In humans, Sudan Ebolavirus (SUDV) is responsible for causing Sudan Ebolavirus Disease (SUVD), formerly known as Ebola hemorrhagic fever. It spreads through human-to-human transmission, with infection resulting from direct contact with blood, secretions, organs, or other bodily fluids of infected people, and indirect contact with contaminated environments. The average case fatality rate of SUVD is around 50%.

SUDV has an incubation period of 2 to 21 days followed by a rapid and abrupt onset of nonspecific symptoms such as fever, extreme fatigue, gastrointestinal complaints, abdominal pain, anorexia, headache, myalgias, and/or arthralgias, and diarrhea that can persist for a week. Many patients develop severe hemorrhagic manifestations, including hemorrhagic rash, epistaxis, mucosal bleeding, hematuria, hemoptysis, hematemesis, melena, conjunctival hemorrhage, tachypnea, confusion, somnolence, and hearing loss between 5 and 7 days after infection. The SUDV has been associated with 8 major outbreaks, mainly in Africa. There is a continued potential threat of spread to other countries given the frequency of international travel.

As there are currently no approved vaccines or therapeutics to treat individuals infected with SUDV, a vaccine with rapid and durable protective immunity would be desirable for populations in areas of the world where outbreaks occur sporadically.

The primary goal of the cAd3-EBO S vaccine development program is to create a safe and effacacious vaccine that can induce rapid immunity followed by durable protection against SUVD. Sabin cAd3-EBO S vaccine is supplied as a single-dose vial that contains a recombinant chimpanzee adenovirus Type 3 (cAd3) vector that expresses wild-type (WT) glycoprotein (GP) from the Gulu strain of the SUDV.

Previous studies have evaluated the safety and immunogenicity of the cAd3-EBO S vaccine in a small group of healthy adults up to 50 years of age in the United States. This Phase 2 study will evaluate the safety, tolerability, and immunogenicity of the cAd3-EBO S vaccine in healthy adults up to 70 years of age in an African population.

Sudan ebolavirus (SUDV) is one of the 6 genera in the family Filoviridae, which, along with Marburgvirus and Cuevavirus, are known to induce viral hemorrhagic fever. SUDV is a large, negative-strand RNA virus composed of 7 genes encoding viral proteins, including a single glycoprotein (GP). In humans, SUDV is responsible for causing Sudan Ebolavirus Disease (SUVD). It spreads through human-to-human transmission, with infection resulting from direct contact with blood, secretions, organs, or other bodily fluids of infected people and indirect contact with contaminated environments. SUVD has an incubation period of 2 to 21 days followed by a rapid and abrupt onset of nonspecific symptoms such as fever, extreme fatigue, gastrointestinal complaints, abdominal pain, anorexia, headache, myalgias, and/or arthralgias, and diarrhea can persist for a week. Many patients develop severe hemorrhagic manifestations, including hemorrhagic rash, epistaxis, mucosal bleeding, hematuria, hemoptysis, hematemesis, melena, conjunctival hemorrhage, tachypnea, confusion, somnolence, and hearing loss between 5 and 7 days after infection. Laboratory findings include low white blood cell and platelet counts and elevated liver enzymes. In the last decades, SUDV has been associated with large outbreaks of SUVD in Africa; the average case fatality rate is around 50%, varying from 41% to 71% depending on virus strain and case management (WHO 2021).

The SUDV is the etiologic agent of SUVD and has been associated with 8 major outbreaks; the 2 largest occurring in Africa (Sudan in 1976 and Uganda in 2000) that resulted in case fatality rates over 53%. The first recorded case of SUVD in Uganda occurred in August 2000 and resulted in 224 fatalities. (WHO 2022) Recently 55 fatal cases of SUVD were reported from several regions in Uganda as of January 2023 (WHO 2023). There is a continued potential threat of spread to other countries given the frequency of international travel (IB 2023).

The primary goal of the cAd3-EBO S vaccine development program is to create a safe and effacacious vaccine that can induce rapid immunity followed by durable protection against SUVD. Sabin cAd3-EBO S vaccine is supplied as a single-dose vial that contains a recombinant chimpanzee adenovirus Type 3 (cAd3) vector that expresses wild-type (WT) GP from the Gulu strain of the SUDV.

The cAd3 vector was selected as it has little to no pre-existing immunity in human populations, its superior immunogenicity in humans relative to DNA vaccines for other viral diseases, and its performance in Non-Human Primate (NHP) Ebolavirus challenge studies. A Phase 1 study (RV508) evaluated the safety, tolerability, and immunogenicity of the SUDV chimpanzee adenovirus vector vaccine, VRC-EBOADC086-00-PU (cAd3-EBO S), in healthy adults at the Makerere University Walter Reed Project in Kampala, Uganda. Tachypnoea was the most commonly reported unsolicited AE, occurring in 12 of 40 subjects (30%). Overall, the cAd3-EBO S vaccine was well-tolerated. There were no deaths or SAEs related to the product (NCT04041570). Further, a Phase 1 study (Sabin-001) evaluated the safety, tolerability, and immunogenicity of cAd3-EBO S in healthy adults at the Oklahoma Blood Institute in Oklahoma City, Oklahoma. A total of 14 unsolicited adverse events were reported by 9 of 16 (56.3%) subjects, of which 4 (28.6%) events were assessed related to study product administration. Related events included one subject who developed a feeling of body temperature change (mild) and fatigue. One subject reported moderate malaise and another subject developed mild lymphadenopathy. All related events resolved within 3 days and without sequalae. There were no deaths or Serious Adverse Events (SAEs) related to the product (NCT04723602).

Similarly, a Phase 1, dose-escalation, open-label study of cAd3-EBO S conducted at the National Institutes of Health (NIH) Clinical Center in Bethesda, Maryland supported the safety and immunogenicity of a single vaccination. The rates and severity of local and systemic side effects, including fever at higher dose levels, were similar to those observed in previous studies of other adenovirus vectors (Ledgerwood 2017). A Phase 2 randomized, observer-blind, placebo-controlled study on the safety, reactogenicity, and immunogenicity of a chimpanzee adenovirus vectored Ebola vaccine in adults conducted at multiple investigational sites in Bamenda and Yaounde, Cameroon, Bamako, Mali, Abuja, Nigeria, and Dakar, Senegal showed it was immunogenic and well tolerated in adults (Tapia 2020).

Moreover, chimpanzee adenoviral vector vaccines targeting other diseases have been generally safe in healthy adults at dosages up to 1 × 10¹¹ Viral Particles (VP) per injection in completed and ongoing clinical trials. Systemic reactogenicity typically occurs on the day of or day after vaccination and may include headache, malaise, myalgia, chills, and fever. When present, fever onset occurs within 1 day of vaccination and typically resolves within 24 hours of onset. A pattern of fever occurring later than 1 day after vaccination or lasting longer than 1 day may require evaluation for additional etiology (Ledgerwood 2017). Risks of the vaccine to pregnant and nursing women and to the unborn fetus are unknown. As such, women of reproductive potential will be required to agree to use birth control beginning at least 21 days prior to enrollment and continue through 24 weeks after study vaccination. There may be other unknown side effects. Blood drawing with needles, like injections, may cause pain, bruising, feeling lightheaded, fainting, possible nerve injury and, rarely, infection at the site where the blood is taken.

Although study participants may benefit from clinical evaluations, laboratory testing and physical examinations (during assessment of eligibility), study participants will receive no direct benefit from participation.

Detailed information about the known and expected benefits and risks and reasonably expected Adverse Events (AEs) of the Investigational Product (IP) is provided in the investigator’s brochure (IB 2023).