Clinical trial NCT06609460: Study of CD388 for the Prevention of Influenza in Subjects Not at Risk for Influenza Complications
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Influenza
Lead sponsor: Cidara Therapeutics Inc.
Sponsor class: INDUSTRY
First posted: 2024-09-24
Enrollment: 5000
Sex: ALL
Minimum age (years): 18
Maximum age (years): 63
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants Experiencing Protocol-defined Influenza-like Illness (ILI) Occurring ≥7 Days after and up to 24 Weeks after Administration of Study Drug
timeFrame: From Day 8 up to 24 weeks after study drug dosing
measure: Incidence and Severity of Treatment-Emergent Adverse Events (TEAEs) after Administration of Study Drug
timeFrame: From Day 1 through Day 197/End of Study (EOS) after study drug dosing
Secondary outcomes:
measure: Percentage of Participants Experiencing Protocol-defined ILI Occurring ≥7 Days after and up to 28 Weeks after Administration of Study Drug
timeFrame: From Day 8 up to 28 weeks after study drug dosing
measure: Percentage of Participants Experiencing Protocol-defined ILI (as in Primary Endpoint 1) Except with a Lower Threshold for New Onset of Fever
timeFrame: From Day 8 up to 24 weeks after study drug dosing
measure: Percentage of Participants Experiencing Protocol-defined ILI (as in Primary Endpoint 1) Except the Influenza Infection is Based on the Midturbinate (MT) Swab Result
timeFrame: From Day 8 up to 24 weeks after study drug dosing
measure: Percentage of Participants Experiencing an Influenza Infection AND New Onset of Fever AND New Onset of ≥2 Respiratory Symptoms after Administration of Study Drug
timeFrame: From Day 8 up to 24 weeks after study drug dosing
measure: Percentage of Participants Experiencing an Influenza Infection AND New Onset of ≥2 Respiratory Symptoms after Administration of Study Drug
timeFrame: From Day 8 up to 24 weeks after study drug dosing
measure: Percentage of Participants Experiencing an Influenza Infection AND New Onset of ≥1 Respiratory Symptom AND New Onset of ≥1 Systemic Symptom after Administration of Study Drug
timeFrame: From Day 8 up to 24 weeks after study drug dosing
measure: Percentage of Participants Experiencing an Influenza Infection, AND New Onset of ≥2 Respiratory Symptoms, OR ≥1 Respiratory Symptom AND New Onset of ≥1 Systemic Symptom, after Administration of Study Drug
timeFrame: From Day 8 up to 24 weeks after study drug dosing
measure: Percentage of Participants Experiencing an Influenza Infection AND New Onset of Fever, AND New Onset of ≥2 Respiratory Symptoms, OR New Onset of ≥1 Respiratory Symptom Plus New Onset of ≥1 Systemic Symptom, after Administration of Study Drug
timeFrame: From Day 8 up to 24 weeks after study drug dosing
measure: Severity (as Composite Symptom Score) of Participant Reported Influenza-like Symptoms as Based on the Self-reported Responses to the Respiratory Infection Intensity and Impact Questionnaire (RiiQ™) Symptom Scale
timeFrame: On Day 1 (pre-dose baseline); and then once daily from the time the participant triggers an ARI Alert in the eDiary until the ARI episode is resolved for a maximum of 29 days per ARI episode, up to 28 weeks after study drug dosing
measure: Severity (as Area Under the Curve [AUC]) of Participant Reported Influenza-like Symptoms as Based on the Self-reported Responses to the RiiQ™ Symptom Scale
timeFrame: On Day 1 (pre-dose baseline); and then once daily from the time the participant triggers an ARI Alert in the eDiary until the ARI episode is resolved for a maximum of 29 days per ARI episode, up to 28 weeks after study drug dosing
measure: Duration (as Time to Symptom Resolution) of Participant Reported Influenza-like Symptoms as Based on the Self-reported Responses to the RiiQ™ Symptom Scale
timeFrame: On Day 1 (pre-dose baseline); and then once daily from the time the participant triggers an ARI Alert in the eDiary until the ARI episode is resolved for a maximum of 29 days per ARI episode, up to 28 weeks after study drug dosing
measure: Trough Plasma Concentration at 24 Weeks (C[trough24w]) Following Administration of CD388
timeFrame: Based on sampling done at onsite visits on Day 85 (±3 days) and Day 197/EOS (±7 days)
measure: Maximum Plasma Concentration (C[max]) Following Administration of CD388
timeFrame: At onsite visits done on Day 8, Day 29, and Day 85 (each ±3 days) and on Day 197/EOS (±7 days)
measure: Area Under the Plasma Concentration-Time Curve (AUC) Following Administration of CD388
timeFrame: At onsite visits done on Day 8, Day 29, and Day 85 (each ±3 days) and on Day 197/EOS (±7 days)
Other outcomes:
Locations:
city: Anniston
country: United States
facility: Pinnacle Research Group, LLC
state: Alabama
city: Cullman
country: United States
facility: Cullman Clinical Trials
state: Alabama
city: Tempe
country: United States
facility: Fiel Family and Sports Medicine/CCT Research
state: Arizona
city: Tucson
country: United States
facility: Del Sol Research Management, LLC
state: Arizona
city: Little Rock
country: United States
facility: Baptist Health Center for Clinical Research
state: Arkansas
city: Huntington Park
country: United States
facility: Velocity Clinical Research - Huntington Park
state: California
city: La Mesa
country: United States
facility: Velocity Clinical Research - San Diego
state: California
city: Montclair
country: United States
facility: Catalina Research Institute, LLC
state: California
city: Oceanside
country: United States
facility: Profound Research LLC
state: California
city: San Diego
country: United States
facility: Acclaim Clinical Research
state: California
city: Colorado Springs
country: United States
facility: Lynn Institute of the Rockies
state: Colorado
city: Lakewood
country: United States
facility: Critical Care, Pulmonary & Sleep Associates, PLLP/CCT Research
state: Colorado
city: Fort Myers
country: United States
facility: Alliance for Multispecialty Research, LLC
state: Florida
city: Inverness
country: United States
facility: Nature Coast Clinical Research
state: Florida
city: Jupiter
country: United States
facility: Health Awareness, LLC
state: Florida
city: Miami Lakes
country: United States
facility: Floridian Clinical Research
state: Florida
city: Miami
country: United States
facility: South Florida Research Center, Inc.
state: Florida
city: Miami
country: United States
facility: Clinical Site Partners, LLC dba Flourish Research
state: Florida
city: North Miami
country: United States
facility: Healthcare Clinical Data, Inc.
state: Florida
city: Atlanta
country: United States
facility: DelRicht Research
state: Georgia
city: Meridian
country: United States
facility: Velocity Clinical Research - Boise
state: Idaho
city: Peoria
country: United States
facility: Optimal Research, LLC
state: Illinois
city: Valparaiso
country: United States
facility: Velocity Clinical Research - Valparaiso
state: Indiana
city: Sioux City
country: United States
facility: Velocity Clinical Research - Sioux City
state: Iowa
city: Lenexa
country: United States
facility: Johnson County Clin-Trials
state: Kansas
city: Louisville
country: United States
facility: DelRicht Research
state: Kentucky
city: Monroe
country: United States
facility: IMA Clinical Research
state: Louisiana
city: New Orleans
country: United States
facility: DelRicht Research
state: Louisiana
city: Prairieville
country: United States
facility: DelRicht Research
state: Louisiana
city: Clarkston
country: United States
facility: Profound Research LLC
state: Michigan
city: Farmington Hills
country: United States
facility: Profound Research LLC
state: Michigan
city: Rochester Hills
country: United States
facility: Profound Research LLC
state: Michigan
city: Gulfport
country: United States
facility: DelRicht Research
state: Mississippi
city: Saint Louis
country: United States
facility: Sundance Clinical Research, LLC
state: Missouri
city: Springfield
country: United States
facility: DelRicht Research
state: Missouri
city: Norfolk
country: United States
facility: Velocity Clinical Research - Norfolk
state: Nebraska
city: Omaha
country: United States
facility: Velocity Clinical Research - Omaha
state: Nebraska
city: Albuquerque
country: United States
facility: Velocity Clinical Research - Albuquerque
state: New Mexico
city: New York
country: United States
facility: IMA Clinical Research
state: New York
city: Charlotte
country: United States
facility: DelRicht Research
state: North Carolina
city: Beachwood
country: United States
facility: Velocity Clinical Research - Cleveland
state: Ohio
city: Cincinnati
country: United States
facility: Velocity Clinical Research - Springdale
state: Ohio
city: Tulsa
country: United States
facility: DelRicht Research
state: Oklahoma
city: Medford
country: United States
facility: Velocity Clinical Research - Medford
state: Oregon
city: Anderson
country: United States
facility: Velocity Clinical Research - Anderson
state: South Carolina
city: Charleston
country: United States
facility: DelRicht Research
state: South Carolina
city: Spartanburg
country: United States
facility: Spartanburg Medical Research
state: South Carolina
city: Hendersonville
country: United States
facility: DelRicht Research
state: Tennessee
city: Dallas
country: United States
facility: Zenos Clinical Research
state: Texas
city: Dallas
country: United States
facility: Lonestar Clinical Research, LLC
state: Texas
city: Prosper
country: United States
facility: DelRicht Research
state: Texas
city: San Antonio
country: United States
facility: Clinical Trials of Texas, LLC dba Flourish Research
state: Texas
city: Stephenville
country: United States
facility: Stephenville Medical & Surgical Clinic
state: Texas
city: Layton
country: United States
facility: Alliance for Multispecialty Research, LLC
state: Utah
city: West Jordan
country: United States
facility: Velocity Clinical Research - Salt Lake City
state: Utah
city: Richmond
country: United States
facility: Clinical Research Partners, LLC
state: Virginia
city: London
country: United Kingdom
facility: hVIVO
Study officials:
affiliation: Cidara Therapeutics Inc.
name: Nicole Davarpanah, MD, JD
role: STUDY_DIRECTOR
References: