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

Brief Title

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

Official 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

Brief Summary

      This is a multi-center, randomized, double-blinded, placebo-controlled, outpatient study.
      Recombinant deltaTM S Protein Severe Acute Respiratory Syndrome (SARS) Vaccine With and
      Without Aluminum Hydroxide Adjuvant (Provided through contract N01-AI-30023, manufactured by
      Protein Sciences Corporation), two doses, administered at 28 day interval. 1. S Protein
      Severe Acute Respiratory Syndrome (SARS) Vaccine without adjuvant: 5.0, 15.0 and 45.0 mcg per
      0.5 ml dose. 2. S Protein SARS Adjuvanted Vaccine: 5.0, 15.0 and 45.0 mcg per 0.5 ml dose.
      PLACEBO: diluents/placebo without vaccine (Phosphate Buffer Saline (PBS) with lower phosphate
      concentration). Approximately 84 healthy male and nonpregnant female subjects 18 to 40 years
      of age will be enrolled.
    

Detailed Description

      This is a Phase 1,multi-center, randomized, double-blinded, placebo-controlled, outpatient
      study in healthy male and nonpregnant female subjects 18 to 40 years of age, inclusive. Three
      dosing cohorts to investigate the safety, reactogenicity, and immunogenicity of Recombinant S
      protein Severe Acute Respiratory Syndrome (SARS) vaccine, with and without aluminum hydroxide
      adjuvant manufactured by Protein Sciences Corporation, administered intramuscularly on Days 0
      and 28 at a dose of 5, 15, or 45 mcg; controls will receive the diluents/placebo without
      vaccine. Approximately 84 subjects are expected to be enrolled. All subjects will receive 2
      doses of their assigned treatment via IM injection approximately 28 days apart, followed by
      assessments at 6, 12, 15, 18, 21 and 24 months after the second dose.
    

Study Phase

Phase 1

Study Type

Interventional


Primary Outcome

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

Secondary Outcome

 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)

Condition

SARS

Intervention

Aluminum hydroxide adjuvant (Alhydrogel®)

Study Arms / Comparison Groups

 Cohort 1
Description:  Recombinant S protein severe acute respiratory syndrome (SARS) vaccine received with aluminum hydroxide adjuvant (Alhydrogel®), without adjuvant, or placebo in 2 intramuscular doses, 28 days apart, at 5 micrograms per dose; 12 subjects receive unadjuvanted vaccine (SARS vaccine alone); 12 subjects receive adjuvanted vaccine {(SARS vaccine with aluminum hydroxide adjuvant (Alhydrogel®)}; 4 subjects receive placebo.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

0




Eligibility 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 from
             Southeast Asia or that were previously housed with Southeast Asian counterparts.
      

Gender

All

Ages

18 Years - 40 Years

Accepts Healthy Volunteers

Accepts Healthy Volunteers

Contacts

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Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT01376765

Organization ID

09-0100


Responsible Party

Sponsor

Study Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)


Study Sponsor

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Verification Date

April 2012