Optimisation of Controlled Human Malaria Infection Using Sporozoites Administered by Needle and Syringe

• Sponsor: University of Oxford (Other)
• Overall Status: Completed
• CT.gov ID: NCT01465048
• Collaborator: Sanaria Inc. (Industry)
• Enrollment: 18
• Location: 1
• Arms: 3
• Duration (Months): 16.1
• Patients Per Site Per Month: 1.1

Study Details

Study Description

Brief Summary

This is an open label, human pilot study to optimise controlled human malaria infection (CHMI) administered by Plasmodium falciparum sporozoites (PfSPZ. Volunteers will be inoculated with PfSPZ Challenge. The route of administration and dose will vary in order to identify the optimal regimen that achieves the greatest infection rate in volunteers with Plasmodium falciparum. All volunteers recruited will be healthy adults aged between 18 and 45 years. Safety and infectivity data will be collected for each of the regimens.

Condition or Disease	Intervention/Treatment	Phase
Malaria; Plasmodium Falciparum	Biological: Plasmodium falciparum sporozoites 2sites; Biological: Plasmodium falciparum sporozoites 1 site; Biological: Plasmodium falciparum sporozoites 1site	N/A

Detailed Description

Studies involving CHMI are a powerful tool for investigating malaria vaccine and prophylactic drug efficacy.CHMI has now become established as a key tool to assess the efficacy of novel malaria vaccines and drugs. As CHMI trials are carried out in a controlled environment, they allow unprecedented detailed evaluation of parasite growth and immunological responses, providing essential information for vaccine and drug development.

Out of three currently available methods of performing experimental human malaria infections (blood stage infection, mosquito bites and sporozoite infection), experimental injection directly by needle and syringe using aseptic, purified, cryopreserved sporozoites is, in principle, the most accurate and practical way of dosing sporozoites for challenge studies. Recently, Sanaria Inc have been able to overcome the technical issues associated with the production of aseptic, purified, cryopreserved Plasmodium falciparum sporozoites. As a result, an Investigational New Drug application (IND) was submitted to the U.S. Food and Drug Administration in February 2009, and a Phase 1 clinical trial with experimental challenge of volunteers was initiated in April 2009. Another trial sponsored by Sanaria to find the dose of aseptic, purified, cryopreserved sporozoites that should be used for experimental human malaria infections is currently ongoing with collaboration with the Radboud University Nijmegen Medical Center, The Netherlands.

This trial will be the first time aseptic, purified, cryopreserved P. falciparum sporozoites have been administered intramuscularly to humans.

Study Design

• Study Type: Interventional
• Actual Enrollment: 18 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Official Title: A Pilot Study to Optimise Controlled Human Malaria Infections Using Plasmodium Falciparum Sporozoites Administered by Needle and Syringe
• Study Start Date: Oct 1, 2011
• Actual Primary Completion Date: Feb 1, 2012
• Actual Study Completion Date: Feb 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Plasmodium falciparum sporozoites 2sites 2,500 sporozoites intradermally	Biological: Plasmodium falciparum sporozoites 2sites; Aseptic, purified, cryopreserved Plasmodium falciparum sporozoites, 2,500 sporozoites, 50ulx2, 2 intradermal injection sites
Experimental: Plasmodium falciparum sporozoites 1 site 2,500 sporozoites intramuscularly	Biological: Plasmodium falciparum sporozoites 1 site; Aseptic, purified, cryopreserved Plasmodium falciparum sporozoites, 2,500 sporozoites, 50ulx2, 2 intramuscular injection sites
Experimental: Plasmodium falciparum sporozoites 1site 25,000 sporozoites intramuscularly	Biological: Plasmodium falciparum sporozoites 1site; Aseptic, purified, cryopreserved Plasmodium falciparum sporozoites, 25,000 sporozoites, 50ulx2, 2 intramuscular injection sites

Outcome Measures

Primary Outcome Measures

1. Number of Participants Infected [21 days post administration of PfSPZ Challenge]

   To determine the infectivity rates of PfSPZ Challenge administered in various regimens by thick film microscopy and highly sensitive PCR for Plasmodium falciparum DNA.

Secondary Outcome Measures

1. Frequency, Incidence and Nature of Adverse Events and Serious Adverse Events Arising. [Participants will be followed for the duration of the study, an expected average of 3 months]

   To assess the safety of PfSPZ Challenge administered in various regimens by analysing actively and passively collected data from clinical review of volunteers and laboratory measurements, including lab reports and adverse events.

2. Dynamics of Plasmodium Falciparum Parasite Growth Following PfSPZ Challenge Administered in Various Regimens [21 days post administration of PfSPZ Challenge]

   To determine the parasite growth dynamics of PfSPZ Challenge administered in various regimens using highly sensitive PCR for Plasmodium falciparum DNA.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 45 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Women only: Must practice continuous effective contraception for the duration of the study.

• Agreement to refrain from blood donation during the course of the study and for at least 3 years after the end of their involvement in the study.

• Written informed consent to undergo CHMI.

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

• Willingness to take a curative anti-malaria regimen.

• For volunteers not living in Oxford: agreement to stay in a hotel room close to the trial centre during a part of the study (At least Day 6.5 post inoculation until 2 days after treatment commenced).

• Answer all questions on the informed consent quiz correctly.

Exclusion Criteria:

• History of clinical P. falciparum malaria.

• Travel to a malaria endemic region during the study period or within the preceding six months with positive P. falciparum serology at screening.

• Use of systemic antibiotics with known antimalarial activity within 30 days of study enrolment (e.g. trimethoprim-sulfamethoxazole, doxycycline, tetracycline, clindamycin, erythromycin, fluoroquinolones and azithromycin)

• Receipt of an investigational product in the 30 days preceding enrollment, or planned receipt during the study period.

• Prior receipt of an investigational malaria vaccine.

• Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV infection; asplenia; recurrent, severe infections and chronic (more than 14 days) immunosuppressant medication within the past 6 months (inhaled and topical steroids are allowed).

• Use of immunoglobulins or blood products within 3 months prior to enrollment.

• History of sickle cell anemia, sickle cell trait, thalassemia or thalassemia trait.

• Pregnancy, lactation or intention to become pregnant during the study

• A history of allergic disease or reactions likely to be exacerbated by malaria infection.

• Contraindications to the use of all three proposed anti-malarial medications; Malarone, Riamet and Chloroquine.

• History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ).

• History of serious psychiatric condition that may affect participation in the study.

• Any other serious chronic illness requiring hospital specialist supervision.

• Suspected or known current alcohol abuse as defined by an alcohol intake of greater than 42 units every week.

• Suspected or known injecting drug abuse in the 5 years preceding enrollment.

• Seropositive for hepatitis B surface antigen (HBsAg).

• Seropositive for hepatitis C virus (antibodies to HCV).

• An estimated, ten year risk of fatal cardiovascular disease of ≥5%, as estimated by the Systematic Coronary Risk Evaluation (SCORE) system.39

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

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

• Any clinically significant abnormal finding on biochemistry or haematology blood tests, urinalysis or clinical examination.

• 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 participate in the study or impair interpretation of the study data.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital	Oxford		United Kingdom	OX3 7LJ

Sponsors and Collaborators

• University of Oxford
• Sanaria Inc.

Investigators

• Principal Investigator: Adrian VS Hill, DPhil FRCP, University of Oxford

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Oxford
• ClinicalTrials.gov Identifier: NCT01465048
• Other Study ID Numbers: VAC049
• First Posted: Nov 4, 2011
• Last Update Posted: Jun 24, 2013
• Last Verified: Jun 1, 2013

• Keywords provided by University of Oxford: Malaria; Protozoan Infections; Parasitic Diseases; Malaria Challenge
• Additional relevant MeSH terms: Infections; Malaria

Study Results

Participant Flow

Arm/Group Title	PfSPZ Challenge 2,500 ID	PfSPZ Challenge 2,500 IM	PfSPZ Challenge 25,000 IM
Arm/Group Description
Period Title: Overall Study
STARTED	6	6	6
COMPLETED	6	6	6
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	PfSPZ Challenge 2,500 ID	PfSPZ Challenge 2,500 IM	PfSPZ Challenge 25,000 IM	Total
Arm/Group Description	Total of all reporting groups
Overall Participants	6	6	6	18
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	6 100%	6 100%	6 100%	18 100%
>=65 years	0 0%	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	3 50%	3 50%	2 33.3%	8 44.4%
Male	3 50%	3 50%	4 66.7%	10 55.6%
Region of Enrollment (participants) [Number]
United Kingdom	6 100%	6 100%	6 100%	18 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Infected
Description	To determine the infectivity rates of PfSPZ Challenge administered in various regimens by thick film microscopy and highly sensitive PCR for Plasmodium falciparum DNA.
Time Frame	21 days post administration of PfSPZ Challenge

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	PfSPZ Challenge 2,500 ID	PfSPZ Challenge 2,500 IM	PfSPZ Challenge 25,000 IM
Arm/Group Description
Measure Participants	6	6	6
Number [Participants]	5 83.3%	3 50%	6 100%

2. Secondary Outcome

Title	Frequency, Incidence and Nature of Adverse Events and Serious Adverse Events Arising.
Description	To assess the safety of PfSPZ Challenge administered in various regimens by analysing actively and passively collected data from clinical review of volunteers and laboratory measurements, including lab reports and adverse events.
Time Frame	Participants will be followed for the duration of the study, an expected average of 3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	Dynamics of Plasmodium Falciparum Parasite Growth Following PfSPZ Challenge Administered in Various Regimens
Description	To determine the parasite growth dynamics of PfSPZ Challenge administered in various regimens using highly sensitive PCR for Plasmodium falciparum DNA.
Time Frame	21 days post administration of PfSPZ Challenge

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	07/11/11 to 13/02/12
Arm/Group Title	PfSPZ Challenge 2,500 ID		PfSPZ Challenge 2,500 IM		PfSPZ Challenge 25,000 IM
Arm/Group Description
All Cause Mortality
	PfSPZ Challenge 2,500 ID		PfSPZ Challenge 2,500 IM		PfSPZ Challenge 25,000 IM
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	PfSPZ Challenge 2,500 ID		PfSPZ Challenge 2,500 IM		PfSPZ Challenge 25,000 IM
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/6 (0%)		0/6 (0%)
Other (Not Including Serious) Adverse Events
	PfSPZ Challenge 2,500 ID		PfSPZ Challenge 2,500 IM		PfSPZ Challenge 25,000 IM
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/6 (33.3%)		2/6 (33.3%)		3/6 (50%)
General disorders
Headache	2/6 (33.3%)	2	0/6 (0%)	0	1/6 (16.7%)	1
Fever	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0
Nausea	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0
Pain	0/6 (0%)	0	0/6 (0%)	0	2/6 (33.3%)	2
Malasie	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1
Gum Bleeding	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.