Clinical trial NCT02887482: GLS-5700 in Dengue Virus Seropositive Adults
Official title: Phase I, Placebo-Controlled, Double-Blind Study To Evaluate The Safety, Tolerability, AND Immunogenicity Of GLS-5700, Administered ID Followed By Electroporation In Dengue Virus-Seropositive Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Zika
Keywords: DNA
Vaccine
Lead sponsor: GeneOne Life Science, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Inovio Pharmaceuticals
First posted: 2016-09-02
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The clinical trial will assess the safety, tolerability, and immunogenicity of GLS-5700. GLS-5700 is a synthetic DNA plasmid vaccine against the Zika virus. This is a Phase 1 clinical trial of this vaccine which encodes for the premembrane-membrane and envelope regions of Zika virus.

Zika virus, first discovered in the Zika forest in 1947, has caused a large epidemic in South America, Central America, and the Caribbean islands commencing in late 2014 or early 2015. Zika virus can cause significant neurologic disease to include Guillain Barre Syndrome in adults and microcephaly and other birth defects among children born to mothers who are infected during pregnancy. At present no vaccines or treatments have been approved for Zika virus infection.

Detailed description: GLS-5700 contains a single plasmid containing DNA encoding for pre-membrane and envelope (prME) proteins of the Zika virus.

Eligibility criteria: Inclusion Criteria:

* Age 18-65 years;
* Able to provide consent to participate and having signed an Informed Consent Form (ICF);
* Able and willing to comply with all study procedures;
* Women of child-bearing potential agree to use medically effective contraception (oral contraception, barrier methods, spermicide, etc.) or have a partner who is sterile from enrollment to 3 months following the last injection, or have a partner who is medically unable to induce pregnancy.
* Sexually active men who are considered sexually fertile must agree to use either a barrier method of contraception during the study, and agree to continue the use for at least 3 months following the last injection, or have a partner who is permanently sterile or medically unable to become pregnant;
* Seropositive for dengue virus infection.
* Normal screening ECG or screening ECG with no clinically significant findings;
* Screening labs must be within normal limits or have only Grade 0-1 findings, except that creatinine may grade 2 at baseline;
* No history of clinically significant immunosuppressive or autoimmune disease.
* No history of dengue virus vaccination; no history of yellow fever vaccination
* Not currently or within the previous 4 weeks taking immunosuppressive agents (excluding inhaled, topical skin and/or eye drop-containing corticosteroids, low-dose methotrexate, or prednisone at a dose less than 10 mg/day, or steroid equivalent).

Exclusion Criteria:

* Administration of an investigational compound either currently or within 30 days of first dose;
* Previous receipt of an investigational product for the treatment or prevention of Zika virus infection except if subject is verified to have received placebo;
* Administration of any vaccine within 4 weeks of first dose;
* Administration of any monoclonal or polyclonal antibody product within 4 weeks of the first dose
* Administration of any blood product within 3 months of first dose;
* Pregnancy or breast feeding or have plans to become pregnant during the course of the study;
* Negative serologic result for dengue virus (any serotype) or history of receipt of either dengue virus or yellow fever virus vaccination at any time in the past;
* Positive serologic test for HIV, hepatitis B surface antigen (HBsAg); or any potentially communicable infectious disease as determined by the Principal Investigator or Medical Monitor;
* Positive serologic test for hepatitis C (exception: successful treatment with confirmation of sustained virologic response);
* Baseline evidence of kidney disease as measured by creatinine greater than 1.5 (CKD Stage II or greater);
* Baseline screening lab(s) with Grade 2 or higher abnormality;
* Chronic liver disease or cirrhosis;
* Immunosuppressive illness including hematologic malignancy, history of solid organ or bone marrow transplantation;
* Current or anticipated concomitant immunosuppressive therapy (excluding inhaled, topical skin and/or eye drop-containing corticosteroids, low-dose methotrexate, or prednisone at a dose equal to or greater than 10 mg/day, or steroid equivalent);
* Current or anticipated treatment with TNF-α inhibitors such as infliximab, adalimumab, etanercept;
* Prior major surgery or any radiation therapy within 4 weeks of group assignment;
* Any pre-excitation syndromes, e.g., Wolff-Parkinson-White syndrome;
* Presence of a cardiac pacemaker or automatic implantable cardioverter defibrillator (AICD)
* Metal implants within 20 cm of the planned site(s) of injection;
* Presence of keloid scar formation or hypertrophic scar as a clinically significant medical condition at the planned site(s) of injection.
* Prisoner or subjects who are compulsorily detained (involuntary incarceration) for treatment of either a physical or psychiatric illness;
* Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements or assessment of immunologic endpoints; or
* Not willing to allow storage and future use of samples for Zika virus related research
* Any illness or condition that in the opinion of the investigator may affect the safety of the subject or the evaluation of any study endpoint.

Primary outcomes:
measure: Mean change from baseline in safety laboratory measures
timeFrame: Day 0 through Week 14
measure: Incidence of solicited adverse events after vaccination
timeFrame: Day 0 through Week 14
measure: Incidence of unsolicited adverse events after vaccination
timeFrame: Day 0 through Week 14
measure: Incidence of serious adverse events
timeFrame: Day 0 through Week 14
Secondary outcomes:
measure: Binding antibody titers to Zika envelope
timeFrame: Day 0 through Week 60 following first dose
measure: Neutralizing antibody response against Zika virus
timeFrame: Day 0 through Week 60 following first dose
measure: T cell response
timeFrame: Day 0 through Week 60 following first dose
measure: Mean change from baseline for safety measures and adverse events
timeFrame: Day 0 through Week 60
Other outcomes:
Locations:
city: San Juan
country: Puerto Rico
facility: Clinical Research of Puerto Rico
city: San Juan
country: Puerto Rico
facility: Fundacion De Investigation
city: San Juan
country: Puerto Rico
facility: University of Puerto Rico
Study officials:
References: