A Phase 1, First-In-Human Study of the Investigational COVID-19 Vaccine SC-Ad6-1 in Healthy Volunteers

Study Overview
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Brief Summary
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This is a single-centre, open-label, first-in-human, single ascending dose and multiple dose study to assess the safety, reactogenicity, and immunogenicity of the SC-Ad6-1 investigational product when administered via the intramuscular (IM), intranasal (IN) or inhaled (IH) route in healthy volunteers.

Official Title
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A Phase 1, First-In-Human, Open-label, Single Ascending Dose and Multidose Study to Assess the Safety, Reactogenicity, and Immunogenicity of the Adenovirus Vector SARS-CoV-2 Investigational Product SC-Ad6-1 Given Via Intramuscular, Intranasal or Inhaled Administration in Healthy Volunteers

Conditions
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Covid19

Intervention / Treatment
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* Biological: SC-Ad6-1
* Biological: SC-Ad6-1
* Biological: SC-Ad6-1


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Adult males and females, 18 to 60 years of age (inclusive) Body mass index ≥ 18.0 and ≤ 32.0 kg/m2, with a body weight ≥ 50 kg at screening Must have been fully vaccinated against COVID-19 and received last dose not less than 3 months prior to Day 1 (High Dose #3 I.M. and I.N. booster arms only), not less than 5 months prior to Day 1 (High Dose #4 I.N. booster arm only) and not less than 6 months prior to Day 1 (I.H. booster arms only) Key Exclusion Criteria: History or presence of significant cardiovascular, pulmonary, hepatic, renal, haematological, gastrointestinal, endocrine, immunologic, dermatologic or neurological disease History of chronic respiratory disorders including asthma, emphysema, interstitial lung disease, pulmonary hypertension, recurrent pneumonia, or recent (≤14 days prior to Screening) or ongoing respiratory tract infection History of thrombosis (e.g., deep vein thrombosis, pulmonary embolism, etc.), any coagulation dysregulation disorder, or a history of thrombosis noted in immediate family members History of any neurological disorders or seizures including Guillain-Barre syndrome, with the exception of febrile seizures during childhood Known previous infection with SARS-CoV-2 or presence of antibodies against SARS-CoV-2 or a positive SARS-CoV-2 PCR test (non-booster arms only) Any history of malignant disease ≤5 years prior to registration History of clinically relevant immunosuppression from, but not limited to, immunodeficiency conditions such as common variable hypogammaglobulinemia

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SC-Ad6-1 Low Dose Intramuscular<br>Low Dose SC-Ad6-1, I.M., single-dose (Day 1) | Biological: SC-Ad6-1<br>* SC-Ad6-1, I.M., single or multiple-dose<br>|
| Experimental: SC-Ad6-1 Medium Dose Intramuscular<br>Medium Dose SC-Ad6-1, I.M., single-dose (Day 1) | Biological: SC-Ad6-1<br>* SC-Ad6-1, I.M., single or multiple-dose<br>|
| Experimental: SC-Ad6-1 High Dose #1 Intramuscular<br>High Dose #1 SC-Ad6-1, I.M., single-dose (Day 1) | Biological: SC-Ad6-1<br>* SC-Ad6-1, I.M., single or multiple-dose<br>|
| Experimental: SC-Ad6-1 High Dose #2 Intramuscular<br>High Dose #2 SC-Ad6-1, I.M., single-dose (Day 1) | Biological: SC-Ad6-1<br>* SC-Ad6-1, I.M., single or multiple-dose<br>|
| Experimental: SC-Ad6-1 Multiple Dose Intramuscular<br>Multiple Dose SC-Ad6-1, I.M., multiple-dose (Day 1 and Day 22) | Biological: SC-Ad6-1<br>* SC-Ad6-1, I.M., single or multiple-dose<br>|
| Experimental: SC-Ad6-1 High Dose #3 Intramuscular Booster<br>High Dose #3 SC-Ad6-1, I.M., single-dose booster (Day 1) | Biological: SC-Ad6-1<br>* SC-Ad6-1, I.M., single or multiple-dose<br>|
| Experimental: SC-Ad6-1 Low Dose Intranasal<br>Low Dose SC-Ad6-1, I.N., single-dose (Day 1) | Biological: SC-Ad6-1<br>* SC-Ad6-1, I.N., single or multiple-dose<br>|
| Experimental: SC-Ad6-1 Medium Dose Intranasal<br>Medium Dose SC-Ad6-1, I.N., single-dose (Day 1) | Biological: SC-Ad6-1<br>* SC-Ad6-1, I.N., single or multiple-dose<br>|
| Experimental: SC-Ad6-1 High Dose #1 Intranasal<br>High Dose #1 SC-Ad6-1, I.N., single-dose (Day 1) | Biological: SC-Ad6-1<br>* SC-Ad6-1, I.N., single or multiple-dose<br>|
| Experimental: SC-Ad6-1 High Dose #2 Intranasal<br>High Dose #2 SC-Ad6-1, I.N., single-dose (Day 1) | Biological: SC-Ad6-1<br>* SC-Ad6-1, I.N., single or multiple-dose<br>|
| Experimental: SC-Ad6-1 Multiple Dose Intranasal<br>Multiple Dose SC-Ad6-1, I.N., multiple-dose (Day 1 and Day 22) | Biological: SC-Ad6-1<br>* SC-Ad6-1, I.N., single or multiple-dose<br>|
| Experimental: SC-Ad6-1 High Dose #3 Intranasal Booster<br>High Dose #3 SC-Ad6-1, I.N., single-dose booster (Day 1) | Biological: SC-Ad6-1<br>* SC-Ad6-1, I.N., single or multiple-dose<br>|
| Experimental: SC-Ad6-1 High Dose #4 Intranasal Booster<br>High Dose #4 SC-Ad6-1, I.N., single-dose booster (Day 1) | Biological: SC-Ad6-1<br>* SC-Ad6-1, I.N., single or multiple-dose<br>|
| Experimental: SC-Ad6-1 Low Dose Inhaled<br>Low Dose SC-Ad6-1, I.H., single-dose booster (Day 1) | Biological: SC-Ad6-1<br>* SC-Ad6-1, I.H., single or multiple-dose<br>|
| Experimental: SC-Ad6-1 Medium Dose Inhaled<br>Medium Dose SC-Ad6-1, I.H., single-dose booster (Day 1) | Biological: SC-Ad6-1<br>* SC-Ad6-1, I.H., single or multiple-dose<br>|
| Experimental: SC-Ad6-1 High Dose Inhaled<br>High Dose SC-Ad6-1, I.H., single-dose booster (Day 1) | Biological: SC-Ad6-1<br>* SC-Ad6-1, I.H., single or multiple-dose<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 and systemic adverse events for 7 days Following Each Dose | Solicited local adverse events are defined as pain, redness and swelling at the site of dose administration for the intramuscular arms, are defined as stuffy nose, runny nose, nasal discomfort, loss of smell, sore or scratchy throat for the intranasal arms and are defined as stuffy nose, runny nose, dry mouth, mouth sores, sore or scratchy throat and cough for the inhalation arms. Solicited systemic adverse events for all routes of administration are defined as fever, headache, muscle pain, joint pain, fatigue, nausea or vomiting, and chills. | 7 days following each dose | 
| Incidence and severity of adverse events (AEs), including withdrawals due to safety or tolerability reasons |  | Up to 106 days following first dose | 
| Humoral response to SARS-CoV-2 as measured by neutralizing antibodies using wild-type virus assay |  | Up to 106 days following first dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Humoral response to SARS-CoV-2 as measured by serum IgG and IgA antibodies to the SARS-CoV-2 spike protein (ELISA) |  | Up to 106 days following first dose | 
| Humoral response to SARS-CoV-2 as measured by mucosal IgA antibodies to the SARS-CoV-2 spike protein (ELISA) and total mucosal IgA |  | Up to 106 days following first dose | 
| Measurement of cytokine-producing T cells specific for the SARS-CoV-2 spike protein (ELISpot) |  | Up to 106 days following first dose | 
| Measurement of adenovirus 6 (Ad6) neutralizing antibodies (anti-drug antibodies (ADA)) |  | Up to 106 days following first dose |