HIV Infection
Conditions
Keywords
vaccine, healthy volunteer
Brief summary
This study is designed to evaluate the safety of the FLSC vaccine and will be a randomized, placebo-controlled, modified double-blinded dose escalation study in 60 healthy adult volunteers (Human Immunodeficiency Virus-1 uninfected).
Detailed description
This is a Phase 1 randomized, placebo-controlled, modified double-blinded dose escalation study in 60 healthy adult volunteers who are Human Immunodeficiency Virus-1 (HIV-1) uninfected. Participants in the study will receive 4 injections at 0, 4, 8 and 24 weeks and will be followed for an additional 24 weeks. The total study duration will be 48 weeks. As this is a Phase 1 trial, the primary objective is to document safety of the Full Length Single Chain (FLSC) gp120-CD4 complex vaccine with a secondary objective to evaluate immune responses induced by the vaccine. This vaccine is being evaluated as it is constructed so that the gp120 and CD4 moieties form a stable intra-chain binding interaction that forms a transition state structure that presents conserved, conformational domains involved in the early HIV replication process. It is hypothesized that antibodies directed to these epitopes would be highly cross-reactive and potentially useful for HIV vaccine development.
Interventions
BIOLOGICAL300 ug FLSC vaccine
FLSC vaccine 300 ug (1.0 mL) given by intramuscular injection into the arm on study Days 0, 28, 56, 168
BIOLOGICAL150 ug FLSC vaccine
FLSC vaccine 150 ug (0.5 mL) given by intramuscular injection into the arm on study Days 0, 28, 56, 168
BIOLOGICAL75 ug FLSC vaccine
FLSC vaccine 75 ug (0.25 mL) given by intramuscular injection into the arm on study Days 0, 28, 56, 168
BIOLOGICALPlacebo
Placebo sterile saline (0.25 - 1.0 mL) given by intramuscular injection into the arm on study Days 0, 28, 56, 168
Sponsors
Bill and Melinda Gates Foundation
Auro Vaccines LLC
University of Maryland, Baltimore
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
1. Age: 18 to 45 years of age. 2. Sex: Male or Female (female volunteers of child bearing potential must have a negative serum beta human chorionic gonadotropin (b-HCG or pregnancy) test at time of screening and entry into the study and provide assurance of the use of effective(as judged by the investigator) birth control methods or abstinence beginning at least 60 days prior to the study and during the study 3. Documented HIV-1 negative by ELISA 4. Be in good general health without clinically significant medical history, physical examination findings, or clinically significant abnormal laboratory results (i.e., chronic medical conditions as noted in the
Exclusion criteria
such as cancer as well as any conditions that in the opinion of the investigator might pose a risk to the volunteer) 5. No identifiable risk factor for acquisition of HIV infection (i.e., intravenous drug use/needle sharing, unprotected sex with multiple partners) 6. Negative b-HCG pregnancy test on the day of initial vaccination. 7. Negative screen for Hepatitis B surface antigen (HBsAg); 8. Negative screen for antibodies to Hepatitis C virus (Patient may enroll if patient can provide documentation of negative hepatitis C viral load.) 9. Participant must have a CD4 count ( a type of white blood cells) within the normal range of the clinical laboratory utilized for the study and a CD4 percentage within 20% of the normal range of the clinical laboratory 10. Laboratory parameters must be within pre-specified limits as defined by
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Local and Systemic Reactogenicity Signs and Symptoms | 48 weeks | Signs and symptoms include pain, tenderness, maximum severity of pain and/or tenderness, erythema, induration, fever, malaise/fatigue, myalgia, headache, nausea, vomiting, chills, arthralgia, and maximum severity of systemic symptoms. |
| Number of Participants With Related Adverse Events | 48 weeks | Treatment emergent adverse events assessed by investigator to be either possibly, probably, or definitely related to study treatment. Medical Dictionary for Regulatory Activities (MedDRA) preferred term, severity, and assessed relationship to study products. |
| Number of Participants With Sustained Decrease in CD4 Count and CD4%. | 48 weeks | CD4 count was monitored from baseline and at each study visit through study completion. Baseline CD4 and CD4% levels were calculated by taking the average of the screening and first vaccination visits. The number of individuals who had sustained (2 consecutive time points) 30% decrease in CD4 cell/ul and CD4% from baseline were counted. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Binding Antibody Response Rates to FLSC | 2 weeks after 4th (last) vaccination. | Percent of participants with anti-FLSC antibodies as assessed by ELISA by 2 weeks after final vaccination |
| Binding Antibody Response Rates to BaL-gp120 | 2 weeks after 4th (last) vaccination | Percent of participants with anti-gp120 antibodies as assessed by ELISA |
| Competitive Antibody Rates to CD4i Epitopes | 2 weeks after 4th (last) vaccination | Percent of participants with antibodies competing with A32 or 17b as assessed by ELISA. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 300 ug FLSC Vaccine Highest dose vaccine group | 18 |
| 150 ug FLSC Vaccine Middle dose vaccine group | 16 |
| 75 ug FLSC Vaccine Lowest dose vaccine group | 15 |
| Placebo Placebo control group | 16 |
| Total | 65 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 3 | 1 | 1 | 1 |
| Overall Study | Physician Decision | 1 | 0 | 0 | 0 |
| Overall Study | Protocol Violation | 0 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 1 | 3 |
Baseline characteristics
| Characteristic | 300 ug FLSC Vaccine | 150 ug FLSC Vaccine | 75 ug FLSC Vaccine | Placebo | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 18 Participants | 16 Participants | 15 Participants | 16 Participants | 65 Participants |
| Age, Continuous | 32.1 years STANDARD_DEVIATION 8.8 | 33.3 years STANDARD_DEVIATION 7.2 | 36.5 years STANDARD_DEVIATION 5.5 | 32.2 years STANDARD_DEVIATION 7.5 | 33.4 years STANDARD_DEVIATION 7.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants | 2 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 17 Participants | 16 Participants | 14 Participants | 14 Participants | 61 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 13 Participants | 8 Participants | 11 Participants | 11 Participants | 43 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) White | 1 Participants | 7 Participants | 4 Participants | 4 Participants | 16 Participants |
| Region of Enrollment United States | 18 participants | 16 participants | 15 participants | 16 participants | 65 participants |
| Sex: Female, Male Female | 6 Participants | 6 Participants | 7 Participants | 8 Participants | 27 Participants |
| Sex: Female, Male Male | 12 Participants | 10 Participants | 8 Participants | 8 Participants | 38 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 18 | 0 / 16 | 0 / 15 | 0 / 16 |
| other Total, other adverse events | 17 / 18 | 16 / 16 | 14 / 15 | 12 / 16 |
| serious Total, serious adverse events | 0 / 18 | 2 / 16 | 2 / 15 | 0 / 16 |
Outcome results
Primary
Number of Participants With Local and Systemic Reactogenicity Signs and Symptoms
Signs and symptoms include pain, tenderness, maximum severity of pain and/or tenderness, erythema, induration, fever, malaise/fatigue, myalgia, headache, nausea, vomiting, chills, arthralgia, and maximum severity of systemic symptoms.
Time frame: 48 weeks
Population: Intention-to-treat Population - All subjects who received at least one dose of vaccine/placebo
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 300 ug FLSC Vaccine | Number of Participants With Local and Systemic Reactogenicity Signs and Symptoms | Diarrhea | 0 Participants |
| 300 ug FLSC Vaccine | Number of Participants With Local and Systemic Reactogenicity Signs and Symptoms | Pyrexia | 1 Participants |
| 300 ug FLSC Vaccine | Number of Participants With Local and Systemic Reactogenicity Signs and Symptoms | Dizziness | 0 Participants |
| 300 ug FLSC Vaccine | Number of Participants With Local and Systemic Reactogenicity Signs and Symptoms | Nausea | 0 Participants |
| 300 ug FLSC Vaccine | Number of Participants With Local and Systemic Reactogenicity Signs and Symptoms | Pruritus | 1 Participants |
| 300 ug FLSC Vaccine | Number of Participants With Local and Systemic Reactogenicity Signs and Symptoms | Headache | 0 Participants |
| 300 ug FLSC Vaccine | Number of Participants With Local and Systemic Reactogenicity Signs and Symptoms | Chills | 0 Participants |
| 300 ug FLSC Vaccine | Number of Participants With Local and Systemic Reactogenicity Signs and Symptoms | Fatigue | 0 Participants |
| 300 ug FLSC Vaccine | Number of Participants With Local and Systemic Reactogenicity Signs and Symptoms | Injection site pain | 3 Participants |
| 150 ug FLSC Vaccine | Number of Participants With Local and Systemic Reactogenicity Signs and Symptoms | Fatigue | 2 Participants |
| 150 ug FLSC Vaccine | Number of Participants With Local and Systemic Reactogenicity Signs and Symptoms | Diarrhea | 1 Participants |
| 150 ug FLSC Vaccine | Number of Participants With Local and Systemic Reactogenicity Signs and Symptoms | Pyrexia | 1 Participants |
| 150 ug FLSC Vaccine | Number of Participants With Local and Systemic Reactogenicity Signs and Symptoms | Headache | 3 Participants |
| 150 ug FLSC Vaccine | Number of Participants With Local and Systemic Reactogenicity Signs and Symptoms | Injection site pain | 8 Participants |
| 150 ug FLSC Vaccine | Number of Participants With Local and Systemic Reactogenicity Signs and Symptoms | Pruritus | 1 Participants |
| 150 ug FLSC Vaccine | Number of Participants With Local and Systemic Reactogenicity Signs and Symptoms | Dizziness | 0 Participants |
| 150 ug FLSC Vaccine | Number of Participants With Local and Systemic Reactogenicity Signs and Symptoms | Chills | 0 Participants |
| 150 ug FLSC Vaccine | Number of Participants With Local and Systemic Reactogenicity Signs and Symptoms | Nausea | 0 Participants |
| 75 ug FLSC Vaccine | Number of Participants With Local and Systemic Reactogenicity Signs and Symptoms | Fatigue | 0 Participants |
| 75 ug FLSC Vaccine | Number of Participants With Local and Systemic Reactogenicity Signs and Symptoms | Injection site pain | 4 Participants |
| 75 ug FLSC Vaccine | Number of Participants With Local and Systemic Reactogenicity Signs and Symptoms | Headache | 1 Participants |
| 75 ug FLSC Vaccine | Number of Participants With Local and Systemic Reactogenicity Signs and Symptoms | Pruritus | 1 Participants |
| 75 ug FLSC Vaccine | Number of Participants With Local and Systemic Reactogenicity Signs and Symptoms | Nausea | 2 Participants |
| 75 ug FLSC Vaccine | Number of Participants With Local and Systemic Reactogenicity Signs and Symptoms | Pyrexia | 0 Participants |
| 75 ug FLSC Vaccine | Number of Participants With Local and Systemic Reactogenicity Signs and Symptoms | Diarrhea | 0 Participants |
| 75 ug FLSC Vaccine | Number of Participants With Local and Systemic Reactogenicity Signs and Symptoms | Chills | 2 Participants |
| 75 ug FLSC Vaccine | Number of Participants With Local and Systemic Reactogenicity Signs and Symptoms | Dizziness | 1 Participants |
| Placebo | Number of Participants With Local and Systemic Reactogenicity Signs and Symptoms | Diarrhea | 1 Participants |
| Placebo | Number of Participants With Local and Systemic Reactogenicity Signs and Symptoms | Nausea | 1 Participants |
| Placebo | Number of Participants With Local and Systemic Reactogenicity Signs and Symptoms | Pruritus | 2 Participants |
| Placebo | Number of Participants With Local and Systemic Reactogenicity Signs and Symptoms | Dizziness | 0 Participants |
| Placebo | Number of Participants With Local and Systemic Reactogenicity Signs and Symptoms | Chills | 0 Participants |
| Placebo | Number of Participants With Local and Systemic Reactogenicity Signs and Symptoms | Headache | 2 Participants |
| Placebo | Number of Participants With Local and Systemic Reactogenicity Signs and Symptoms | Pyrexia | 1 Participants |
| Placebo | Number of Participants With Local and Systemic Reactogenicity Signs and Symptoms | Fatigue | 1 Participants |
| Placebo | Number of Participants With Local and Systemic Reactogenicity Signs and Symptoms | Injection site pain | 5 Participants |
Primary
Number of Participants With Related Adverse Events
Treatment emergent adverse events assessed by investigator to be either possibly, probably, or definitely related to study treatment. Medical Dictionary for Regulatory Activities (MedDRA) preferred term, severity, and assessed relationship to study products.
Time frame: 48 weeks
Population: Intention-to-treat population: Subjects who have received at least one dose of vaccine/placebo.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 300 ug FLSC Vaccine | Number of Participants With Related Adverse Events | 7 Participants |
| 150 ug FLSC Vaccine | Number of Participants With Related Adverse Events | 9 Participants |
| 75 ug FLSC Vaccine | Number of Participants With Related Adverse Events | 7 Participants |
| Placebo | Number of Participants With Related Adverse Events | 8 Participants |
Primary
Number of Participants With Sustained Decrease in CD4 Count and CD4%.
CD4 count was monitored from baseline and at each study visit through study completion. Baseline CD4 and CD4% levels were calculated by taking the average of the screening and first vaccination visits. The number of individuals who had sustained (2 consecutive time points) 30% decrease in CD4 cell/ul and CD4% from baseline were counted.
Time frame: 48 weeks
Population: The analysis included number of participants with sustained (2 consecutive time points) of 30% decrease in CD4 cell/ul and CD4%.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 300 ug FLSC Vaccine | Number of Participants With Sustained Decrease in CD4 Count and CD4%. | 0 Participants |
| 150 ug FLSC Vaccine | Number of Participants With Sustained Decrease in CD4 Count and CD4%. | 0 Participants |
| 75 ug FLSC Vaccine | Number of Participants With Sustained Decrease in CD4 Count and CD4%. | 0 Participants |
| Placebo | Number of Participants With Sustained Decrease in CD4 Count and CD4%. | 0 Participants |
Secondary
Binding Antibody Response Rates to BaL-gp120
Percent of participants with anti-gp120 antibodies as assessed by ELISA
Time frame: 2 weeks after 4th (last) vaccination
Population: Sample size in each group was less than safety time point because of 8 volunteers who were lost to follow-up, 5 missed vaccination visits/samples, and several samples that had high background levels to individual assays.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 300 ug FLSC Vaccine | Binding Antibody Response Rates to BaL-gp120 | 30 percentage of participants |
| 150 ug FLSC Vaccine | Binding Antibody Response Rates to BaL-gp120 | 46 percentage of participants |
| 75 ug FLSC Vaccine | Binding Antibody Response Rates to BaL-gp120 | 9 percentage of participants |
| Placebo | Binding Antibody Response Rates to BaL-gp120 | 0 percentage of participants |
Secondary
Binding Antibody Response Rates to FLSC
Percent of participants with anti-FLSC antibodies as assessed by ELISA by 2 weeks after final vaccination
Time frame: 2 weeks after 4th (last) vaccination.
Population: Sample size in each group was less than safety time point because of 8 volunteers who were lost to follow-up, 5 missed vaccination visits/samples, and several samples that had high background levels to individual assays.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 300 ug FLSC Vaccine | Binding Antibody Response Rates to FLSC | 100 percentage of participants |
| 150 ug FLSC Vaccine | Binding Antibody Response Rates to FLSC | 100 percentage of participants |
| 75 ug FLSC Vaccine | Binding Antibody Response Rates to FLSC | 100 percentage of participants |
| Placebo | Binding Antibody Response Rates to FLSC | 0 percentage of participants |
Secondary
Competitive Antibody Rates to CD4i Epitopes
Percent of participants with antibodies competing with A32 or 17b as assessed by ELISA.
Time frame: 2 weeks after 4th (last) vaccination
Population: Sample size in each group was less than safety time point because of 8 volunteers who were lost to follow-up, 5 missed vaccination visits/samples, and several samples that had high background levels to individual assays.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 300 ug FLSC Vaccine | Competitive Antibody Rates to CD4i Epitopes | 100 percentage of participants |
| 150 ug FLSC Vaccine | Competitive Antibody Rates to CD4i Epitopes | 100 percentage of participants |
| 75 ug FLSC Vaccine | Competitive Antibody Rates to CD4i Epitopes | 64 percentage of participants |
| Placebo | Competitive Antibody Rates to CD4i Epitopes | 0 percentage of participants |