A Phase 3 Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Safety and Efficacy of CD388, a Novel Long-Acting Antiviral Conjugate, for the Prevention of Influenza in Adults and Adolescents at Higher Risk of Developing Influenza Complications
Trial Snapshot
- Phase
- Phase 3
- Status
- Active, not recruiting
- Enrollment
- 10,000
- Locations
- 489
- Primary Endpoint
- Percentage of Participants Experiencing Protocol-defined Influenza-like Illness (ILI) Occurring ≥7 Days after and up to 24 Weeks after Administration of Study Drug
Study Overview
Brief Summary
Approximately one billion cases of seasonal influenza occur annually. Of these, 3 to 5 million illnesses are severe and responsible for up to 650,000 deaths per year (WHO 2025). Yearly administration of an influenza vaccine for the prevention of influenza is currently recommended. However, the real-world vaccine effectiveness varied from 10% to 60% in the general population across the years of 2004 to 2024, with effectiveness in most years below 50% (CDC 2025) and decreasing to as low as 5% in immunocompromised individuals (Hughes 2021).
The goal of this study is to learn whether MK-1406 (CD388) can help prevent the flu in people who are at higher risk of becoming seriously ill from influenza. Researchers want to find out if MK-1406 dosed at a single study visit can provide protection against influenza compared with placebo. The study will include adolescents and adults who may be more vulnerable to complications from influenza because of their age, health conditions, or weakened immune systems. Researchers will also evaluate the safety of MK-1406 and how well participants tolerate the study medicine.
Detailed Description
This is a Phase 3, randomized, double-blind, placebo-controlled, parallel-group, multicenter study to evaluate the efficacy, safety, and tolerability of MK-1406 (CD388) administered as a single dose via 3 subcutaneous (SC) injections in adult and adolescent participants who are at higher risk of developing complications from influenza.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Prevention
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 12 Years to — (Child, Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •The main inclusion criteria include but are not limited to the following:
- •Primary Stratum A (non-immunocompromised participants who have chronic stable medical conditions) and Primary Stratum B (participants who are immunocompromised either due to underlying disease or receipt of immunosuppressive medications)
- •Has negative rapid antigen tests for influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) prior to dosing at Day 1
- •Weight is ≥ 40 kg
- •Primary Stratum A only
- •Has a history of pulmonary disease
- •Has moderate to severe asthma, as defined by the Global Initiative for Asthma (GINA 2025)
- •Has existing cardiac disease
- •Has insulin-dependent diabetes
- •Has moderate renal impairment
- •Is ≥ 65 years of age at the time of randomization but does not meet any of the above criteria for Primary Stratum A, and is otherwise healthy
- •Primary Stratum B only
- •Has a solid tumor diagnosis AND has received chemotherapy and/or immunotherapy within 1 year of screening
- •Has a diagnosis of a hematologic malignancy within 5 years of screening AND has received any chemotherapy or biologic therapy within 1 year of screening
- •Participants who have had a solid organ transplant (SOT) must satisfy all of the following:
- •Has received a kidney, liver, heart, or lung transplant more than 6 months prior to screening
- •Is currently receiving at least two immunosuppressive medications
- •Participants who have had a hematopoietic stem cell transplant (HSCT) must satisfy at least one of the following:
- •Has a history of hematopoietic stem cell transplantation (HSCT) (i.e., autologous, allogeneic, bone marrow, peripheral blood stem cell, tandem [peripheral blood and marrow]) within 1 year of screening
- •Has a history of non-autologous HSCT with graft-versus-host disease (GvHD) requiring active treatment with immunosuppressants (e.g., systemic corticosteroids ≥1 mg/kg at screening), regardless of the duration of time since HSCT
- •Is receiving immunosuppressive medicines
- •Has received chimeric antigen receptor-modified T-cell therapy
- •Has received B-cell depleting therapies (e.g., rituximab, ocrelizumab, ofatumumab, alemtuzumab) within the 12 months prior to screening
- •Has a diagnosis of any primary immunodeficiency except immunoglobulin A (IgA) deficiency
- •Has advanced or untreated human immunodeficiency virus (HIV) infection
Exclusion Criteria
- •The main exclusion criteria include but are not limited to the following:
- •Known or suspected allergy or history of anaphylaxis or other serious adverse reactions to zanamivir (following administration of inhaled or intravenous formulations), monoclonal antibody (mAbs (including Fc domains)), or any of the components of CD388 or placebo
- •Has an acute (time-limited) or febrile (temperature ≥ 38.0°C [≥ 100.4°F]) illness within 7 days prior to planned dosing on Day 1
- •Has severe chronic kidney disease (CKD) or is receiving hemodialysis
- •Receipt within the past 30 days or 5 half-lives (whichever is longer) or anticipated receipt of any drug or other biologic agent (e.g., mAbs) administered for the prevention or treatment of influenza
- •Has a clinically significant bleeding disorder (e.g., factor deficiency, coagulopathy, or platelet disorder) or medical history of significant bleeding or bruising following intramuscular or subcutaneous (SC) injections or venipuncture
- •Has previously enrolled in this study (CD388.SQ.3.06)
Arms & Interventions
MK-1406
Participants will receive 450 milligrams (mg) dose of MK-1406 (CD388) by subcutaneous (SC) injection.
Intervention: MK-1406 (Combination Product)
Placebo
Participants will receive placebo by SC injection.
Intervention: Placebo (Combination Product)
Outcomes
Primary Outcomes
Percentage of Participants Experiencing Protocol-defined Influenza-like Illness (ILI) Occurring ≥7 Days after and up to 24 Weeks after Administration of Study Drug
Time Frame: From Day 8 up to 24 weeks after study drug dosing
Percentage of participants experiencing protocol-defined ILI occurring after administration of CD388, with influenza infection confirmed by a reverse-transcriptase polymerase chain reaction positive (RT-PCR+) result based on a nasopharyngeal (NP) swab assayed at a central laboratory (first occurrence only), as compared to placebo.
Number of Participants Experiencing Protocol-defined Influenza-like Illness (ILI) Occurring ≥7 Days after and up to 24 Weeks after Administration of Study Drug
Time Frame: Up to approximately 24 weeks post dose
Protocol-defined ILI includes: 1) Influenza infection confirmed by a reverse transcriptase-polymerase chain reaction positive (RT-PCR +) result from nasopharyngeal (NP) swab assayed at a central laboratory AND 2) New onset or worsening of ≥ 2 respiratory symptoms (nasal congestion, sore throat, or cough) OR New onset or worsening of 1 respiratory symptom (nasal congestion, sore throat, or cough) AND new onset of ≥ 1 systemic symptom (headache, feeling feverish or chills, body aches/pains, or fatigue). Number of participants experiencing protocol-defined ILI occurring after administration of MK-1406 (CD388), with influenza infection confirmed by an RT-PCR+ result based on a NP swab assayed at a central laboratory (first occurrence only), as compared to placebo will be assessed.
Percentage of Participants Experiencing Protocol-defined Influenza-like Illness (ILI) Occurring ≥7 Days after and up to 24 Weeks after Administration of Study Drug
Time Frame: From Day 8 up to 24 weeks after study drug dosing
Percentage of participants experiencing protocol-defined ILI occurring after administration of CD388, with influenza infection confirmed by a reverse-transcriptase polymerase chain reaction positive (RT-PCR+) result based on a nasopharyngeal (NP) swab assayed at a central laboratory (first occurrence only), as compared to placebo.
Secondary Outcomes
- Percentage of Stratum B Participants Experiencing Protocol-defined Influenza-like Illness (ILI) Occurring ≥7 Days after and up to 24 Weeks after Administration of Study Drug(From Day 8 up to 24 weeks after study drug dosing)
- All-cause Hospitalization within 30 Days after the Onset of Symptomatic Influenza(From Day 8 up to 24 weeks after study drug dosing)
- All-cause Mortality within 30 Days after the Onset of Symptomatic Influenza(From Day 8 up to 24 weeks after study drug dosing)
- Trough Plasma Concentration at 24 Weeks (C[trough24w]) Following Administration of CD388(Based on sampling done on Day 1 (pre-dose baseline) and at onsite visits on Day 8 (±3 days), Day 29 (±3 days), and Day 197/EOS (±7 days))
- Maximum Plasma Concentration (C[max]) Following Administration of CD388(On Day 1 (pre-dose baseline) and at onsite visits done on Day 8 (±3 days), Day 29 (±3 days), and Day 197/EOS (±7 days))
- Area Under the Plasma Concentration-Time Curve (AUC) Following Administration of CD388(On Day 1 (pre-dose baseline) and at onsite visits done on Day 8 (±3 days), Day 29 (±3 days), and Day 197/EOS (±7 days))
- Detection of Treatment-emergent Anti-Drug Antibodies (ADAs) in Participants Administered CD388(On Day 1 (pre-dose baseline) and at onsite visits done on Day 29 (±3 days) and Day 197/EOS (±7 days))
- Detection of Treatment-boosted Anti-Drug Antibodies (ADAs) in Participants Administered CD388(On Day 1 (pre-dose baseline) and at onsite visits done on Day 29 (±3 days) and Day 197/EOS (±7 days))
- Number of participants with ≥1 Adverse Event (AE)(Up to approximately Day 197)
- Number of Participants Who Discontinued from the Study Due to an AE(Up to approximately Day 197)
- Number of Participants with Injection Site Reactions (ISRs)(Up to approximately Day 8 post dose)
- Number of Stratum B Participants Experiencing Protocol-defined Influenza-like Illness (ILI) Occurring ≥7 Days after and up to 24 Weeks after Administration of Study Drug(Up to approximately 24 weeks post dose)
- Number of Participants with All-cause Hospitalization within 30 Days after the Onset of Symptomatic Laboratory-Confirmed Influenza(Up to 30 days after onset of symptomatic laboratory-confirmed influenza)
- Number of Participants with All-cause Mortality within 30 Days after the Onset of Symptomatic Laboratory-Confirmed Influenza(Up to 30 days after onset of symptomatic laboratory-confirmed influenza)
- Plasma Concentrations Following Administration of MK-1406 (CD388)(Day 1 (pre-dose), Day 29, and Day 197 post dose)
- Number of Participants with Treatment Emergent Anti-Drug Antibodies (ADAs)(Day 1 (pre-dose), Day 29, and Day 197 post dose)
- Number of Participants with Treatment Boosted ADAs(Day 1 (pre-dose), Day 29, and Day 197 post dose)
- Incidence and Severity of Treatment-Emergent Adverse Events (TEAEs) after Administration of Study Drug(From Day 1 through Day 197/End of Study (EOS) after study drug dosing)
- Trough Plasma Concentration at 24 Weeks (C[trough24w]) Following Administration of CD388(Based on sampling done at onsite visits on Day 8 (±3 days), Day 29 (±3 days), and Day 197/EOS (±7 days))
- Maximum Plasma Concentration (C[max]) Following Administration of CD388(At onsite visits done on Day 8 (±3 days), Day 29 (±3 days), and Day 197/EOS (±7 days))
- Area Under the Plasma Concentration-Time Curve (AUC) Following Administration of CD388(At onsite visits done on Day 8 (±3 days), Day 29 (±3 days), and Day 197/EOS (±7 days))
- Detection of Anti-Drug Antibodies (ADAs) in Participants Administered CD388(On Day 1 (pre-dose baseline) and at onsite visits done on Day 29 (±3 days) and Day 197/EOS (±7 days))