Clinical trial NCT02304185: Safety, Tolerability and Immunogenicity Study of 2 Dose Levels of Trimeric Glycoprotein140 (gp140) in Healthy Adult Volunteers
Official title: A First in Human Study to Evaluate the Safety, Tolerability and Immunogenicity of Two Dose Levels of Trimeric gp140 Protein in Healthy Adult Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Healthy
Acquired Immuno-Deficiency Syndrome
Acquired Immunodeficiency Syndrome Virus
Glycoprotein
Adjuvant
Vaccine
Placebo
Lead sponsor: Crucell Holland BV
Sponsor class: INDUSTRY
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
name: Beth Israel Deaconess Medical Center
First posted: 2014-12-01
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to assess the safety and tolerability of 2 different dose levels of trimeric glycoprotein140 (gp140) administered as a 2-dosage regimen, intramuscularly (injection of a substance into a muscle), with and without aluminum phosphate as adjuvant in healthy human immunodeficiency virus (HIV)-uninfected participants.

Detailed description: This is a single-center, randomized (the study drug is assigned by chance), placebo-controlled (study in which the experimental treatment or procedure is compared to a pretend treatment with no drug in it to test if the drug has a real effect), and double-blind (neither physician nor participant knows the treatment that the participant receives) study. The study comprises a Screening Period (up to 4 weeks), a Vaccination Period (participants will be vaccinated on Days 1 and 29), and a Follow-up Period (up to 48 weeks). All eligible participants will be randomly assigned to 1 of the 2 sequential cohorts (low dose cohort and high dose cohort). Participants in low dose cohort will receive 1 of the following treatments: low dose (50 microgram \[mcg\]) gp140 drug product (DP), low dose gp140 DP with adjuvant (aluminum phosphate), placebo matched to low dose DP; and participants in high dose cohort will receive 1 of the following treatments: high dose (250 mcg) gp140 DP, high dose gp140 DP with adjuvant, and placebo matched to high dose DP. There will be an interim safety review of safety/tolerability from low-dose cohort before the high-dose cohort receives study treatment. Total study duration will be 56 weeks per participant. Participants' safety will be monitored throughout the study.

Eligibility criteria: Inclusion Criteria:

* Participant must be healthy on the basis of physical examination, medical history, electrocardiogram (ECG), laboratory criteria, and vital signs measurement performed at Screening
* Participants are negative for human immunodeficiency virus (HIV) infection at Screening (negative United States Food and Drug Administration-approved HIV diagnostic blood test)
* All female participants of childbearing potential must have a negative serum (beta human chorionic gonadotropin) at Screening, and a negative urine pregnancy test pre-dose on Day 1 and Day 29
* A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction until 3 months after receiving the last dose of study vaccine. A man must agree not to donate sperm until 3 months after receiving the last dose of study vaccine
* Participants are assessed by the clinic staff as being at low risk for HIV infection

Exclusion Criteria:

* Participant has chronic active hepatitis B or active hepatitis C, active syphilis infection, chlamydia, gonorrhea, or trichomonas. Active syphilis documented by exam or serology unless positive serology is due to past treated infection
* In the 12 months prior to enrollment, participant has a history of newly acquired syphilis, gonorrhea, non-gonococcal urethritis, herpes simplex virus type 2 (HSV2), chlamydia, pelvic inflammatory disease, trichomonas, mucopurulent cervicitis, epididymitis, proctitis, lymphogranulomavenereum, chancroid, or hepatitis B
* Participant has any clinically significant acute or chronic medical condition that in the opinion of the Investigator would preclude participation (for example, history of seizure disorders, bleeding/clotting disorder, autoimmune disease, active malignancy, poorly controlled asthma, active tuberculosis or other systemic infections)
* Participant has had major surgery within the 4 weeks prior to study entry or planned major surgery through the course of the study
* Participant has had a thyroidectomy, or thyroid disease requiring medication during the last 12 months

Primary outcomes:
measure: Number of Participants With Local and Systemic Reactogenicity Events Over 8 Days After First Vaccination
timeFrame: Day 8
measure: Number of Participants With Local and Systemic Reactogenicity Events Over 8 Days After Second Vaccination
timeFrame: Day 36
measure: Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs)
timeFrame: Week 52 or early withdrawal
Secondary outcomes:
measure: Envelop (Env) Binding Antibody Titer at Week 8
timeFrame: Week 8
Other outcomes:
Locations:
city: Miami
country: United States
state: Florida
Study officials:
affiliation: Crucell Holland BV
name: Crucell Holland BV Clinical Trials
role: STUDY_DIRECTOR
References: