Phase 1 N=91 Randomized Double-blind Prevention

Phase I, Randomized, Double-blinded, Placebo-Controlled Dose De-escalation Study to Evaluate Safety and Immunogenicity of Alum Adjuvanted Zika Virus Purified Inactivated Vaccine (ZPIV) in Adults in a Flavivirus Endemic Area

Zika Virus Infection

Bottom Line

View on ClinicalTrials.gov: NCT03008122 ↗

Enrolled (actual)

Serious AEs

4.4%

Results posted

Apr 2023

Primary outcome: Primary: Frequency and Severity of Solicited Local Events Post Dose 1 by Treatment Group for All Participants — 15; 22; 10; 18 Participants

Study Design & Population

Study type: Interventional
Phase: Phase 1
Interventions: Placebo (Other); Zika Virus Purified Inactivated Vaccine (ZPIV) (Biological)
Age: Adult · 21+ yrs
Sex: All
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Primary completion: Aug 2021

Outcome Measures

Outcome	Result	p-value
PRIMARY Frequency and Severity of Solicited Local Events Post Dose 1 by Treatment Group for All Participants	15; 22; 10; 18; 22; 0	—
PRIMARY Frequency and Severity of Solicited Local Events Post Dose 2 by Treatment Group for All Participants	17; 33; 9; 15; 7; 0	—
PRIMARY Frequency and Severity of Solicited Local Events Post Dose 1 by Treatment Group for Baseline ZIKV Seropositive Participants	0; 1; 0; 1; 0; 0	—
PRIMARY Frequency and Severity of Solicited Local Events Post Dose 2 by Treatment Group for Baseline ZIKV Seropositive Participants	0; 1; 0; 1; 0; 0	—
PRIMARY Frequency and Severity of Solicited Local Events Post Dose 1 by Treatment Group for Baseline ZIKV Seronegative Participants	15; 21; 10; 17; 21; 0	—
PRIMARY Frequency and Severity of Solicited Local Events Post Dose 2 by Treatment Group for Baseline ZIKV Seronegative Participants	17; 32; 9; 14; 6; 0	—
PRIMARY Frequency and Severity of Solicited Local Events Post Dose 1 by Treatment Group for Baseline ZIKV Seropositive and DENV Seropositive Participants	0; 1; 0; 1; 0; 0	—
PRIMARY Frequency and Severity of Solicited Local Events Post Dose 2 by Treatment Group for Baseline ZIKV Seropositive and DENV Seropositive Participants	0; 1; 0; 1; 0; 0	—
PRIMARY Frequency and Severity of Solicited Local Events Post Dose 1 by Treatment Group for Baseline ZIKV Seropositive and DENV Seronegative Participants	—	—
PRIMARY Frequency and Severity of Solicited Local Events Post Dose 2 by Treatment Group for Baseline ZIKV Seropositive and DENV Seronegative Participants	—	—
PRIMARY Frequency and Severity of Solicited Local Events Post Dose 1 by Treatment Group for Baseline ZIKV Seronegative and DENV Seropositive Participants	10; 17; 9; 14; 15; 0	—
PRIMARY Frequency and Severity of Solicited Local Events Post Dose 2 by Treatment Group for Baseline ZIKV Seronegative and DENV Seropositive Participants	13; 25; 8; 10; 3; 0	—
PRIMARY Frequency and Severity of Solicited Local Events Post Dose 1 by Treatment Group for Baseline ZIKV Seronegative and DENV Seronegative Participants	5; 4; 1; 3; 6; 0	—
PRIMARY Frequency and Severity of Solicited Local Events Post Dose 2 by Treatment Group for Baseline ZIKV Seronegative and DENV Seronegative Participants	4; 7; 1; 4; 3; 0	—
PRIMARY Frequency and Severity of Solicited Systemic Events Post Dose 1 by Treatment Group for All Participants	21; 25; 5; 11; 17; 4	—
PRIMARY Frequency and Severity of Solicited Systemic Events Post Dose 2 by Treatment Group for All Participants	26; 36; 8; 5; 5; 1	—
PRIMARY Frequency and Severity of Solicited Systemic Events Post Dose 1 by Treatment Group for Baseline ZIKV Seropositive Participants	0; 1; 0; 1; 0; 0	—
PRIMARY Frequency and Severity of Solicited Systemic Events Post Dose 2 by Treatment Group for Baseline ZIKV Seropositive Participants	1; 1; 0; 0; 0; 0	—
PRIMARY Frequency and Severity of Solicited Systemic Events Post Dose 1 by Treatment Group for Baseline ZIKV Seronegative Participants	21; 24; 5; 10; 17; 4	—
PRIMARY Frequency and Severity of Solicited Systemic Events Post Dose 2 by Treatment Group for Baseline ZIKV Seronegative Participants	25; 35; 8; 5; 4; 1	—
PRIMARY Frequency and Severity of Solicited Systemic Events Post Dose 1 by Treatment Group for Baseline ZIKV Seropositive and DENV Seropositive Participants	0; 1; 0; 1; 0; 0	—
PRIMARY Frequency and Severity of Solicited Systemic Events Post Dose 2 by Treatment Group for Baseline ZIKV Seropositive and DENV Seropositive Participants	1; 1; 0; 0; 0; 0	—
PRIMARY Frequency and Severity of Solicited Systemic Events Post Dose 1 by Treatment Group for Baseline ZIKV Seropositive and DENV Seronegative Participants	—	—
PRIMARY Frequency and Severity of Solicited Systemic Events Post Dose 2 by Treatment Group for Baseline ZIKV Seropositive and DENV Seronegative Participants	—	—
PRIMARY Frequency and Severity of Solicited Systemic Events Post Dose 1 by Treatment Group for Baseline ZIKV Seronegative and DENV Seropositive Participants	17; 18; 5; 7; 13; 3	—
PRIMARY Frequency and Severity of Solicited Systemic Events Post Dose 2 by Treatment Group for Baseline ZIKV Seronegative and DENV Seropositive Participants	19; 27; 8; 3; 3; 0	—
PRIMARY Frequency and Severity of Solicited Systemic Events Post Dose 1 by Treatment Group for Baseline ZIKV Seronegative and DENV Seronegative Participants	4; 6; 0; 3; 4; 1	—
PRIMARY Frequency and Severity of Solicited Systemic Events Post Dose 2 by Treatment Group for Baseline ZIKV Seronegative and DENV Seronegative Participants	6; 8; 0; 2; 1; 1	—
PRIMARY Frequency and Severity of Unsolicited Adverse Events by Treatment Group for All Participants	21; 27; 5; 6; 12; 0	—
PRIMARY Frequency and Severity of Unsolicited Adverse Events by Treatment Group for Baseline ZIKV Seropositive Participants	0; 0; 0; 1; 0; 0	—
PRIMARY Frequency and Severity of Unsolicited Adverse Events by Treatment Group for Baseline ZIKV Seronegative Participants	21; 26; 5; 5; 11; 0	—
PRIMARY Frequency and Severity of Unsolicited Adverse Events by Treatment Group for Baseline ZIKV Seropositive and DENV Seropositive Participants	0; 0; 0; 1; 0; 0	—
PRIMARY Frequency and Severity of Unsolicited Adverse Events by Treatment Group for Baseline ZIKV Seropositive and DENV Seronegative Participants	—	—
PRIMARY Frequency and Severity of Unsolicited Adverse Events by Treatment Group for Baseline ZIKV Seronegative and DENV Seropositive Participants	16; 21; 4; 4; 9; 0	—
PRIMARY Frequency and Severity of Unsolicited Adverse Events by Treatment Group for Baseline ZIKV Seronegative and DENV Seronegative Participants	5; 5; 1; 1; 2; 0	—
PRIMARY Frequency and Type of Serious Adverse Events (SAE) Considered Related to Study Vaccine for All Participants	0; 0; 0	—
PRIMARY Duration of Serious Adverse Events (SAE) Considered Related to Study Vaccine for All Participants	0; 0; 0	—
PRIMARY Frequency and Type of Adverse Events of Special Interest (AESI) Considered Related to Study Vaccine for All Participants	0; 0; 0	—
PRIMARY Duration of Adverse Events of Special Interest (AESI) Considered Related to Study Vaccine for All Participants	—	—
PRIMARY Frequency of New Onset Chronic Medical Conditions for All Participants	1; 0; 0; 0; 0; 0	—
PRIMARY Comparison of Frequency and Type of Vaccine-related Grade 3 Local, Systemic, or Laboratory AE, and Grade 2 or Greater Local or Systemic Reactogenicity Post Dose 1 for All Participants	0; 0; 0; 4; 4; 1	—
PRIMARY Comparison of the Frequency and Type of Vaccine-related Grade 3 Local, Systemic, or Laboratory AE, and Grade 2 or Greater Local or Systemic Reactogenicity Post Dose 2 for All Participants	0; 0; 0; 1; 5; 0	—
PRIMARY Comparison of the Frequency and Type of Vaccine-related Grade 3 Local, Systemic, or Laboratory AE, and Grade 2 or Greater Local or Systemic Reactogenicity Post Dose 1 for Baseline ZIKV Seropositive Participants	0; 0; 0; 0	—
PRIMARY Comparison of the Frequency and Type of Vaccine-related Grade 3 Local, Systemic, or Laboratory AE, and Grade 2 or Greater Local or Systemic Reactogenicity Post Dose 2 for Baseline ZIKV Seropositive Participants	0; 0; 0; 0	—
PRIMARY Comparison of the Frequency and Type of Vaccine-related Grade 3 Local, Systemic, or Laboratory AE, and Grade 2 or Greater Local or Systemic Reactogenicity Post Dose 1 for Baseline ZIKV Seronegative Participants	0; 0; 0; 4; 3; 1	—
PRIMARY Comparison of the Frequency and Type of Vaccine-related Grade 3 Local, Systemic, or Laboratory AE, and Grade 2 or Greater Local or Systemic Reactogenicity Post Dose 2 for Baseline ZIKV Seronegative Participants	0; 0; 0; 1; 5; 0	—
PRIMARY Comparison of the Frequency and Type of Vaccine-related Grade 3 Local, Systemic, or Laboratory AE, and Grade 2 or Greater Local or Systemic Reactogenicity Post Dose 1 for Baseline ZIKV Seropositive and DENV Seropositive Participants	0; 0; 0; 0	—
PRIMARY Comparison of the Frequency and Type of Vaccine-related Grade 3 Local, Systemic, or Laboratory AE, and Grade 2 or Greater Local or Systemic Reactogenicity Post Dose 2 for Baseline ZIKV Seropositive and DENV Seropositive Participants	0; 0; 0; 0	—
PRIMARY Comparison of the Frequency, Type, and Duration of Vaccine-related Grade 3 Local, Systemic, or Laboratory AE, and Grade 2 or Greater Local or Systemic Reactogenicity Post Dose 1 for Baseline ZIKV Seropositive and DENV Seronegative Participants	—	—
PRIMARY Comparison of the Frequency, Type, and Duration of Vaccine-related Grade 3 Local, Systemic, or Laboratory AE, and Grade 2 or Greater Local or Systemic Reactogenicity Post Dose 2 for Baseline ZIKV Seropositive and DENV Seronegative Participants	—	—
PRIMARY Comparison of the Frequency and Type of Vaccine-related Grade 3 Local, Systemic, or Laboratory AE, and Grade 2 or Greater Local or Systemic Reactogenicity Post Dose 1 for Baseline ZIKV Seronegative and DENV Seropositive Participants	0; 0; 0; 3; 3; 1	—
PRIMARY Comparison of the Frequency and Type of Vaccine-related Grade 3 Local, Systemic, or Laboratory AE, and Grade 2 or Greater Local or Systemic Reactogenicity Post Dose 2 for Baseline ZIKV Seronegative and DENV Seropositive Participants	0; 0; 0; 1; 4; 0	—
PRIMARY Comparison of the Frequency and Type of Vaccine-related Grade 3 Local, Systemic, or Laboratory AE, and Grade 2 or Greater Local or Systemic Reactogenicity Post Dose 1 for Baseline ZIKV Seronegative and DENV Seronegative Participants	0; 0; 0; 1; 0; 0	—
PRIMARY Comparison of the Frequency and Type of Vaccine-related Grade 3 Local, Systemic, or Laboratory AE, and Grade 2 or Greater Local or Systemic Reactogenicity Post Dose 2 for Baseline ZIKV Seronegative and DENV Seronegative Participants	0; 0; 0; 0; 1; 0	—
PRIMARY Comparison of the Duration and Type of Vaccine-related Grade 3 Local, Systemic, or Laboratory AE, and Grade 2 or Greater Local or Systemic Reactogenicity Post Dose 1 for All Participants	2.5; 2; 1.5; 1; 4; 1	—
PRIMARY Comparison of the Duration and Type of Vaccine-related Grade 3 Local, Systemic, or Laboratory AE, and Grade 2 or Greater Local or Systemic Reactogenicity Post Dose 2 for All Participants	1; 2; 5.5; 7.5; 1; 3	—
PRIMARY Comparison of the Duration and Type of Vaccine-related Grade 3 Local, Systemic, or Laboratory AE, and Grade 2 or Greater Local or Systemic Reactogenicity Post Dose 1 for Baseline ZIKV Seropositive Participants	—	—
PRIMARY Comparison of the Duration and Type of Vaccine-related Grade 3 Local, Systemic, or Laboratory AE, and Grade 2 or Greater Local or Systemic Reactogenicity Post Dose 2 for Baseline ZIKV Seropositive Participants	—	—
PRIMARY Comparison of the Duration and Type of Vaccine-related Grade 3 Local, Systemic, or Laboratory AE, and Grade 2 or Greater Local or Systemic Reactogenicity Post Dose 1 for Baseline ZIKV Seronegative Participants	2.5; 2; 1.5; 1; 4; 1	—
PRIMARY Comparison of the Duration and Type of Vaccine-related Grade 3 Local, Systemic, or Laboratory AE, and Grade 2 or Greater Local or Systemic Reactogenicity Post Dose 2 for Baseline ZIKV Seronegative Participants	1; 2; 5.5; 7.5; 1; 3	—
PRIMARY Comparison of the Duration and Type of Vaccine-related Grade 3 Local, Systemic, or Laboratory AE, and Grade 2 or Greater Local or Systemic Reactogenicity Post Dose 1 for Baseline ZIKV Seropositive and DENV Seropositive Participants	—	—
PRIMARY Comparison of the Duration and Type of Vaccine-related Grade 3 Local, Systemic, or Laboratory AE, and Grade 2 or Greater Local or Systemic Reactogenicity Post Dose 2 for Baseline ZIKV Seropositive and DENV Seropositive Participants	—	—
PRIMARY Comparison of the Duration and Type of Vaccine-related Grade 3 Local, Systemic, or Laboratory AE, and Grade 2 or Greater Local or Systemic Reactogenicity Post Dose 1 for Baseline ZIKV Seronegative and DENV Seropositive Participants	2; 2; 1.5; 1; 1; 3	—
PRIMARY Comparison of the Duration and Type Duration of Vaccine-related Grade 3 Local, Systemic, or Laboratory AE, and Grade 2 or Greater Local or Systemic Reactogenicity Post Dose 2 for Baseline ZIKV Seronegative and DENV Seropositive Participants	1; 2; 1; 11; 1; 2	—
PRIMARY Comparison of the Duration and Type of Vaccine-related Grade 3 Local, Systemic, or Laboratory AE, and Grade 2 or Greater Local or Systemic Reactogenicity Post Dose 1 for Baseline ZIKV Seronegative and DENV Seronegative Participants	4; 4	—
PRIMARY Comparison of the Duration and Type of Vaccine-related Grade 3 Local, Systemic, or Laboratory AE, and Grade 2 or Greater Local or Systemic Reactogenicity Post Dose 2 for Baseline ZIKV Seronegative and DENV Seronegative Participants	3.5; 10; 4; 1; 3; 10	—
PRIMARY Comparison of Study Withdrawals and Discontinuation of Study Vaccination Due to Any Reason for All Participants	10; 13; 4; 3; 2; 1	—
PRIMARY Comparison of Study Withdrawals and Discontinuation of Study Vaccination Due to Any Reason for Baseline ZIKV Seropositive Participants	0; 1; 0; 0; 0; 0	—
PRIMARY Comparison of Study Withdrawals and Discontinuation of Study Vaccination Due to Any Reason for Baseline ZIKV Seronegative Participants	9; 12; 4; 3; 2; 1	—
PRIMARY Comparison of Study Withdrawals and Discontinuation of Study Vaccination Due to Any Reason for Baseline ZIKV Seropositive and DENV Seropositive Participants	0; 1; 0; 0; 0; 0	—
PRIMARY Comparison of Study Withdrawals and Discontinuation of Study Vaccination Due to Any Reason for Baseline ZIKV Seropositive and DENV Seronegative Participants	—	—
PRIMARY Comparison of Study Withdrawals and Discontinuation of Study Vaccination Due to Any Reason for Baseline ZIKV Seronegative and DENV Seropositive Participants	7; 10; 4; 3; 2; 1	—
PRIMARY Comparison of Study Withdrawals and Discontinuation of Study Vaccination Due to Any Reason for Baseline ZIKV Seronegative and DENV Seronegative Participants	2; 2; 0; 0; 0; 0	—

Summary

This study is randomized, double-blinded, placebo-controlled, Phase 1, dose de-escalation study to evaluate the safety, reactogenicity, and immunogenicity of Alum Adjuvanted Zika Virus Purified Inactivated Vaccine (ZPIV) administered to healthy male and non-pregnant female adult subjects. This study will enroll 90 healthy male and non-pregnant female subjects between the ages of 21 and 49 and will be conducted at Ponce Medical School Foundation, Inc.-CAIMED in Ponce, Puerto Rico. The duration of each subject's participation is approximately 26 months from recruitment through the last study visit. The entire study is expected to take approximately 49 months to complete. Two dose levels will be evaluated. Each subject will receive either placebo or 5 mcg (Group 1) or 2.5 mcg (Group 2) of ZPIV administered by intramuscular (IM) injection on Days 1 and 29. Solicited local and systemic reactogenicity data will be collected from all subjects through Day 8 after each vaccination. All subjects will be monitored for occurrence of unsolicited adverse events until 28 days after the second vaccination. The study will consist of a screening period of up to 28 days, a vaccination period in which subjects will receive a prime dose of vaccine on Day 1 followed by a boost on Day 29, and a follow-up period of 24 months post boost vaccination. Primary objectives are: 1) Assess the safety and reactogenicity of a homologous prime boost regimen of ZPIV given at two different dose levels. 2) Compare the safety and reactogenicity of ZPIV after each vaccination, between dosage groups, and by pre-vaccination flavivirus immune status.

Eligibility Criteria

Inclusion Criteria

Must be a male or non-pregnant, non-breastfeeding female between the age of 21 and 49 years, inclusive at the time of screening and enrollment.
Must be willing and able to read, sign and date the informed consent document before study related procedures are performed.
Must be willing and able to comply with study requirements and available for follow-up visits for the entire study.
Must have a means to be contacted by telephone.
Must have a body mass index (BMI) > /= 18.1 and /= 11.5 g/dL; men > /= 13.5 g/dL
Hemotocrit: women: > /= 34.5%; men > /= 40.5%
White blood cell count: > /= 3.500 cells/mm3 but /= 150,000 but /= 3 months have passed since sterilization procedure. Postmenopausal is defined as amenorrhea for > /= 12 months without an alternative medical cause. Permanent female sterilization procedures include tubal ligation, bilateral salpingectomy, hysterectomy, bilateral oophorectomy, or successful Essure placement.
Women of childbearing potential must use an acceptable method of contraception* from one month (30 days) prior to the first vaccination until the end of the study.

*Acceptable methods of contraception include the following:

Use highly effective contraceptive methods, defined by /= 3 months prior to first vaccination, OR
Practice abstinence defined as refraining from heterosexual intercourse from 30 days before first vaccination until the end of the study.
Female subjects must agree to not donate eggs (ova, oocytes) from the start of screening period until the end of the study.
Subjects must provide concurrent consent at the time of enrollment and 1st vaccination to future use of stored blood samples to measure immunity to ZIKV.

Exclusion Criteria

Has plans to become pregnant during the course of the study, or is currently pregnant or breastfeeding.
Plans to receive a licensed flavivirus vaccine or participate in another flavivirus vaccine trial during the study.
Has positive serology for HIV 1/2, Hepatitis C virus, or Hepatitis B surface antigen.
Has known or suspected congenital or acquired immunodeficiency, or recent history or current use of immunosuppressive therapy* *Anti-cancer chemotherapy or radiation therapy within the preceding 6 months, or long-term (at least 2 weeks within the previous 3 months) systemic corticosteroids therapy (at a dose of at least 0.5 mg/kg/day). Intranasal or topical prednisone (or equivalent) is allowed.
Had organ and/or stem cell transplantation whether or not on chronic immunosuppressive therapy.
Has history of malignancy other than squamous cell or basal cell skin cancer, unless there has been surgical excision that is considered to have achieved cure*.

*Subjects with a history of skin cancer must not be vaccinated at the previous tumor site.

Has history of chronic or acute severe neurologic condition*.

*Including history of Guillain-Barre syndrome, seizure disorder or epilepsy, Bell's palsy, meningitis, or disease with any focal neurologic deficits.

Has diabetes mellitus type 1 or type 2, including cases controlled with diet alone.

*Note: history of isolated gestational diabetes is not an exclusion criterion.

Has history of thyroidectomy, or thyroid disease requiring medication during the last 12 months.
Has major psychiatric illness during last 12 months that in the investigator's opinion would preclude participation.
Has history of other chronic disease or condition*.

*Includes the conditions and diagnoses defined as AESI in section 9, as well as autoimmune disease, hypercholesterolemia, chronic hepatitis or cirrhosis, chronic pulmonary disease, chronic renal disease, and chronic cardiac disease including hypertension even if medically controlled

Vital signs must be normal by protocol toxicity grading scale or determined to be normal-variant by investigator. In the event of an abnormal heart rate or blood pressure due to physiological variation or activity, the subject

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Data sourced from ClinicalTrials.gov (NCT03008122). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.