Administration | Evaluation of the time to maximum plasma concentration (Tmax) following a single dose of CD388. | At inpatient visits on Days 1, 2, 3, 4, 5, 6, 7, 9, 11, and 14; and at outpatient visits on Day 30 (±3 days), Day 45 (±3 days), Day 60 (±5 days), Day 90 (±7 days), and either Day 120 (±14 days) (Cohort 1 only) or Day 165 (±14 days) (Cohorts 2 and 3 only) | 
| Terminal Elimination Half-life (t½) Following CD388 Injection Administration | Evaluation of the terminal elimination half-life (t½) following a single dose of CD388. | At inpatient visits on Days 1, 2, 3, 4, 5, 6, 7, 9, 11, and 14; and at outpatient visits on Day 30 (±3 days), Day 45 (±3 days), Day 60 (±5 days), Day 90 (±7 days), and either Day 120 (±14 days) (Cohort 1 only) or Day 165 (±14 days) (Cohorts 2 and 3 only) | 
| Apparent Clearance (CL/F) Following CD388 Injection Administration | Evaluation of the apparent clearance (CL/F) following a single dose of CD388. | At inpatient visits on Days 1, 2, 3, 4, 5, 6, 7, 9, 11, and 14; and at outpatient visits on Day 30 (±3 days), Day 45 (±3 days), Day 60 (±5 days), Day 90 (±7 days), and either Day 120 (±14 days) (Cohort 1 only) or Day 165 (±14 days) (Cohorts 2 and 3 only) | 
| Apparent Volume of Distribution (VZ/F) Following CD388 Injection Administration | Evaluation of the apparent volume of distribution (VZ/F) following a single dose of CD388. | At inpatient visits on Days 1, 2, 3, 4, 5, 6, 7, 9, 11, and 14; and at outpatient visits on Day 30 (±3 days), Day 45 (±3 days), Day 60 (±5 days), Day 90 (±7 days), and either Day 120 (±14 days) (Cohort 1 only) or Day 165 (±14 days) (Cohorts 2 and 3 only) | 
| Area Under the Plasma Concentration-Time Curve from Time 0 to Time of Last Quantifiable Sample (AUC[0-t]) Following CD388 Injection Administration | Evaluation of the area under the plasma concentration-time curve from time 0 to time of last quantifiable sample (AUC0-t) following a single dose of CD388. | At inpatient visits on Days 1, 2, 3, 4, 5, 6, 7, 9, 11, and 14; and at outpatient visits on Day 30 (±3 days), Day 45 (±3 days), Day 60 (±5 days), Day 90 (±7 days), and either Day 120 (±14 days) (Cohort 1 only) or Day 165 (±14 days) (Cohorts 2 and 3 only) | 
| Area Under the Plasma Concentration-Time Curve from Time 0 Extrapolated to Infinity (AUC[0-∞]) Following CD388 Injection Administration | Evaluation of the area under the plasma concentration-time curve from time 0 extrapolated to infinity (AUC0-∞) following a single dose of CD388. | At inpatient visits on Days 1, 2, 3, 4, 5, 6, 7, 9, 11, and 14; and at outpatient visits on Day 30 (±3 days), Day 45 (±3 days), Day 60 (±5 days), Day 90 (±7 days), and either Day 120 (±14 days) (Cohort 1 only) or Day 165 (±14 days) (Cohorts 2 and 3 only) |