A Trial to Evaluate Safety, Tolerability, and Immune Responses of an Investigational Monovalent Chimpanzee Adenoviral Vectored Sudan Ebolavirus Vaccine in Healthy Adults

A Phase 2, Randomized, Double-blind, Placebo-Controlled Trial to Evaluate Safety, Tolerability, and Immune Responses of an Investigational Monovalent Chimpanzee Adenoviral Vectored Sudan Ebolavirus Vaccine in Healthy Adults

This is a multi-center, double-blinded, placebo-controlled, Phase II study to evaluate safety, tolerability, and immunogenicity of a single dose of cAd3-Sudan vaccine in healthy adults up to 70 years of age. The study will enroll 200 eligible participants randomized 4:1 to receive the cAd3-Sudan vaccine at 1.0 × 10\^11 PU dose or placebo (0.9% sodium chloride (NaCl) solution) at Day 1, intramuscularly in deltoid muscle. Participants will be screened for eligibility up to 28 days before enrollment. Safety data will be periodically reviewed by an independent DSMB. Safety and immunogenicity will be assessed at Days 1, 8, 15, 29, 85, 169, and will conclude at the end of study visit on Day 366. PBMCs will be collected from a subset of 40 subjects on days 1, 15, 29, 169 and 366 to access cellular immunity.

Eligibility Criteria:
Inclusion Criteria:

1. Able and willing to complete and provide informed consent process prior to any trial procedure including optional consent for retention of blood samples for potential future testing and assay development.
2. Male or non-pregnant female 18 to 70 (inclusive) years of age at time of consent;
3. Is capable of understanding and agrees to comply with planned trial procedures and to be available for all clinic follow-up for all planned trial visits;
4. Able to provide proof of identity to the satisfaction of the trial clinician completing the enrollment process; has a means to be contacted and to contact the investigator during the trial;
5. Agree not to receive any vaccine within 3 months of trial vaccination (prior and after) trial;
6. Agree not to donate bone marrow, blood, or blood products until 3 months after the trial vaccination;
7. In good general health without clinically significant medical conditions, based on medical history, physical examination, vital signs, and clinical laboratory results as deemed acceptable by PI;
8. Clinical laboratory results within 28 days prior to vaccination within the testing laboratory reference ranges (or deemed not clinically significant by the PI) for the following parameters: White blood cells (WBC), Complete blood count (CBC), Red blood cells (RBC), Hemoglobin (HGB), total lymphocyte count, coagulation tests to include prothrombin time in terms of INR, fibrinogen, protein C, d-dimer, and chemistry tests to include alanine aminotransferase (ALT), aspartate aminotransferase (AST), and serum creatinine. A laboratory result that is outside the reference range and is deemed not clinically significant by the PI will not exclude the participant;
9. Has a body mass index (BMI) \&amp;gt;17 and ≤ 37 at screening.

   Female participant specific criteria:
10. Negative pregnancy serum test at screening, and negative urine pregnancy test before vaccination AND:
11. Use of oral, implantable, transdermal or injectable contraceptives for 21 days prior to vaccination and agree to use until trial end, UNLESS they fulfill one of the following criteria:

    1. At least 1 year post-menopausal.
    2. Surgically sterile.
    3. Use of another reliable form of contraception must be approved by the Investigator (e.g., double barrier method, intrauterine device, contraceptive patches).

    Male participants must agree:
12. Not to father a child or donate sperm through trial end;
13. To use an effective means of birth control from at least 21 days prior to vaccination through trial end after trial vaccination if assessed to be of reproductive potential.

Exclusion Criteria:

1. Participant is female and is breastfeeding or plans to become pregnant or breastfeed from trial vaccination through to trial end
2. Has any medical disease or condition that, in the opinion of the investigator, precludes trial participation. This includes any acute, subacute, intermittent, or chronic medical disease or condition that would place the Participant at an unacceptable risk of injury, render the Participant unable to meet the requirements of the protocol, or may interfere with the evaluation of responses or the Participants successful completion of the trial; (Chronic conditions that are well-controlled and medically stable, i.e. no relevant change in treatment for medical reasons occurred in the last 6 months, are allowed at the discretion of the PI, e.g. hypertension, asthma, thyroid disease) Any confirmed or suspected immunosuppressive or immunodeficient condition resulting from disease (e.g., malignancy, Human Immunodeficiency Virus \[HIV\] infection) or immunosuppressive/cytotoxic therapy (e.g., medications used during cancer chemotherapy, organ transplantation or to treat autoimmune disorders)
3. History of Guillain-Barré syndrome
4. History of allergy to any component of the vaccine
5. Serology screen positive for infectious diseases (hepatitis B, hepatitis C, HIV, Human T-cell leukemia virus (HTLV), Syphilis);
6. Known prior exposure to Sudan Ebolavirus or prior diagnosis of Sudan Ebolavirus Disease, determined from the participant's reported medical history
7. History of or active status of any of the following clinically significant conditions:

   1. Serious adverse reactions to vaccines such as anaphylaxis, urticaria (hives), respiratory difficulty, angioedema, or abdominal pain;
   2. Allergic reaction to excipients in the trial vaccine including gentamycin, neomycin or streptomycin;
   3. Diabetes mellitus Type I or Type II (even if stable)
   4. Tuberculosis
   5. Hereditary angioedema (HAE), acquired angioedema (AAE), or idiopathic forms of angioedema;
   6. Idiopathic urticaria within the last year
   7. Any malignancy, including non-skin melanoma, that has been active or treated, within 5 years prior to screening. (If diagnosed malignancy is 5 or more years prior to enrollment and cured with no ongoing treatment it will NOT be considered an exclusion);
   8. Seizure in the past 3 years or treatment for seizure disorder in the past 3 years (even if stable);
   9. Asplenia or functional asplenia;
   10. Any medical, psychiatric, social condition, occupational reason or other responsibility that, in the judgment of the investigator, is a contraindication to protocol participation or impairs a participant's ability to give informed consent;
8. Hematologic History:

   1. Bleeding disorder diagnosed by a doctor or use of anticoagulant medications such as, Warfarin, Apixaban, Dabigatran (e.g. factor deficiency, coagulopathy, or platelet disorder requiring special precautions) or significant bruising or bleeding difficulties with IM injections or blood draws;
   2. Family and personal history of bleeding or thrombosis or heparin-induced thrombocytopenia
   3. Conditions known to increase risk of thrombosis (e.g., pregnant or post-partum, extreme obesity, active malignancy or post-transplantation, recent surgery, immobility, recent infection, recent head trauma, autoimmune disease, inflammatory disease),
   4. Receipt of blood products within 3 months prior to enrollment.
   5. Has donated ≥ 450 mL of blood products within 30 days prior to randomization or expects to donate blood within 90 days of vaccine administration
   6. History of heparin-related thrombotic events, and/or receiving heparin treatments
9. Has a clinically significant acute illness (this does not include minor illnesses such as diarrhea or mild upper respiratory tract infection) or temperature ≥38.0° Celsius (≥100.4° Fahrenheit) within 24 hours of the planned dose of trial vaccine, rescreening and randomization at a later date is permitted at the discretion of the investigator and after consultation with the sponsor
10. Receipt of any of the following substances:

    1. prior receipt of Ebola or Marburg vaccine
    2. prior receipt of any adenoviral vectored vaccine, adenovirus-based or adeno-associated virus (AAV)-based gene therapies or treatments, including adenoviral COVID-19 vaccines or boosters.
    3. Participant received an investigational drug (including investigational drugs for prophylaxis of COVID-19) within 28 days of dosing or within washout period (5 half-lives) of such drug, or has used an invasive investigational medical device within 28 days of dosing
    4. received immunoglobulin (Ig) or monoclonal antibodies within 3 months,
    5. is currently enrolled or plans to participate in another investigational or interventional trial during the course of this trial (observational/registry trials are allowed)
11. Use of systemic corticosteroids in daily dose equivalence \&amp;gt; 20 mg of prednisolone in the last 90 days, and for periods exceeding 10 days. Non-steroidal anti-inflammatory drugs \[NSAIDS\] are permitted.
12. Current anti-tuberculosis prophylaxis or therapy