Experimental Human Malaria Infection by PfSPZ

Malaria Clinical Trial

Official title:

Experimental Human Malaria Infection by Intradermal Injection of Plasmodium Falciparum Sporozoites (PfSPZ Challenge)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01086917
• Other study ID #: TIP2
• Status: Completed
• Phase: Phase 1
• First received: March 11, 2010
• Last updated: April 17, 2015
• Start date: August 2010
• Est. completion date: July 2011

Study information

• Verified date: April 2015
• Source: Sanaria Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: Ministry of Health, Welfare and SportUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The study is a single center, varied dose, open label study. A maximum of eighteen volunteers will be exposed to live NF54 P. falciparum sporozoites (PfSPZ Challenge) by intradermal injection. Volunteers will be divided into three groups of 6 volunteers, each group spaced 25 days apart (21 days after the last challenge of the last volunteer from the previous dose group).

Description:

In every group on day 1, two volunteers will be injected. On day 3 the remaining four volunteers of the group will be injected. Injections in subsequent volunteers are always spaced at least one hour apart in any group. Injection of subsequent (groups of) volunteers will only commence if the previous injection was shown to be safe. Three different doses of PfSPZ will be administered: a dose of 2,500 PfSPZ Challenge (Group 1); a dose of 10,000 PfSPZ Challenge (Group 2) if not all volunteers become thick smear positive (TS+) in Group 1; and a dose of 25,000 PfSPZ Challenge (Group 3) if there is not 100% TS+ in Group 2. If all volunteers in Group 1 (2,500 PfSPZ Challenge) become thick smear positive, then Group 2a will receive 1,000 PfSPZ Challenge. If all volunteers in Group 2a become TS+, the volunteers in Group 3a will receive 500 PfSPZ Challenge. If all volunteers in Group 2 (10,000 PfSPZ Challenge) become TS+, Group 3b will receive 5,000 PfSPZ. If less than 100% of volunteers in Group 2a (1,000 PfSPZ Challenge) become TS+ then Group 3c will receive 1,750 PfSPZ Challenge.

The clinical, biological, parasitological and immunological data of these groups' volunteers will be compared. Volunteers and the investigator will not be blinded, but the laboratory personnel will be blinded.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: July 2011
• Est. primary completion date: February 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 19 Years to 34 Years

Eligibility

Inclusion Criteria:

1. Age > 18 and < 35 years healthy volunteers (males or females)

2. Good health based on history and clinical examination

3. Negative pregnancy test

4. Use of adequate contraception for females

5. All volunteers must sign the informed consent form demonstrating their understanding of the meaning and procedures of the study

6. Volunteer agrees to inform the general practitioner and agrees to sign a request to release medical information concerning contra-indications for participation in the study

7. Willingness to undergo a Pf sporozoite challenge

8. For volunteers not living in Nijmegen: agreement to stay in a hotel room close to the trial center during a part of the study (Day 5 till 3 days after treatment)

9. Reachable (24/7) by mobile phone during the whole study period

10. Living with a third party that could contact the clinicians in case of alteration of consciousness or agreement to stay in a hotel room close to the trial center during a part of the study (Day 5 till 3 days after treatment)

11. Available to attend all study visits

12. Agreement to refrain from blood donation to Sanquin or for other purposes, during the study period until day 140.

13. Willingness to undergo HIV, hepatitis B and hepatitis C tests

14. Negative urine toxicology screening test at screening visit and day before challenge

15. Willingness to take a curative regimen of Malarone®

Exclusion Criteria:

1. History of malaria

2. Plans to travel to malaria endemic areas during the 140 day study period

3. Plans to travel outside of the Netherlands during day 0-28 of the study

4. Previous participation in any malaria vaccine study and/or positive serology for Pf

5. Symptoms, physical signs and laboratory values suggestive of systemic disorders including renal, hepatic, cardiovascular, pulmonary, skin, immunodeficiency, psychiatric, and other conditions which could interfere with the interpretation of the study results or compromise the health of the volunteers

6. History of diabetes mellitus or cancer (except basal cell carcinoma of the skin)

7. History of arrhythmias or prolonged QT-interval

8. Positive family history in 1st and 2nd degree relatives for cardiac disease < 50 years old

9. An estimated, ten year risk of fatal cardiovascular disease of =5%, as estimated by the Systematic Coronary Risk Evaluation (SCORE) system

10. Clinically significant abnormalities in electrocardiogram (ECG) at screening

11. Body Mass Index (BMI) below 18 or above 30 kg/m2

12. Any clinically significant deviation from the normal range in biochemistry or hematology blood tests or in urine analysis

13. Positive HIV, HBV or HCV tests

14. Participation in any other clinical study within 30 days prior to the onset of the study

15. Enrollment in any other clinical study during the study period

16. Pregnant or lactating women

17. Volunteers unable to give written informed consent

18. Volunteers unable to be closely followed for social, geographic or psychological reasons

19. Previous history of drug or alcohol abuse interfering with normal social function during a period of one year prior to enrolment in the study

20. A history of psychiatric disease

21. Known hypersensitivity to anti-malaria drugs

22. The use of chronic immunosuppressive drugs, antibiotics, or other immune modifying drugs within three months of study onset (inhaled and topical corticosteroids are allowed) and during the study period

23. Contra-indications to Malarone® including treatment taken by the volunteer that interferes with Malarone®

24. Any confirmed or suspected immunosuppressive or immunodeficient condition, including asplenia

25. Co-workers of the departments of Medical Microbiology or Internal Medicine of the Radboud University Nijmegen Medical Centre or Sanaria Inc.

26. A history of sickle cell anemia, sickle cell trait, thalassemia , thalassemia trait or G6PD deficiency

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Malaria

Intervention

Biological:
• PfSPZ Challenge
each volunteer to receive a single dose

Locations

Country	Name	City	State
Netherlands	Radboud University Nijmegen Medical Center	Nijmegen

Sponsors (2)

Lead Sponsor	Collaborator
Sanaria Inc.	Radboud University

Country where clinical trial is conducted

Netherlands, 

References & Publications (1)

Roestenberg M, Bijker EM, Sim BK, Billingsley PF, James ER, Bastiaens GJ, Teirlinck AC, Scholzen A, Teelen K, Arens T, van der Ven AJ, Gunasekera A, Chakravarty S, Velmurugan S, Hermsen CC, Sauerwein RW, Hoffman SL. Controlled human malaria infections by — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of volunteers with Plasmodium falciparum Infection	To achieve a 100% infection rate of human volunteers by intradermal injection of aseptic, purified, cryopreserved Pf sporozoites (PfSPZ Challenge)as measured by 100% thick smear positivity (thick blood smears) of all volunteers from one group	Upto 7 months	No
Secondary	Kinetics of infection	To compare parasite kinetics between different doses of intradermal injection of PfSPZ Challenge as measured by: A significant difference in time of thick smear positivity between the groups of volunteers; A significant quantitative difference in parasitemia as measured by retrospective PCR between the groups of volunteers; A significant difference in kinetics of parasitemia between the groups of volunteers as measured by retrospective PCR; A difference in occurrence or intensity of signs or symptoms between the groups of volunteers	Upto 7 months	No