Malaria
Conditions
Brief summary
This study is a Phase 1, dose escalation, first-in-human study designed primarily to evaluate the safety of the purified plant-derived Pfs25 VLP combined with Alhydrogel adjuvant
Interventions
BIOLOGICALPfs25 VLP- FhCMB
Sponsors
Fraunhofer, Center for Molecular Biotechnology
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* Male or non-pregnant, non-lactating female aged 18 - 50 years inclusive * Able to give written informed consent obtained prior to screening * Healthy, as determined by medical history, physical examination, vital signs, and clinical safety laboratory examinations at baseline * Women of childbearing potential must have a negative urine pregnancy test within 24 hours preceding receipt of each dose. * Females should fulfill one of the following criteria: 1. At least one year post-menopausal 2. Surgically sterile 3. Willing to use oral, implantable, transdermal or injectable contraceptives for 30 days prior to first vaccination and then for the study duration 4. Willing to abstain from sexual intercourse or use another reliable form of contraception approved by the Investigator (e.g., intrauterine device (IUD), female condom, diaphragm with spermicide, cervical cap, use of condom by the sexual partner or a sterile sexual partner) for 30 days prior to first vaccination through 9 months after third vaccination * Comprehension of the study requirements, as demonstrated by achieving a score of at least 80% correct on a short multiple-choice quiz. * Individuals who fail to achieve a passing score on the initial comprehension assessment will be given the opportunity to retest after a review of protocol information. * Individuals who fail the comprehension assessment for the second time will not be enrolled. * Available and able to participate in all planned study visits and procedures.
Exclusion criteria
* History of malaria or previous receipt of an investigational malaria vaccine
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Subjects With at Least One Adverse Event | 336 days |
| Subjects With Solicited Systemic Adverse Events | 336 days |
| Subjects With Solicited Local Adverse Events | 336 days |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Assessment of Anti-Pfs25 IgG Following the Third Immunization. | 196 days | Serum anti-Pfs25 antibody IgG titers determined using an ELISA unit assay. |
| Assessment of Transmission Reducing Activity (TRA) of Malaria Parasite | 84 days | Assessment of TRA, as measured by the standard membrane feeding assay (SMFA), one month after the second vaccination (Study Day 84) in either the 30 μg or 100 μg dose groups. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 2 µg + Alhydrogel Pfs25 VLP- FhCMB vaccine | 6 |
| 10 µg + Alhydrogel Pfs25 VLP- FhCMB vaccine | 6 |
| 30 µg + Alhydrogel Pfs25 VLP- FhCMB vaccine | 16 |
| 100 µg + Alhydrogel Pfs25 VLP- FhCMB vaccine | 16 |
| Total | 44 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 0 | 1 | 0 |
| Overall Study | Missed visits due to patient travel | 0 | 0 | 1 | 0 |
| Overall Study | Protocol Violation | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | 2 µg + Alhydrogel | 10 µg + Alhydrogel | 30 µg + Alhydrogel | 100 µg + Alhydrogel | Total |
|---|---|---|---|---|---|
| Age, Customized | 36.8 years STANDARD_DEVIATION 8.93 | 36.7 years STANDARD_DEVIATION 6.59 | 36.1 years STANDARD_DEVIATION 8.96 | 30.6 years STANDARD_DEVIATION 8.86 | 34.3 years STANDARD_DEVIATION 8.82 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 1 Participants | 1 Participants | 1 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 5 Participants | 15 Participants | 14 Participants | 38 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 3 Participants | 10 Participants | 11 Participants | 28 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 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 2 Participants | 6 Participants | 5 Participants | 15 Participants |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 7 Participants | 5 Participants | 18 Participants |
| Sex: Female, Male Male | 3 Participants | 3 Participants | 9 Participants | 11 Participants | 26 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 | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 6 | 4 / 6 | 8 / 16 | 10 / 16 |
| serious Total, serious adverse events | 0 / 6 | 1 / 6 | 0 / 16 | 1 / 16 |
Outcome results
Primary
Subjects With at Least One Adverse Event
Time frame: 336 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 2 µg + Alhydrogel | Subjects With at Least One Adverse Event | 4 Participants |
| 10 µg + Alhydrogel | Subjects With at Least One Adverse Event | 4 Participants |
| 30 µg + Alhydrogel | Subjects With at Least One Adverse Event | 11 Participants |
| 100 µg + Alhydrogel | Subjects With at Least One Adverse Event | 15 Participants |
Primary
Subjects With Solicited Local Adverse Events
Time frame: 336 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 2 µg + Alhydrogel | Subjects With Solicited Local Adverse Events | 4 Participants |
| 10 µg + Alhydrogel | Subjects With Solicited Local Adverse Events | 6 Participants |
| 30 µg + Alhydrogel | Subjects With Solicited Local Adverse Events | 12 Participants |
| 100 µg + Alhydrogel | Subjects With Solicited Local Adverse Events | 15 Participants |
Primary
Subjects With Solicited Systemic Adverse Events
Time frame: 336 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 2 µg + Alhydrogel | Subjects With Solicited Systemic Adverse Events | 2 Participants |
| 10 µg + Alhydrogel | Subjects With Solicited Systemic Adverse Events | 4 Participants |
| 30 µg + Alhydrogel | Subjects With Solicited Systemic Adverse Events | 8 Participants |
| 100 µg + Alhydrogel | Subjects With Solicited Systemic Adverse Events | 10 Participants |
Secondary
Assessment of Anti-Pfs25 IgG Following the Third Immunization.
Serum anti-Pfs25 antibody IgG titers determined using an ELISA unit assay.
Time frame: 196 days
Population: In the 30 µg + Alhydrogel group, 15 out of 16 patient samples were analyzed as 1 patient in the group had withdrawn from the study by study day 196. In the 100 µg + Alhydrogel group, 13 out of 16 patient samples were analyzed due to 2 patients in the group withdrawing from the study and an insufficient serum sample from a third patient.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| 2 µg + Alhydrogel | Assessment of Anti-Pfs25 IgG Following the Third Immunization. | 139.2 Antibody Titer |
| 10 µg + Alhydrogel | Assessment of Anti-Pfs25 IgG Following the Third Immunization. | 511.2 Antibody Titer |
| 30 µg + Alhydrogel | Assessment of Anti-Pfs25 IgG Following the Third Immunization. | 492.9 Antibody Titer |
| 100 µg + Alhydrogel | Assessment of Anti-Pfs25 IgG Following the Third Immunization. | 996.0 Antibody Titer |
p-value: <0.001Wilcoxon (Mann-Whitney)
p-value: <0.001Wilcoxon (Mann-Whitney)
Secondary
Assessment of Transmission Reducing Activity (TRA) of Malaria Parasite
Assessment of TRA, as measured by the standard membrane feeding assay (SMFA), one month after the second vaccination (Study Day 84) in either the 30 μg or 100 μg dose groups.
Time frame: 84 days
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 30 µg + Alhydrogel | Assessment of Transmission Reducing Activity (TRA) of Malaria Parasite | 3.5 % TRA |
| 100 µg + Alhydrogel | Assessment of Transmission Reducing Activity (TRA) of Malaria Parasite | 4.3 % TRA |
p-value: 0.8Wilcoxon (Mann-Whitney)
p-value: 0.6Wilcoxon (Mann-Whitney)
Secondary
Assessment of Transmission Reducing Activity (TRA) of Malaria Parasite
Assessment of TRA, as measured by the standard membrane feeding assay (SMFA), showing ≥80% reduction of oocysts in Anopheles mosquito gut in ≥50% of the subjects with Study Day 196 sera (one month after the third vaccination) (Study Day 196) in either the 30 μg or 100 μg dose groups.
Time frame: 196 days
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 30 µg + Alhydrogel | Assessment of Transmission Reducing Activity (TRA) of Malaria Parasite | 9.1 % TRA |
| 100 µg + Alhydrogel | Assessment of Transmission Reducing Activity (TRA) of Malaria Parasite | 22.5 % TRA |
p-value: 0.5Wilcoxon (Mann-Whitney)
p-value: 0.3Wilcoxon (Mann-Whitney)