Phase I Dose Escalation SARS-CoV Recombinant S Protein, With and Without Adjuvant, Vaccine Study

• Register: ClinicalTrials.gov
• Last refreshed on: 18 February 2013
• Main ID: NCT01376765
• Date of registration: 16/06/2011
• Primary sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Public title: Phase I Dose Escalation SARS-CoV Recombinant S Protein, With and Without Adjuvant, Vaccine Study
• Scientific title: Phase I, Double-Blinded, Placebo-Controlled, Dose- Escalation Study of the Safety and Immunogenicity of Recombinant SARS-CoV deltaTM S Protein Vaccine Formulated With and Without Alhydrogel® in Healthy Adults When Administered by the Intramuscular Route
• Date of first enrolment: June 2011
• Target sample size: 0
• Recruitment status: Withdrawn
• URL: http://clinicaltrials.gov/show/NCT01376765
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention

Countries of recruitment

United States

Key inclusion & exclusion criteria

Inclusion Criteria:

- Males or nonpregnant females between the ages of 18 and 40 years, inclusive.

- Women of childbearing potential (not surgically sterile via tubal ligation, bilateral
oophorectomy or hysterectomy or who have not been postmenopausal for >/=1 year) must
agree to practice adequate contraception for the 30-day period before vaccination
through 90 days after the second vaccination. Acceptable birth control methods for
the purposes of this study may include, but are not limited to, abstinence,
monogamous relationship with vasectomized partner, barrier methods such as condoms,
diaphragms, spermicides, and intrauterine devices, and licensed hormonal methods.

- In good health, as judged by the investigator and determined by vital signs
[temperature < 38 degrees C, heart rate 50 bpm, systolic blood
pressure 89 mmHg, diastolic blood pressure /= 60
mm Hg, respiratory rate >/= 12 breath per minute and < 17 breaths per minutes (see
toxicity table in Section 9.1.2)], medical history and a targeted physical
examination, as indicated, based on medical history.

- Screening laboratory values must be within normal limits. These include blood
hemoglobin, white blood cell (WBC) count, eosinophils, platelets, absolute
eosinophil, neutrophil, and lymphocyte cell counts, creatinine, aspartate
aminotransferase (AST), alanine transaminase (ALT), bilirubin (total), glucose
(random), and urinalysis (proteinuria and hematuria). See toxicity table in Section
9.1.3.2. Note: creatinine values lower than the normal are acceptable.

- Able to understand and comply with planned study procedures.

- Willing to be available for all study-required procedures, visits and calls for the
duration of the study.

- Provide written informed consent before initiation of any study procedures and be
available for all study visits.

- Negative for IgG antibodies to S protein of Severe Acute Respiratory Syndrome
coronavirus (SARS-CoV) measured by ELISA.

- Negative for antibodies to Human Immunodeficiency Virus (HIV) and hepatitis C virus
and for hepatitis B surface antigen.

- Negative for IgG antibodies to S protein of Severe Acute Respiratory Syndrome
coronavirus (SARS-CoV) measured by ELISA.

- Negative for antibodies to Human Immunodeficiency Virus (HIV) and hepatitis C virus
and for hepatitis B surface antigen.

Exclusion Criteria:

- A known allergy to components of the vaccine.

- A positive serum or urine pregnancy test within 24 hr prior to vaccination (if female
of childbearing potential as defined in Inclusion Criterion 2), women who are
planning to become pregnant from 30 days prior to entering the study until 90 days
after the final study vaccination, or women who are breastfeeding.

- Immunosuppression as result of underlying illness or treatment or use of anticancer
chemotherapy or radiation therapy (cytotoxic) within the preceding 36 months.

- An active neoplastic disease (excluding nonmelanoma skin cancer or prostate cancer
that is stable in the absence of therapy) or a history of any hematologic malignancy.
Nonactive neoplastic disease is defined as no neoplastic disease or treatment for
neoplastic disease within the past 5 years.

- A history of autoimmune disease (systemic lupus, rheumatoid arthritis, scleroderma,
polyarteritis, thyroiditis, etc).

- Used an immunosuppressive or immunomodulatory drug such as >0.5 mg/kg/day or >/=20 mg
total dose/day of prednisone orally or >800 mcg of inhaled beclomethasone for 2 or
more consecutive weeks within 6 months prior to the 1st vaccination. (Nasal and
topical steroids are allowed.)

- A known human immunodeficiency virus (HIV) infection, or active hepatitis B, or
hepatitis C virus infection.

- A diagnosis of schizophrenia, bipolar disease, or other major psychiatric diagnosis
in the past 3 years.

- Hospitalized for psychiatric illness, history of suicide attempt, or confinement for
danger to self or others in the past 3 years.

- Receiving psychiatric drugs listed below*. Subjects who are receiving a single
antidepressant drug and are stable for at least 3 months prior to enrollment, without
decompensating symptoms will be allowed to be enrolled in the study.

*aripiprazole, clozapine, ziprasidone, haloperidol, molindone, loxapine,
thioridazine, thiothixene, pimozide, fluphenazine, risperidone, mesoridazine,
quetiapine, trifluoperazine, trifluopromazine, chlorprothixene, chlorpromazine,
perphenazine, olanzapine, carbamazepine, divalproex sodium, lithium carbonate, or
lithium citrate.

- A history of receiving immunoglobulin or other blood product within the previous 3
months before vaccination.

- Received or plan to receive any live licensed vaccines within 4 weeks or inactivated
licensed vaccines within 2 weeks of each vaccination,

- An acute or chronic medical condition that, in the opinion of the investigator, would
render vaccination unsafe or would interfere with the evaluation of responses or is
not generally seen in healthy, normal subjects. (This includes, but is not limited
to, known cardiac disease, pulmonary disease, liver disease, renal disease, unstable
or progressive neurological disorders, diabetes mellitus, and transplant recipients.)

- A history of severe reactions following immunization with vaccines.

- Received an experimental agent (vaccine, drug, biologic, device, blood product, or
medication) within 1 month before vaccination in this study or expect to receive an
experimental agent during the 24-month study period.

- Any condition that would, in the opinion of the investigator, place them at an
unacceptable risk of injury, render them unable to meet the requirements of the
protocol, or that may interfere with successful completion of the study.

- A history of alcohol or drug abuse during the previous 1 year; for example, daily
excessive alcohol use or frequent binge drinking as determined by the investigator,
or chronic marijuana abuse or any other illicit drug use.

- Plans to travel outside North America in the time between the 1st vaccination and 56
days following the first vaccination or have plans to travel to Southeast Asia during
their entire study participation.

- Body temperature >/=100.4 F (>/=38.0 C) or acute illness within 3 days before
vaccination (subject may be rescheduled).

- Planned or have had a known exposure to the Himalayan palm civet, raccoon dog of
Southeast Asia, or Chinese horseshoe bat, including bats that have been shipped


Age minimum: 18 Years
Age maximum: 40 Years
Gender: Both

Health Condition(s) or Problem(s) studied

SARS

Intervention(s)

Biological: Recombinant S protein SARS vaccine

Drug: Aluminum hydroxide adjuvant (Alhydrogel®)

Other: Phosphate buffered saline Placebo

Primary Outcome(s)

Incidence of vaccine-related serious adverse events (SAEs) throughout the duration of the study. [Time Frame: Day 0 to Day 758]

Occurrence of laboratory abnormalities at 8 days after vaccination (Days 8 and 36) [Time Frame: 8 days after vaccination (Days 8 and 36)]

Occurrence of solicited local and systemic adverse events (AE)within 8 days after vaccination (Days 0-7 and Days 28-35) [Time Frame: 8 days after vaccination (Days 0-7 and Days 28-35)]

Secondary Outcome(s)

Comparison of rates of unsolicited AEs related to vaccine for all subjects between treatment groups and in the combined cohorts receiving vaccine with aluminum hydroxide adjuvant compared with those receiving vaccine with no adjuvant. [Time Frame: intervals from Days 0-7, Days 0-28, Days 8-28, Days 0-56, Days 29-36, and Days 29-56.]

Immunogenicity: Geometric Mean Titer (GMT) of antibody titers (IgG ELISA for S protein of SARS-CoV) 28 days after receipt of the second dose of vaccine (Day 56) at each vaccine dose level, with and without adjuvant [Time Frame: 28 days after receipt of the second dose of vaccine (Day 56)]

Immunogenicity: GMT of neutralizing antibody titers against SARS-CoV in each immunized group 28 days after receipt of the second dose of vaccine (Day 56). Measurement will include the Day 56 GMT and the mean fold change (GMT ratio Day 56:Day 0) [Time Frame: 28 days after receipt of the second dose of vaccine (Day 56)]

Immunogenicity: Proportion of subjects achieving a detectable serum neutralizing antibody titer against SARS-CoV in each immunized group 28 days after receipt of the second dose of vaccine (approximately Day 56) [Time Frame: 28 days after receipt of the second dose of vaccine (approximately Day 56)]

Secondary ID(s)

09-0100

Source(s) of Monetary Support

Please refer to primary and secondary sponsors