Overview

A Trial For The Study of Falciparum Malaria Protein 013 Administered Via Intramuscular Injection in Healthy Adults

Status:
Recruiting
Trial end date:
2022-12-01
Target enrollment:
0
Participant gender:
All
Summary
A Phase 1, open label clinical study to evaluate the safety, immunogenicity, tolerability and efficacy of Plasmodium falciparum Malaria Protein 013 (FMP013) combined with (ALF with QS-21), saponin molecule derived from the bark of Quillaja species (ALFQ)) in healthy adult volunteers at different doses and dosing schedules.
Phase:
Phase 1
Accepts Healthy Volunteers?
Accepts Healthy Volunteers
Details
Lead Sponsor:
U.S. Army Medical Research and Development Command
Collaborator:
Walter Reed Army Institute of Research (WRAIR)
Criteria
Inclusion Criteria:

1. Healthy adults between the ages 18-55 (inclusive);

2. Able and willing to provide written, informed consent;

3. Able and willing to comply with all research requirements, in the opinion of the
Investigator;

4. Agreement to refrain from blood donation during the course of the study. Volunteers
who have undergone CHMI can donate to other research once the study is complete but
cannot donate to the American Red Cross for at least 3 years after the CHMI event;

5. Laboratory Criteria within 90 days before enrollment:

- Hemoglobin ≥ 11.7 g/dL for women; ≥ 12.0 g/dL for men;

- White Blood Cell count = 3,800-10,800 cells/mm3;

- Platelets = 140,000-400,000/mm3;

- Alanine aminotransferase (ALT; SGPT) 9-46 U/L male and 6-29 U/L female;

- Serum creatinine ≤ 1.5 mg/dL;

- Negative HIV testing (HIV Ab / antigen 4th generation screen with reflex
confirmatory RNA testing);

- Negative hepatitis B surface antigen (HBsAg) and hepatitis C antibody testing;
Note: As above, Grade 1 lab abnormalities detected on screening may be repeated
at PI discretion. Persistent Grade 1 abnormalities that are felt to represent the
non-pathologic baseline for the subject will be discussed with the research
monitor and documented before a subject is enrolled in the trial, and are
allowable per discretion and agreement of the PI and Research Monitor

6. Birth control requirements:

Female subjects must meet one of the following 2 criteria:

- No reproductive potential due to post-menopausal status (12 months of natural
[spontaneous] amenorrhea) or hysterectomy, bilateral oophorectomy or tubal
ligation;

- Women of childbearing potential should agree to practice highly effective
contraception at least 30 days before enrollment and through 3 months post-CHMI
or post-last vaccination (whichever is latest), using one of the following
methods: condoms (male or female) with spermicide; diaphragm, or cervical cap
with spermicide; intrauterine device; contraceptive pills, patch, injection,
intravaginal ring or other FDA-approved contraceptive method; male partner has
previously undergone a vasectomy; abstinence.

Male subjects are encouraged but not required to practice highly effective
contraception to avoid pregnancy in their partner from 30 days prior to enrollment
through 60 days post-CHMI. This is due to the potential impact of malaria and
antimalarial medications on spermatogenesis.

7. For all female subjects except those with a history of hysterectomy or bilateral
oophorectomy, a negative β-HCG pregnancy test (urine) on day of enrollment, each day
of vaccination, and the day of CHMI (tubal ligations have a not insignificant failure
rate, 12 months of spontaneous amenorrhea does not completely preclude pregnancy and
can be a result of polycystic ovarian syndrome);

8. Reachable (24/7) by mobile phone or other method of communication (email, landline,
etc) during the period between CHMI and 28 days post-CHMI, per volunteer report;

9. No plans to travel outside the Washington DC metro area (DC, Maryland, and Virginia)
between the day of challenge and 28 days post-challenge; For Travel outside the US
occurring 28 days post-challenge to a malaria endemic area inclusion will be at the
discretion of the PI.

10. If a subject is active duty military, he or she must obtain approval from his or her
supervisor per WRAIR Policy 11-45;

11. Must have low (< 10%) cardiac risk factors according to clinical Gaziano (NHANES I)
criteria assessed at screening, and a normal or normal variant ECG;

12. Completion of Study Comprehension Quiz (minimum passing score of 80% with 2 attempts
permitted).

13. Subject must be willing to take anti-malarial treatment after CHMI;

14. Subject must provide 2 emergency contacts who will be made aware of the subject's
participation in this trial and the vital importance of being reached during the
challenge phase of the study. Both contacts must be verified by pone prior to subject
enrollment.

Verification will be define as either speaking to the emergency contact over the phone,
hearing their name included in the voicemail response, or confirming the emergency contact
uses the number if a third party answers the phone.

Exclusion Criteria:

1. History of malaria infection (any species) or residence in a malaria-endemic area for
more than 5 years (includes previous participation in CHMI studies).

2. Previous travel to malaria endemic regions within the past 6 months before study
enrollment defined as first vaccination or day of challenge (for infectivity controls)
or planned travel to malaria endemic regions during the vaccination, CHMI and 28-day
CHMI follow-up period; For Travel outside the US occurring 28 days post-challenge to a
malaria endemic area exclusion will be at the discretion of the PI.

3. Any history of receiving a malaria vaccine.

4. Received an investigational product in the 30 days before enrollment, or planned to
receive during the study period.

5. Concurrent participation in another clinical research study.

6. Any use of medications that prevent or treat malaria during the 1 month prior to
challenge or planned use during the study (outside of the drugs provided by the study
team).

7. Any serious medical illness or condition involving the heart, liver, lungs, or
kidneys.

8. Any significant risk for developing heart disease in the next 5 years, assessed
according to clinical Gaziano (NHANES I) criteria assessed at screening, and an ECG.

9. Receipt of immunoglobulins or blood products within 3 months before enrollment.

10. Any history of anaphylaxis.

11. History of sickle cell trait or disease, or any condition that could affect
susceptibility to malaria infection, per subject verbal report.

12. Pregnancy, lactation, or intention to become pregnant during the study, and 3 months
after malaria challenge, if applicable.

13. Contraindications or allergies to the use of all 3 proposed anti-malarial medications;
Malarone (atovaquone/proguanil), Coartem (artemether/lumefantrine) and chloroquine;
contraindication to 1 or 2 is not exclusionary.

14. History of active/recent cancer still within treatment or active surveillance
follow-up (except basal cell carcinoma of the skin and cervical carcinoma in situ).
Treated/resolved cancers with no likelihood of recurrence may be deemed acceptable at
Principal investigator discretion

15. History of autoimmune disease.

16. Significant (eg systemic anaphylaxis) hypersensitivity reactions to mosquito bites
(local reactions at the site of mosquito bites are not an exclusion criterion)
requiring hospitalization.

17. Suspected or known current alcohol or drug abuse as defined by an alcohol intake of
greater than 3 drinks a day on average for a man, and greater than 2 drinks a day on
average for a woman.

18. Any other significant disease, disorder or finding which may significantly increase
the risk to the volunteer because of participation in the study, affect the ability of
the volunteer to give informed consent, participate in the study, or impair
interpretation of the study data, in the opinion of the Investigator.

19. Current anti-tuberculosis prophylaxis or treatment.

20. History of splenectomy.

21. History of confirmed or suspected immunodeficiency.

22. History of Hereditary angioedema (HAE), acquired angioedema (AAE), or idiopathic forms
of angioedema.

23. History of Asthma that is unstable or required emergent care, urgent care,
hospitalization or intubation during the past 2 years.

24. History of Diabetes mellitus (type I or II), with the exception of gestational
diabetes.

25. History of Thyroid disease (except for well controlled hypothyroidism).

26. History of Idiopathic urticaria within the past year.

27. History of hypertension that is not well controlled by medication or that is
persistently greater than 150/95 at screening...

28. History of bleeding disorder diagnosed by a doctor (eg, factor deficiency,
coagulopathy, or platelet disorder requiring special precautions) or significant
bruising or bleeding difficulties with IM injections or blood draws.

29. History of chronic or active neurologic disease to include seizure disorder and
chronic migraine headaches. Exceptions are: i) childhood febrile seizures, or ii)
seizures secondary to alcohol withdrawal more than 3 years ago.

30. Subjects receiving any of the following substances:

- Systemic immunosuppressive medications or cytotoxic medications within 12 weeks
before enrollment [with the exception of a short course of corticosteroids (≤ 14
days duration or a single injection) for a self-limited condition at least 2
weeks before enrollment; inhaled, intranasal or topical steroids are not
considered exclusionary]

- Treatment with known immunomodulators (other than nonsteroidal anti-inflammatory
drugs [NSAIDs]) for any reason.

- History of receipt of medication that prevent or treat malaria within 1 month of
CHMI

- Live attenuated vaccines within 30 days before initial study vaccine
administration

- Medically indicated subunit or killed vaccines, eg, influenza, pneumococcal, or
allergy treatment with antigen injections, planned for administration 14 days
before or after study vaccine administration

31. History of arthritis diagnosis other than osteoarthritis.

32. History of other diagnosed rheumatoid disorders.

33. Any history of psoriasis (itchy skin rash) or porphyria (rare disturbance of
metabolism), since these conditions could get worse after treatment with chloroquine
(a medication for treating malaria).

34. Subject must not have a fever in order to receive the study vaccine or participate in
the malaria challenge.