Study of CD388 Intramuscular or Subcutaneous Administration in Healthy Subjects

Study Overview
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Brief Summary
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The purpose of this first-in-human study is to determine the safety and tolerability profile of CD388 Injection, as compared to saline placebo, when administered as a single dose to healthy adult subjects by injection either in the muscle or under the skin.

Detailed Description
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A Phase 1, single-center, prospective, randomized, double-blind, single-dose and repeat single-dose, dose-escalation study to determine the safety, tolerability, and pharmacokinetics of CD388 Injection, as compared to saline placebo, when dosed either by intramuscular (IM) or subcutaneous (SQ) administration to healthy adult subjects.

Official Title
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A Phase 1, Randomized, Double-Blind, Single-Dose and Repeat Single-Dose, Dose-Escalation Study to Determine the Safety, Tolerability, and Pharmacokinetics of CD388 Intramuscular or Subcutaneous Administration in Healthy 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: 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 205 days after last dose of study medication. 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) 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 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 until at least 205 days 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 mass index (BMI; weight in kilograms [kg] divided by height in meters [m] squared) between 18.0 and 32.0 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. Subjects with one or more of the following laboratory abnormalities at screening as defined by the 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 check-in to the clinical research unit (CRU). 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 screening or CRU check-in for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by polymerase chain reaction (PCR). Beginning with Protocol Amendment 2, antigen testing may be used if PCR is not available. Unwilling to comply with local health policy effective at the time regarding coronavirus disease 2019 (COVID-19).* 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. 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 when participating in non-interventional clinical trials within 60 days prior to dosing. Received a blood transfusion within 28 days prior to dosing. Received any biologics within 90 days prior to dosing. Previous participation in another study within 30 days 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. The PI considers that the volunteer should not participate in the study. (*) Full COVID-19 vaccination prior to participation is strongly recommended. (**) In the event a subject chooses to receive one of the two 2-dose approved or emergency-use-authorized COVID 19 vaccines (Comirnaty® [Pfizer], Spikevax™ [Moderna]) in the interval between two CRU stays (Cohort 2A/2B or Cohort 3A/3B), flexibility in timing of the second CRU stay should be applied, to allow appropriate receipt of the second vaccine dosage or booster (based on the respective vaccine label) + 14 days, to minimize risk of confounding findings/observations.

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 1A (sentinel)<br>Low dose level: 2 subjects randomized at a ratio of 1:1 to receive a single dose of 50 mg CD388 or placebo, administered by IM injection | Combination Product: CD388 Injection<br>* CD388 liquid for injection<br>Drug: Saline placebo<br>* Sterile normal saline for injection<br>|
| Experimental: Cohort 1A (main)<br>Low dose level: 9 subjects randomized at a ratio of 7:2 to receive a single dose of 50 mg CD388 or placebo, administered by IM injection | Combination Product: CD388 Injection<br>* CD388 liquid for injection<br>Drug: Saline placebo<br>* Sterile normal saline for injection<br>|
| Experimental: Cohort 1B (sentinel)<br>Low dose level: 2 subjects randomized at a ratio of 1:1 to receive a single dose of 50 mg CD388 or placebo, administered by SQ injection | Combination Product: CD388 Injection<br>* CD388 liquid for injection<br>Drug: Saline placebo<br>* Sterile normal saline for injection<br>|
| Experimental: Cohort 1B (main)<br>Low dose level: 9 subjects randomized at a ratio of 7:2 to receive a single dose of 50 mg CD388 or placebo, administered by SQ injection | Combination Product: CD388 Injection<br>* CD388 liquid for injection<br>Drug: Saline placebo<br>* Sterile normal saline for injection<br>|
| Experimental: Cohort 2A (sentinel)<br>Mid dose level: 2 subjects randomized at a ratio of 1:1 to receive a single dose of 150 mg CD388 or placebo, administered by IM injection, followed by another single dose of the same treatment (CD388 or placebo) administered by the same route after washout of 5 effective half-lives after the first dose | Combination Product: CD388 Injection<br>* CD388 liquid for injection<br>Drug: Saline placebo<br>* Sterile normal saline for injection<br>|
| Experimental: Cohort 2A (main)<br>Mid dose level: 9 subjects randomized at a ratio of 7:2 to receive a single dose of 150 mg CD388 or placebo, administered by IM injection, followed by another single dose of the same treatment (CD388 or placebo) administered by the same route after washout of 5 effective half-lives after the first dose | Combination Product: CD388 Injection<br>* CD388 liquid for injection<br>Drug: Saline placebo<br>* Sterile normal saline for injection<br>|
| Experimental: Cohort 2B (sentinel)<br>Mid dose level: 2 subjects randomized at a ratio of 1:1 to receive a single dose of 150 mg CD388 or placebo, administered by SQ injection, followed by another single dose of the same treatment (CD388 or placebo) administered by the same route after washout of 5 effective half-lives after the first dose | Combination Product: CD388 Injection<br>* CD388 liquid for injection<br>Drug: Saline placebo<br>* Sterile normal saline for injection<br>|
| Experimental: Cohort 2B (main)<br>Mid dose level: 9 subjects randomized at a ratio of 7:2 to receive a single dose of 150 mg CD388 or placebo, administered by SQ injection, followed by another single dose of the same treatment (CD388 or placebo) administered by the same route after washout of 5 effective half-lives after the first dose | Combination Product: CD388 Injection<br>* CD388 liquid for injection<br>Drug: Saline placebo<br>* Sterile normal saline for injection<br>|
| Experimental: Cohort 3A (sentinel)<br>High dose level: 2 subjects randomized at a ratio of 1:1 to receive a single dose of 450 mg CD388 or placebo, administered by IM injection, followed by another single dose of the same treatment (CD388 or placebo) administered by the same route after washout of 5 effective half-lives after the first dose | Combination Product: CD388 Injection<br>* CD388 liquid for injection<br>Drug: Saline placebo<br>* Sterile normal saline for injection<br>|
| Experimental: Cohort 3A (main)<br>High dose level: 9 subjects randomized at a ratio of 7:2 to receive a single dose of 450 mg CD388 or placebo, administered by IM injection, followed by another single dose of the same treatment (CD388 or placebo) administered by the same route after washout of 5 effective half-lives after the first dose | Combination Product: CD388 Injection<br>* CD388 liquid for injection<br>Drug: Saline placebo<br>* Sterile normal saline for injection<br>|
| Experimental: Cohort 3B (sentinel)<br>High dose level: 2 subjects randomized at a ratio of 1:1 to receive a single dose of 450 mg CD388 or placebo, administered by SQ injection, followed by another single dose of the same treatment (CD388 or placebo) administered by the same route after washout of 5 effective half-lives after the first dose | Combination Product: CD388 Injection<br>* CD388 liquid for injection<br>Drug: Saline placebo<br>* Sterile normal saline for injection<br>|
| Experimental: Cohort 3B (main)<br>High dose level: 9 subjects randomized at a ratio of 7:2 to receive a single dose of 450 mg CD388 or placebo, administered by SQ injection, followed by another single dose of the same treatment (CD388 or placebo) administered by the same route after washout of 5 effective half-lives after the first dose | Combination Product: CD388 Injection<br>* CD388 liquid for injection<br>Drug: Saline placebo<br>* Sterile normal saline for injection<br>|
| Experimental: Cohort 4B (sentinel)<br>Highest dose level: 2 subjects randomized at a ratio of 1:1 to receive a single dose of 900 mg CD388 or placebo, administered by SQ injection | Combination Product: CD388 Injection<br>* CD388 liquid for injection<br>Drug: Saline placebo<br>* Sterile normal saline for injection<br>|
| Experimental: Cohort 4B (main)<br>Highest dose level: 9 subjects randomized at a ratio of 7:2 to receive a single dose of 900 mg CD388 or placebo, administered by SQ 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) based on vital signs, electrocardiogram (ECG), and clinical laboratory test (hematology, coagulation, serum chemistry, and urinalysis) abnormalities following a single dose of CD388 | Day 1 through Day 120 (±14 days) (Cohorts 1A/1B only), or Day 1 through Day 206 (±10 days) (Cohorts 2A/2B, 3A/3B, and 4B) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak Plasma Concentration (Cmax) Following CD388 Injection Administration | Evaluation of maximum plasma concentration (Cmax) following a single dose of CD388 and following a repeated single dose of CD388. | Days 1 through 7, 9, 11, 14, 21, and 30 (all cohorts) and at outpatient visits: Days 45, 60, 90, and 120 (Cohorts 1A/1B only); Days 45, 84, 126, 168, 251, 290, 332, and 374 (Cohorts 2A/2B and 3A/3B); or Days 45, 84, 126, 168, and 206 (Cohort 4B only) | 
| Time to Maximum Plasma Concentration (Tmax) Following CD388 Injection Administration | Evaluation of time to maximum plasma concentration (Tmax) following a single dose of CD388 and following a repeated single dose of CD388. | Days 1 through 7, 9, 11, 14, 21, and 30 (all cohorts) and at outpatient visits: Days 45, 60, 90, and 120 (Cohorts 1A/1B only); Days 45, 84, 126, 168, 251, 290, 332, and 374 (Cohorts 2A/2B and 3A/3B); or Days 45, 84, 126, 168, and 206 (Cohort 4B only) | 
| Terminal Elimination Half-life (t½) Following CD388 Injection Administration | Evaluation of terminal elimination half-life (t½) following a single dose of CD388 and following a repeated single dose of CD388. | Days 1 through 7, 9, 11, 14, 21, and 30 (all cohorts) and at outpatient visits: Days 45, 60, 90, and 120 (Cohorts 1A/1B only); Days 45, 84, 126, 168, 251, 290, 332, and 374 (Cohorts 2A/2B and 3A/3B); or Days 45, 84, 126, 168, and 206 (Cohort 4B only) | 
| Apparent Clearance (CL/F) Following CD388 Injection Administration | Evaluation of apparent clearance (CL/F) following a single dose of CD388 and following a repeated single dose of CD388. | Days 1 through 7, 9, 11, 14, 21, and 30 (all cohorts) and at outpatient visits: Days 45, 60, 90, and 120 (Cohorts 1A/1B only); Days 45, 84, 126, 168, 251, 290, 332, and 374 (Cohorts 2A/2B and 3A/3B); or Days 45, 84, 126, 168, and 206 (Cohort 4B only) | 
| Apparent Volume of Distribution (VZ/F) Following CD388 Injection Administration | Evaluation of apparent volume of distribution (VZ/F) following a single dose of CD388 and following a repeated single dose of CD388. | Days 1 through 7, 9, 11, 14, 21, and 30 (all cohorts) and at outpatient visits: Days 45, 60, 90, and 120 (Cohorts 1A/1B only); Days 45, 84, 126, 168, 251, 290, 332, and 374 (Cohorts 2A/2B and 3A/3B); or Days 45, 84, 126, 168, and 206 (Cohort 4B 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 area under the plasma concentration-time curve from time 0 to time of last quantifiable sample (AUC[0-t]) following a single dose of CD388 and following a repeated single dose of CD388. | Days 1 through 7, 9, 11, 14, 21, and 30 (all cohorts) and at outpatient visits: Days 45, 60, 90, and 120 (Cohorts 1A/1B only); Days 45, 84, 126, 168, 251, 290, 332, and 374 (Cohorts 2A/2B and 3A/3B); or Days 45, 84, 126, 168, and 206 (Cohort 4B only) | 
| Area Under the Plasma Concentration-Time Curve from Time 0 Extrapolated to Infinity (AUC[0-∞]) Following CD388 Injection Administration | Evaluation of area under the plasma concentration-time curve from time 0 extrapolated to infinity (AUC[0-∞]) following a single dose of CD388 and following a repeated single dose of CD388. | Days 1 through 7, 9, 11, 14, 21, and 30 (all cohorts) and at outpatient visits: Days 45, 60, 90, and 120 (Cohorts 1A/1B only); Days 45, 84, 126, 168, 251, 290, 332, and 374 (Cohorts 2A/2B and 3A/3B); or Days 45, 84, 126, 168, and 206 (Cohort 4B only) | 
| Incidence and Severity of Treatment-Emergent Adverse Events (TEAEs) after a Repeated 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) based on vital signs, ECG, and clinical laboratory test (hematology, coagulation, serum chemistry, and urinalysis) abnormalities following a repeated single dose of CD388 | Day 207 through Day 412 (±10 days) (Cohorts 2A/2B and 3A/3B only) |