A Clinical Study to Evaluate an Experimental Universal Influenza Vaccine, INFLUENZA G1 mHA, in Healthy Adults

Study Overview
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Brief Summary
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The primary purpose of this study is to evaluate safety/ reactogenicity of INFLUENZA G1 mini-hemagglutinin stem-derived protein vaccine antigen (mHA), with or without Al(OH)3 adjuvant, in healthy adults greater than or equal to (>=) 18 to less than or equal to (<=) 45 years of age.

Official Title
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A Randomized, Double-blind, Placebo-controlled, First-in-human Phase 1/2a Study to Evaluate Safety, Reactogenicity and Immunogenicity of a Universal Influenza (Uniflu) Vaccine With INFLUENZA G1 mHA in Healthy Adults

Conditions
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Influenza Prevention

Intervention / Treatment
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* Biological: INFLUENZA G1 mHA
* Biological: Placebo
* Biological: Al(OH)3


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must be healthy as confirmed by medical history, physical examination, vital signs, and clinical laboratory tests performed at screening Contraceptive (birth control) use by female participants should be consistent with local regulations regarding the acceptable methods of contraception for those participating in clinical studies. Before randomization, participants who were born female must be either: a) not of childbearing potential; b) of childbearing potential and practicing a highly effective method of contraception and agreeing to remain on such a method of contraception from signing the informed consent until 3 months after the last dose of study vaccine. Use of hormonal contraception should start at least 28 days before the first administration of study vaccine. Highly effective methods for this study include: hormonal contraception, intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion/ligation procedures, vasectomized partner (the vasectomized partner should be the sole partner for that participant), and sexual abstinence All female participants of childbearing potential must: a) have a negative highly sensitive serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test at screening; b) have a negative urine beta-hCG pregnancy test immediately prior to each study vaccine administration Must be healthy on the basis of clinical laboratory tests performed at screening. If the results of the laboratory screening tests are outside the laboratory normal reference ranges and additionally within the limits of toxicity Grade 2 according to the US FDA toxicity scale the participant may be included only if the investigator judges the abnormalities or deviations from normal to be not clinically significant and appropriate and reasonable for the population under study. This determination must be recorded in the participant's source documents and initialed by the investigator Exclusion Criteria: Contraindication to IM injections and blood draws, example, bleeding disorders Clinically significant acute illness (this does not include minor illnesses such as diarrhea or mild upper respiratory tract infection) or temperature greater than or equal to (>=) 38.0 degree Celsius (100.4 degree Fahrenheit) within 24 hours prior to the planned first dose of study vaccine; randomization at a later date is permitted at the discretion of the investigator and after consultation with the sponsor History of severe allergic reaction (for example, anaphylaxis) or other serious adverse reactions to vaccines or vaccine excipients (specifically the excipients of the study vaccine[s]) Abnormal function of the immune system resulting from: a) clinical conditions (example, autoimmune disease or immunodeficiency) or their treatments expected to have an impact on the immune response elicited by the study vaccine; b) chronic or recurrent use of systemic corticosteroids within 2 months before administration of study vaccine and during the study; c) administration of antineoplastic and immunomodulating agents or radiotherapy expected to have an impact on the immune response elicited by the study vaccine within 6 months before administration of study vaccine and during the study History of acute polyneuropathy (example, Guillain-Barré syndrome) or chronic idiopathic demyelinating polyneuropathy Received treatment with immunoglobulins (including monoclonal antibodies) expected to impact the vaccine-induced immune response in the 2 months or blood products in the 3 months before the planned administration of the first dose of study vaccine or has any plans to receive such treatment during the study. Received an investigational drug or used an invasive investigational medical device within 30 days or received an investigational vaccine within 6 months before the planned administration of the first dose of study vaccine, or received an investigational biological product within 3 months or 5 half-lives, whichever is longer, before the planned study intervention, or is currently enrolled or plans to participate in another investigational study or observational clinical study during the course of this study Pregnant, or breastfeeding, or planning to become pregnant while enrolled in this study or within 3 months after the last dose of study vaccine. Oocyte donation is prohibited while enrolled in this study Received or plans to receive: licensed live attenuated vaccines - within 28 days before or after planned administration of the first or subsequent study vaccination[s]; other licensed (not live) vaccines (not including seasonal influenza vaccines) - within 14 days before or after planned administration of the first or subsequent study vaccination[s]; seasonal influenza vaccines - within 4 months before planned administration of the first study vaccination until the end of the study (that is, any individual who requires a seasonal influenza vaccination for occupational or other reasons will be excluded) Has received a pandemic influenza vaccine (other than Hemagglutinin Type 1 and Neuraminidase Type 1 [H1N1]) in a previous pandemic influenza vaccine study at any time prior to randomization

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: INFLUENZA G1 mHA Dose Level 1<br>Participants will receive single intramuscular (IM) injection of INFLUENZA G1 mHA Dose level 1 on Days 1 and 57 in Cohort 1. | Biological: INFLUENZA G1 mHA<br>* INFLUENZA G1 mHA will be administered intramuscularly.<br>|
| Experimental: INFLUENZA G1 mHA Dose Level 1 along with Al(OH)3<br>Participants will receive single IM injection of INFLUENZA G1 mHA Dose level 1 with Aluminum Hydroxide (Al[OH])3 adjuvant on Days 1 and 57 in Cohort 1. | Biological: INFLUENZA G1 mHA<br>* INFLUENZA G1 mHA will be administered intramuscularly.<br>Biological: Al(OH)3<br>* Al(OH)3 will be administered intramuscularly.<br>|
| Placebo Comparator: Placebo<br>Participants will receive IM injection of placebo on Days 1 and 57 in Cohorts 1 and 2. | Biological: Placebo<br>* Placebo will be administered intramuscularly.<br>|
| Experimental: INFLUENZA G1 mHA Dose Level 2<br>Participants will receive single IM injection of INFLUENZA G1 mHA Dose level 2 on Days 1 and 57 in Cohort 2. | Biological: INFLUENZA G1 mHA<br>* INFLUENZA G1 mHA will be administered intramuscularly.<br>|
| Experimental: INFLUENZA G1 mHA Dose Level 2 along with Al(OH)3<br>Participants will receive single IM injection of INFLUENZA G1 mHA Dose level 2 with Al(OH)3 adjuvant on Days 1 and 57 in Cohort 2. | Biological: INFLUENZA G1 mHA<br>* INFLUENZA G1 mHA will be administered intramuscularly.<br>Biological: Al(OH)3<br>* Al(OH)3 will be administered intramuscularly.<br>|
| Experimental: INFLUENZA G1 mHA Dose Level 2 + Placebo<br>Participants will receive single IM injection of INFLUENZA G1 mHA Dose level 2 on Day 1 and placebo on Day 57 in Cohort 2. | Biological: INFLUENZA G1 mHA<br>* INFLUENZA G1 mHA will be administered intramuscularly.<br>|
| Experimental: INFLUENZA G1 mHA Dose Level 2 along with Al(OH)3 + Placebo<br>Participants will receive single IM injection of INFLUENZA G1 mHA Dose level 2 with Al(OH)3 adjuvant on Day 1 and placebo on Day 57 in Cohort 2. | Biological: INFLUENZA G1 mHA<br>* INFLUENZA G1 mHA will be administered intramuscularly.<br>Biological: Al(OH)3<br>* Al(OH)3 will be administered intramuscularly.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Solicited Local Adverse Events (AEs) at 7 Days Post-vaccination 1 | Number of participants with solicited local AEs at 7 days post-vaccination 1 will be reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Solicited local AEs are pre-defined local (at the injection site) AEs for which participants will be specifically questioned and which will be noted by participants in diary for 7 days post vaccination (day of vaccination and the subsequent 7 days). Solicited local AEs are injection site pain/tenderness, erythema, and swelling at the vaccination site. All solicited AEs at the injection site will be considered related to the study vaccine administration. | 7 Days after vaccination 1 on Day 1 (Day 8) | 
| Number of Participants with Solicited Local AEs at 7 Days Post-vaccination 2 | Number of participants with solicited local AEs at 7 days post-vaccination 2 will be reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Solicited local AEs are pre-defined local (at the injection site) AEs for which participants will be specifically questioned and which will be noted by participants in their diary for 7 days post vaccination (day of vaccination and the subsequent 7 days). Solicited local AEs are injection site pain/tenderness, erythema, and swelling at the vaccination site. All solicited AEs at the injection site will be considered related to the study vaccine administration. | 7 Days after vaccination 2 on Day 57 (Day 64) | 
| Number of Participants with Solicited Local AEs by Severity at 7 Days Post-vaccination 1 | Number of participants with solicited local AEs by severity at 7 days post-vaccination 1 will be reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Solicited local AEs are pre-defined local (at the injection site) AEs for which participants will be specifically questioned and which will be noted by participants in their diary for 7 days post vaccination (day of vaccination and the subsequent 7 days). Solicited local AEs are injection site pain/tenderness, erythema, and swelling at the vaccination site. Severity will be assessed using Food and Drug Administration (FDA) Toxicity grading scale which includes Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe) and Grade 4 (potentially life threatening). | 7 Days after vaccination 1 on Day 1 (Day 8) | 
| Number of Participants with Solicited Local AEs by Severity at 7 Days Post-vaccination 2 | Number of participants with solicited local AEs by severity at 7 days post-vaccination 2. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Solicited local AEs are pre-defined local (at the injection site) AEs for which participants will be specifically questioned and which will be noted by participants in their diary for 7 days post vaccination (day of vaccination and the subsequent 7 days). Solicited local AEs are injection site pain/tenderness, erythema, and swelling at the vaccination site. Severity will be assessed using FDA Toxicity grading scale which includes Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe) and Grade 4 (potentially life threatening). | 7 Days after vaccination 2 on Day 57 (Day 64) | 
| Duration of Solicited Local AEs at 7 Days Post-vaccination 1 | Duration of solicited local AEs on at 7 days post-vaccination 1 will be reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Solicited local AEs are pre-defined local (at the injection site) AEs for which participants will be specifically questioned and which will be noted by participants in their diary for 7 days post vaccination (day of vaccination and the subsequent 7 days). Solicited local AEs are injection site pain/tenderness, erythema, and swelling at the vaccination site. | 7 Days after vaccination 1 on Day 1 (Day 8) | 
| Duration of Solicited Local AEs at 7 Days Post-vaccination 2 | Duration of solicited local AEs at 7 days post-vaccination 2 will be reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Solicited local AEs are pre-defined local (at the injection site) AEs for which participants will be specifically questioned and which will be noted by participants in their diary for 7 days post vaccination (day of vaccination and the subsequent 7 days). Solicited local AEs are injection site pain/tenderness, erythema, and swelling at the vaccination site. | 7 Days after vaccination 2 on Day 57 (Day 64) | 
| Number of Participants with Solicited Systemic AEs at 7 Days Post-vaccination 1 | Number of participants with solicited systemic AEs at 7 days post-vaccination 1 will be reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Participants will be instructed on how to note signs and symptoms in their diary on a daily basis for 7 days post-vaccination (Day of vaccination and the subsequent 7 days) for solicited systemic AEs. Solicited systemic AEs include fatigue, headache, myalgia, nausea, and fever (body temperature greater than or equal to [>=] 38 degree C). | 7 Days after vaccination 1 on Day 1 (Day 8) | 
| Number of Participants with Solicited Systemic AEs at 7 Days Post-vaccination 2 | Number of participants with solicited systemic AEs at 7 days post-vaccination 2 will be reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Participants will be instructed on how to note signs and symptoms in their diary on a daily basis for 7 days post-vaccination (Day of vaccination and the subsequent 7 days) for solicited systemic AEs. Solicited systemic AEs include fatigue, headache, myalgia, nausea, and fever (body temperature >=38 degree C). | 7 Days after vaccination 2 on Day 57 (Day 64) | 
| Number of Participants with Solicited Systemic AEs by Severity at 7 Days Post-vaccination 1 | Number of participants with solicited systemic AEs by severity at 7 days post-vaccination 1 will be reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Participants will be instructed on how to note signs and symptoms in their diary on a daily basis for 7 days post-vaccination (Day of vaccination and the subsequent 7 days) for solicited systemic AEs. Solicited systemic AEs include fatigue, headache, myalgia, nausea, and fever (body temperature >=38 degree C). Severity will be assessed using FDA Toxicity grading scale which includes Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe) and Grade 4 (potentially life threatening). | 7 Days after vaccination 1 on Day 1 (Day 8) | 
| Number of Participants with Solicited Systemic AEs by Severity at 7 Days Post-vaccination 2 | Number of participants with solicited systemic AEs by severity at 7 days post-vaccination 2 will be reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Participants will be instructed on how to note signs and symptoms in their diary on a daily basis for 7 days post-vaccination (Day of vaccination and the subsequent 7 days) for solicited systemic AEs. Solicited systemic AEs include fatigue, headache, myalgia, nausea and fever (body temperature >=38 degree C). Severity will be assessed using FDA Toxicity grading scale which includes Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe) and Grade 4 (potentially life threatening). | 7 Days after vaccination 2 on Day 57 (Day 64) | 
| Duration of Solicited Systemic AEs at 7 Days Post-vaccination 1 | Duration of solicited systemic AEs on at 7 days post-vaccination 1 will be reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Participants will be instructed on how to note signs and symptoms in their diary on a daily basis for 7 days post-vaccination (Day of vaccination and the subsequent 7 days) for solicited systemic AEs. Solicited systemic AEs include fatigue, headache, myalgia, nausea and fever (body temperature >=38 degree C). | 7 Days after vaccination 1 on Day 1 (Day 8) | 
| Duration of Solicited Systemic AEs at 7 Days Post-vaccination 2 | Duration of solicited systemic AEs on at 7 days post-vaccination 2 will be reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Participants will be instructed on how to note signs and symptoms in their diary on a daily basis for 7 days post-vaccination (Day of vaccination and the subsequent 7 days) for solicited systemic AEs. Solicited systemic AEs include fatigue, headache, myalgia, nausea, and fever (body temperature >=38 degree C). | 7 Days after vaccination 2 on Day 57 (Day 64) | 
| Number of Participants with Solicited Systemic AEs Related to Study Vaccine at 7 Days Post-vaccination 1 | Number of participants with solicited systemic AEs related to study vaccine at 7 days post-vaccination 1 will be reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Participants will be instructed on how to note signs and symptoms in their diary on a daily basis for 7 days post-vaccination (Day of vaccination and the subsequent 7 days) for solicited systemic AEs. Solicited systemic AEs include fatigue, headache, myalgia, nausea, and fever (body temperature >=38 degree C). | 7 Days after vaccination 1 on Day 1 (Day 8) | 
| Number of Participants with Solicited Systemic AEs Related to Study Vaccine at 7 Days Post-vaccination 2 | Number of participants with solicited systemic AEs related to study vaccine at 7 days post-vaccination 2 will be reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Participants will be instructed on how to note signs and symptoms in their diary on a daily basis for 7 days post-vaccination (Day of vaccination and the subsequent 7 days) for solicited systemic AEs. Solicited systemic AEs include fatigue, headache, myalgia, nausea, and fever (body temperature >=38 degree C). | 7 Days after vaccination 2 on Day 57 (Day 64) | 
| Number of Participants with Unsolicited AEs at 28 Days Post-vaccination 1 | Number of participants with unsolicited AEs at 28 days post-vaccination 1 will be reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Unsolicited AEs are all AEs for which the participant is not specifically questioned in the participant's diary. | 28 Days after vaccination 1 on Day 1 (Day 29) | 
| Number of Participants with Unsolicited AEs at 28 Days Post-vaccination 2 | Number of participants with unsolicited AEs at 28 days post-vaccination 2 will be reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Unsolicited AEs are all AEs for which the participant is not specifically questioned in the participant's diary. | 28 Days after vaccination 2 on Day 57 (Day 85) | 
| Number of Participants with Unsolicited AEs by Severity at 28 Days Post-vaccination 1 | Number of participants with unsolicited AEs by severity at 28 days post-vaccination 1 by severity will be reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Unsolicited AEs are all AEs for which the participant is not specifically questioned in the participant's diary. Severity will be assessed using FDA Toxicity grading scale which includes Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe) and Grade 4 (potentially life threatening). | 28 Days after vaccination 1 on Day 1 (Day 29) | 
| Number of Participants with Unsolicited AEs by Severity at 28 Days Post-vaccination 2 | Number of participants with unsolicited AEs by severity at 28 days post-vaccination 2 by severity will be reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Unsolicited AEs are all AEs for which the participant is not specifically questioned. Severity will be assessed using FDA Toxicity grading scale which includes Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe) and Grade 4 (potentially life threatening). | 28 Days after vaccination 2 on Day 57 (Day 85) | 
| Duration of Unsolicited AEs at 28 Days Post-vaccination 1 | Duration of unsolicited AEs at 28 days post-vaccination 1 will be reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Unsolicited AEs are all AEs for which the participant is not specifically questioned in the participant's diary. | 28 Days after vaccination 1 on Day 1 (Day 29) | 
| Duration of Unsolicited AEs at 28 Days Post-vaccination 2 | Duration of unsolicited AEs at 28 days post-vaccination 2 will be reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Unsolicited AEs are all AEs for which the participant is not specifically questioned in the participant's diary. | 28 Days after vaccination 2 on Day 57 (Day 85) | 
| Number of Participants with Unsolicited AEs Related to Study Vaccine at 28 Days Post-vaccination 1 | Number of participants with unsolicited AEs related to study vaccine at 28 days post-vaccination 1 will be reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Unsolicited AEs are all AEs for which the participant is not specifically questioned in the participant's diary. | 28 Days after vaccination 1 on Day 1 (Day 29) | 
| Number of Participants with Unsolicited AEs Related to Study Vaccine at 28 Days Post-vaccination 2 | Number of participants with unsolicited AEs related to study vaccine at 28 days post-vaccination 2 will be reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Unsolicited AEs are all AEs for which the participant is not specifically questioned in the participant's diary. | 28 Days after vaccination 2 on Day 57 (Day 85) | 
| Number of Participants with Serious Adverse Events (SAEs) | An SAE is any AE which results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a suspected transmission of any infectious agent via a medicinal product, or is medically important. | Day 1 up to Day 365 | 
| Number of Participants with Serious Adverse Events (SAEs) Related to Study Vaccine | An SAE is any AE which results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a suspected transmission of any infectious agent via a medicinal product, or is medically important. | Day 1 up to Day 365 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quantification of Antibody Binding to Hemagglutinin (HA) Stem or Full-length Hemagglutinin as Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | Antibodies targeting the stem domain of the influenza HA molecule will be quantified by ELISA using HA stem or full-length hemagglutinin antigens. | Days 1, 8, 29, 57, 64, 85, 238 and 365 |