Study of CD388 for the Prevention of Influenza in Subjects Not at Risk for Influenza Complications

A Phase 2b Randomized, Double-blind, Placebo-controlled, Multicenter Dose Ranging Study to Evaluate Efficacy and Safety of CD388, a Novel Long-acting Antiviral Conjugate, for the Prevention of Influenza in Subjects Not at Risk for Influenza Complications

The purpose of this study is to evaluate the effectiveness of CD388 in preventing symptomatic laboratory-confirmed influenza infections, as compared to placebo, and to select a dose of CD388 that is effective in preventing the same, when administered as a single dose via 3 subcutaneous (SQ) injections to adult participants in stable health, and to evaluate the safety and tolerability of CD388, as compared to placebo.

This is a Phase 2b, randomized, double-blind, placebo-controlled, parallel-group, multicenter dose selection study to evaluate the efficacy, safety, and tolerability of 3 dose levels of CD388 administered as a single dose via 3 SQ injections in adult participants who are not at risk of developing complications from influenza.

Inclusion Criteria:

1. Willing and able to provide written informed consent and comply with scheduled visits, laboratory tests, and other study procedures.

2. Males and females 18 to less than 64 years of age.

3. In the Investigator's clinical judgment, is in stable health at the time of screening and randomization. Participants may not have underlying hematologic, oncologic, renal, autoimmune, and/or cardiopulmonary illnesses or be considered at risk of developing complications from influenza infection per the CDC guidelines (chronic obstructive pulmonary disease [COPD], asthma, immune compromised current cancer [except non-melanomatous skin cancer], or diabetes). Subjects will be included on the basis of medical history and vital signs taken between signing of the informed consent and randomization.

4. Body mass index (BMI; calculated as weight in kilograms [kg] divided by height in meters [m] squared) of 18.0 kg/m^2 to 35.0 kg/m^2 (inclusive).

5. Women of childbearing potential (WOCBP) must:

   1. Have a negative pregnancy test (beta-human chorionic gonadotropin [β-hCG]) at screening, AND
   2. Be practicing a highly effective, preferably user-independent method of contraception (failure rate of less than 1 percent per year when used consistently and correctly) from ≥2 weeks prior to randomization and agrees to remain on a highly effective method from Day 1 until 32 weeks after study drug administration, the end of relevant systemic exposure. The Investigator should evaluate the potential for contraceptive method failure (e.g., noncompliance, recently initiated) in relationship to the day of administration of study drug.

   A woman is considered of childbearing potential (i.e., fertile) following menarche and until becoming postmenopausal, unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient.

6. Female participants must agree not to donate or freeze eggs (ova, oocytes) for future use for the purposes of assisted reproduction from Day 1 until 32 weeks after study drug administration.

7. Male participants must wear a condom when engaging in any activity that allows for passage of ejaculate to another person from Day 1 until 32 weeks after study drug administration. Male participants should also be advised of the benefit for a female partner to additionally use a highly effective method of contraception, as condoms could break or leak.

   Note: Contraceptive (birth control) use by participants should be consistent with local regulations regarding the acceptable methods of contraception for those participating in clinical studies.

8. Male participants must agree not to donate sperm from Day 1 until 32 weeks after study drug administration.

9. Participant agrees not to donate blood from Day 1 until 32 weeks after study drug administration.

10. Must be able to read, understand, and complete questionnaires in the electronic diary (eDiary), work with smartphones/tablets/computers, and be willing and able to adhere to the prohibitions and restrictions specified in this protocol. If an appropriate language version is not available for the eDiary assessments, the participant should not be enrolled.

11. Must be willing to provide verifiable identification, has means to be contacted, and is able to contact the Investigator/study site and communicate reliably during participation in the study.

Exclusion Criteria:

1. Known or suspected allergy or history of anaphylaxis or other serious adverse reactions to zanamivir (following administration of inhaled or intravenous formulations), monoclonal antibodies (including crystallizable fragment [Fc] domains), or any of the components of CD388 or placebo.
2. Have been diagnosed with influenza (i.e., with medical history [including verbal] of influenza) within the past 6 months prior to randomization.
3. Has received the current seasonal influenza vaccine prior to screening or is planning to receive the seasonal vaccine during trial participation.
4. Has an acute illness (including acute respiratory illnesses) or body temperature ≥38.0ºC (≥100.4 degrees Fahrenheit [ºF]) within 7 days prior to study drug administration (Note: Enrollment at a later date, subsequent to resolution [within the screening period] is permitted).
5. Has had close contact (including household contacts) with someone with laboratory-confirmed influenza or with someone who has been treated with antiviral therapies for influenza within the past 7 days prior to randomization.
6. Has had close contact (including household contacts) with someone with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or coronavirus disease 2019 (COVID-19) as defined by the US CDC or has had a positive SARS-CoV-2 test within 10 days prior to screening. Please note SARS-CoV-2 testing is NOT required during screening.
7. Has a serious and/or clinically unstable condition such as psychiatric condition, including recent (within the past year) or active suicidal ideation/behavior, Alzheimer's disease, or any other condition for which, in the opinion of the Investigator, participation would not be in the participant's best interest or that could prevent, confound, or limit the protocol-specified assessments.
8. Any history of alcohol or drug abuse within the past 2 years or a positive urine drug screen for drugs of abuse (other than tetrahydrocannabinol [THC]) at screening or Day 1. Note: urine drug screen that is positive for a medication prescribed for treatment of ongoing condition is not exclusionary.
9. Had major surgery (e.g., major cardiopulmonary or abdominal operations) per Investigator judgment within 4 weeks prior to randomization, or will not have fully recovered from surgery, or has major surgery planned during the time the participant is expected to participate in the study.
10. Screening ECG findings of prolonged QT interval corrected for heart rate using Fridericias formula (QTcF) (greater than 450 milliseconds [msec] in males or greater than 470 msec in females), prolonged PR interval (greater than 220 msec), second- or third-degree heart block, or other clinically significant dysrhythmias.
11. At the time of screening, any finding that may significantly increase the risk of participation in the study, affect the ability to participate in the study, or impair interpretation of the study data.
12. Current or planned participation in another clinical study where study intervention is being administered while participating in the current study. Note: Concurrent enrollment is allowed during the follow-up phase of the other clinical study or in case the study intervention in the other clinical study is a marketed product already approved for another indication - exception being if the other study requires study interventions that could affect the safety assessments of the present study (e.g., clinical laboratory tests).
13. [Exclusion criterion #13 removed during Amendment 1.1-US; placeholder remains to retain numbering of the remaining original exclusion criteria.]
14. Prior receipt within the past 30 days or 5 half-lives (whichever is longer) or anticipated receipt of any drug, vaccine, or other biologic agent (e.g., monoclonal antibodies) administered for the prevention or treatment of influenza.
15. Prior receipt of any experimental drug, vaccine, or biologic agent within the past 90 days or 5 half-lives (whichever is longer).
16. Contraindication to SQ injections and blood draws (e.g., bleeding disorders).
17. Has donated ≥450 mL of blood product (1 unit) for any reason within 30 days of screening or plans to donate blood product during the study.
18. Currently pregnant or breastfeeding, intends to become pregnant or breastfeed, or has a positive pregnancy test during the screening period.
19. Has direct involvement in the proposed study or other studies under the direction of the Investigator, sub-investigators, or study site; is a family member of an individual with such direct involvement; or is an employee of the Sponsor.
20. In the opinion of the Investigator, is unlikely to adhere to the requirements of the study.