Clinical trial NCT03547245: A Phase I Trial to Evaluate the Safety and Immunogenicity of eOD-GT8 60mer Vaccine, Adjuvanted
Official title: A Phase 1, Randomized, Double-blind, Placebo-controlled Dosage Escalation Trial to Evaluate the Safety and Immunogenicity of eOD-GT8 60mer Vaccine, Adjuvanted in HIV-uninfected, Healthy Adult Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV/AIDS
Lead sponsor: International AIDS Vaccine Initiative
Sponsor class: NETWORK
First posted: 2018-06-06
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: PREVENTION

Brief summary: This is a phase 1 first-in-human clinical trial to assess the safety, tolerability, and immunogenicity of eOD-GT8 60mer Vaccine, Adjuvanted, in up to 48 healthy adult HIV-negative volunteers.

Detailed description: This is a phase 1 first-in-human clinical trial to assess the safety, tolerability, and immunogenicity of eOD-GT8 60mer Vaccine, Adjuvanted, in up to 48 healthy adult HIV-negative volunteers. The study is a randomized, double-blind, placebo-controlled dosage-escalation Phase 1 study intended to evaluate the safety and immunogenicity of eOD-GT8 60mer Vaccine, Adjuvanted in a prime-boost regimen.

Eligibility criteria: Inclusion Criteria:

1. Healthy male and female, including transgender individuals, as assessed by a medical history, physical exam, and laboratory tests;
2. At least 18 years of age on the day of screening and has not reached his/her 51st birthday on the day of first IP administration;
3. Willing to comply with the requirements of the protocol and available for follow-up for the planned duration of the study;
4. In the opinion of the Principal Investigator or designee and based on Assessment of Informed Consent Understanding results, has understood the information provided and potential impact and/or risks linked to vaccination and participation in the trial; written informed consent will be obtained from the volunteer before any study-related procedures are performed;
5. Willing to undergo HIV testing, risk reduction counseling and receive HIV test result;
6. All heterosexually active female volunteers must commit to use an effective method of contraception for 4 months following investigational product administration
7. All female volunteers must be willing to undergo urine pregnancy tests at time points indicated in the Schedule of Procedures and must test negative prior to each study vaccination;
8. All sexually active males (unless anatomically sterile or in a monogamous relationship with a female partner who uses a documented non-barrier method of birth control) must be willing to use an effective method of contraception (such as consistent condom use) from the day of first vaccination until at least 4 months after the last vaccination ;
9. Willing to forgo donations of blood, or any other tissues during the study and, for those who test HIV-positive due to vaccine-induced antibodies, until the anti-HIV antibody titers become undetectable;
10. Women, who are not heterosexually active at screening, must agree to utilize an effective method of contraception if they become hetero-sexually active, as outlined above.

Exclusion Criteria:

1. Confirmed HIV-1 or HIV-2 infection; any clinically relevant abnormality on history or examination including history of immunodeficiency or autoimmune disease; use of systemic corticosteroids (the use of topical, nasal or inhaled steroids is permitted), immunosuppressive, anticancer, anti-tuberculosis or other medications considered significant by the investigator within the previous 6 months;
2. The following exceptions are permitted and will not exclude study participation: use of corticosteroid nasal spray for rhinitis, topical corticosteroids for an acute uncomplicated dermatitis; or a short course (duration of 10 days or less, or a single injection) of corticosteroid for a non-chronic condition (based on investigator clinical judgment) at least 2 weeks prior to enrollment in this study;
3. Any clinically significant acute or chronic medical condition that is considered progressive or in the opinion of the investigator makes the volunteer unsuitable for participation in the study;
4. Reported risky behavior for HIV infection within 12 months prior to vaccination
5. If female, pregnant or planning a pregnancy during the period of enrollment until 4 months after the last study vaccination; or lactating;
6. Bleeding disorder that was diagnosed by a physician (e.g., clotting factor deficiency, coagulopathy or platelet disorder that requires special precautions) (Note: A volunteer who states that he or she has easy bruising or bleeding, but does not have a formal diagnosis and has had IM vaccine administrations and blood draws without any adverse experience, is eligible);
7. Infectious disease: chronic hepatitis B infection (HbsAg-positive), current hepatitis C infection (HCV Ab positive and HCV RNA positive) treatment for chronic hepatitis C infection in the past year, or active syphilis (positive RPR confirmed by TPHA);
8. Receipt of live attenuated vaccine within the previous 30 days or planned receipt within 30 days after vaccination with Investigational Product; or receipt of other vaccine within the previous 14 days or planned receipt within 14 days after vaccination with Investigational Product. (Exception is live attenuated influenza vaccine within 14 days);
9. History of splenectomy;
10. Receipt of blood transfusion or blood-derived products within the previous 3 months;
11. Any of the following abnormal laboratory parameters listed below:

    Hematology
    * Hematocrit: \<35%
    * Absolute Neutrophil Count (ANC): ≤1,000/mm3
    * Absolute Lymphocyte Count (ALC): ≤650/mm3
    * Platelets: \<125,000 cells/mm3 Chemistry
    * Creatinine \>1.1 x upper limit of normal (ULN)
    * ALT \>1.25 x ULN
    * AST \>1.25 x ULN Urinalysis
    * Clinically significant abnormal dipstick confirmed by microscopy:
    * Protein = 1+ or more
    * Blood = 2+ or more (not due to menses)
12. Participation in another clinical trial of an Investigational Product currently, within the previous 3 months or expected participation during this study (Concurrent participation in an observational trial not requiring any blood or tissue sample collection is not an exclusion);
13. Prior receipt of another investigational HIV vaccine candidate (Note: receipt of placebo in a previous HIV vaccine trial will not exclude a volunteer from participation if documentation is available and the Medical Monitor gives approval);
14. History of severe local or systemic reactogenicity to vaccines (e.g., anaphylaxis, respiratory difficulties, angioedema, injection site necrosis or ulceration);
15. Psychiatric condition that compromises safety of the volunteer and precludes compliance with the protocol. Specifically excluded are persons with psychoses within the past 3 years (prior to screening), ongoing risk for suicide, or history of suicide attempt or gesture within the past 3 years;
16. Seizure disorder: A volunteer who has had a seizure in the last 3 years (prior to screening) is excluded. (Not excluded: a volunteer with a history of seizures who has neither required medications nor had a seizure for 3 years);
17. A history of malignancy in the past 5 years (prior to screening) or ongoing malignancy (A history of a completely excised malignancy that is considered cured is not an exclusion);
18. Active, serious infections requiring parenteral antibiotic, antiviral or antifungal therapy within 30 days prior to enrollment;
19. Body mass index ≥35 ;
20. Body weight \<110 pounds (55 kg);
21. If, in the opinion of the Principal Investigator, it is not in the best interest of the volunteer to participate in the trial.

Primary outcomes:
measure: Safety and Tolerability: frequency of local and systemic reactogenicity events
timeFrame: 7 days
measure: Safety and Tolerability: proportion of volunteers with moderate or greater unsolicited adverse events
timeFrame: 16 months
measure: Safety and Tolerability: proportion of volunteers in each group with potential immune-mediated diseases (pIMDs)
timeFrame: 16 months
Secondary outcomes:
measure: Immunogenicity: Frequency of responses
timeFrame: 16 months
measure: Immunogenicity: Magnitude of responses
timeFrame: 16 months
Other outcomes:
Locations:
city: Washington
country: United States
facility: George Washington University
state: District of Columbia
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
Study officials:
affiliation: George Washington University School of Medicine & Health Sciences
name: David Diemert, MD, FRCP(C)
role: PRINCIPAL_INVESTIGATOR
affiliation: Seattle HIV Vaccine Trials Unit
name: Julie McElrath, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: