Phase I/II Trial of a Malaria Vaccine in Adults Living in the United States of America

• Sponsor: U.S. Army Medical Research and Development Command (U.S. Fed)
• Overall Status: Completed
• CT.gov ID: NCT00312702
• Collaborator: GlaxoSmithKline (Industry), The PATH Malaria Vaccine Initiative (MVI) (Other), Walter Reed Army Institute of Research (WRAIR) (U.S. Fed)
• Enrollment: 18
• Location: 1
• Arms: 2
• Duration (Months): 12
• Patients Per Site Per Month: 1.5

Study Details

Study Description

Brief Summary

Phase I/II Trial of a Malaria Vaccine, FMP011/AS01B, in Adults Living in the United States of America.

Condition or Disease	Intervention/Treatment	Phase
Malaria; Plasmodium Falciparum Malaria	Biological: Falciparum Malaria Protein 11 with AS02A adjuvant	Phase 1/Phase 2

Detailed Description

• Controlled challenge, Phase I/IIa WRAIR study.

• Healthy, malaria-naive adults aged 18 - 50 years.

• 2 groups, 5 subjects in group A (10µg dose) and 15 subjects in group B (50µg dose).

• Control: none for immunization phase; infectivity controls for challenge and rechallenge phases. Six infectivity controls per day of challenge will be enrolled for the challenge phases, with 3 alternates available for challenge if needed.

• Vaccination schedule of 0, 1 months.

• Challenge of up to 15 subjects in Group B.

• Contingent upon short term efficacy, rechallenge of initially protected subjects 6 months (+/- 2 months) after second dose of vaccine.

• Self-contained study.

• Duration of the study, per subject: approximately 15 months (screening, enrollment, vaccination, challenge and rechallenge).

• Data collection will be by done at the site.

Study Design

• Study Type: Interventional
• Actual Enrollment: 18 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: A Phase I/IIa Controlled Study of the Safety, Immunogenicity and Preliminary Efficacy of FMP011/AS02A Candidate Malaria Vaccine in Malaria-naive Adults Living in the United States
• Study Start Date: Apr 1, 2006
• Actual Primary Completion Date: Oct 1, 2006
• Actual Study Completion Date: Apr 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 10µg dose FMP011 Falciparum Malaria Protein 11 with AS02A adjuvant	Biological: Falciparum Malaria Protein 11 with AS02A adjuvant; vaccine
Experimental: 50µg dose FMP011 Falciparum Malaria Protein 11 with AS02A adjuvant	Biological: Falciparum Malaria Protein 11 with AS02A adjuvant; vaccine

Outcome Measures

Primary Outcome Measures

1. Safety - Most Frequently Reported Adverse Events and Grade [30 days post vaccination]

   An AE was defined as any reaction, side effect, or untoward event that occurred during the course of the trial whether or not the event was considered related to study drug or clinically significant. Grade 1: Mild Grade 2: Moderate Grade 3: Severe

Secondary Outcome Measures

1. Anti-LSA-1 Antibody Response in Titer Units [days 0, 28, 42 (challenge day) and 84]

   Anti-LSA-1 Antibody Response in Titer Units on days 0, 28, 42 and 84

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 50 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• A male or non-pregnant female 18 to 50 years of age (inclusive) at the time of screening.

• Written informed consent obtained from the subject before screening procedures.

• Free of obvious health problems as established by medical history and clinical examination before entering into the study.*

• Available to participate for duration of study (approximately 15 months).

• If the subject is female, she must be currently using birth control, must be surgically sterilized, or must be at least 1-year post menopausal.

• Pass a comprehension assessment test.

Exclusion Criteria:

• Prior receipt of an investigational malaria vaccine.

• Use of any investigational or non-registered drug or vaccine other than the study vaccine(s) within 28 days preceding the first dose of study vaccine, or planned use during the study period.

• Administration of chronic immunosuppressants or other immune modifying drugs within six months of vaccination.

• Chronic use of antibiotics with anti-malarial effects.

• Planned administration/ administration of a vaccine not foreseen by the study protocol within 30 days of the first dose of vaccine(s).

• History of use of anti-malarial medication within 60 days prior to vaccination.

• Any history of malaria.

• Known exposure to malaria within the previous 12 months.

• Planned travel to malarious areas during the study period.

• Any confirmed or suspected immunosuppressive or immunodeficient condition, including HIV infection.

• A family history of congenital or hereditary immunodeficiency.

• History of allergic disease or reactions likely to be exacerbated by any component of the vaccine.

• Chronic or active neurologic disease including seizures, but not including a single febrile seizure as a child.

• History of splenectomy.

• Acute disease at the time of enrollment.

• Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests.

• Personal history of autoimmune disease or subjects who describe a first-degree relative with clearly documented autoimmune disease.

• Seropositive for hepatitis B surface antigen.

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

• Administration of immunoglobulins and/or any blood products within the three months preceding the first dose of study vaccine or planned administration during the study period.

• Pregnant or lactating female.

• Suspected or known current alcohol abuse as defined by the American Psychiatric Association in DSM IV.

• Chronic or active intravenous drug use.

• History of severe reactions to mosquito bites as defined as anaphylaxis.

• Female who intends to become pregnant during the study.

• Any history of anaphylaxis in reaction to vaccination.

• A clinical history of sickle cell disease or sickle cell trait.

• Any other significant finding that in the opinion of the investigator would increase the risk of having an adverse outcome from participating in this study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Walter Reed Army Institute of Research	Silver Spring	Maryland	United States	20910

Sponsors and Collaborators

• U.S. Army Medical Research and Development Command
• GlaxoSmithKline
• The PATH Malaria Vaccine Initiative (MVI)
• Walter Reed Army Institute of Research (WRAIR)

Investigators

• Principal Investigator: James F Cummings, MD, Walter Reed Army Institute of Research (WRAIR)

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: U.S. Army Medical Research and Development Command
• ClinicalTrials.gov Identifier: NCT00312702
• Other Study ID Numbers: WRAIR 1249; HSRRB A-13732
• First Posted: Apr 10, 2006
• Last Update Posted: Nov 26, 2018
• Last Verified: May 1, 2018

• Keywords provided by U.S. Army Medical Research and Development Command: Vaccine; Malaria; Liver Stage Antigen-1; Falciparum Malaria Protein-11; AS02A; adjuvant
• Additional relevant MeSH terms: Malaria; Malaria, Falciparum

Study Results

Participant Flow

Recruitment Details	18 immunized, 12 IC's from high dose group and 6 control subject
Pre-assignment Detail	18 subjects were randomly assigned to the immunization phase for each of the 2 vaccine formulations. 12 IC's from high does group and 1 non immunized infectivity control subject out of the 6 came from this phase 1 study, the other 5 came from the phase 2 study (WRAIR 1250, NCT00312663). Both studies were included in one final clinical study report.

Arm/Group Title	10µg Dose FMP011	50µg Dose FMP011	Infectivity Controls (IC)
Arm/Group Description	Falciparum Malaria Protein 11 with AS02A adjuvant Falciparum Malaria Protein 11 with AS02A adjuvant: vaccine	Falciparum Malaria Protein 11 with AS02A adjuvant Falciparum Malaria Protein 11 with AS02A adjuvant: vaccine	12 Subjects from the high dose group and 1 non immunized subject enrolled prior to challenge to serve as IC's for malaria sporozoite challenge. 1 infectivity control subject out of the 6 came from this phase 1 study, the other 5 came from the phase 2 study (WRAIR 1250, NCT00312663). Both studies were included in one final clinical study report.
Period Title: Immunization Phase
STARTED	5	13	0
COMPLETED	5	12	0
NOT COMPLETED	0	1	0
Period Title: Immunization Phase
STARTED	0	12	1
COMPLETED	0	12	1
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	10µg Dose FMP011	50µg Dose FMP011	Infectivity Control (IC)	Total
Arm/Group Description	Falciparum Malaria Protein 11 with AS02A adjuvant Falciparum Malaria Protein 11 with AS02A adjuvant: vaccine	Falciparum Malaria Protein 11 with AS02A adjuvant Falciparum Malaria Protein 11 with AS02A adjuvant: vaccine	12 Subjects from the high dose group and 1 non immunized subject enrolled prior to challenge to serve as IC's for malaria sporozoite challenge. 1 infectivity control subject out of the 6 came from this phase 1 study, the other 5 came from the phase 2 study (WRAIR 1250, NCT00312663). Both studies were included in one final clinical study report.	Total of all reporting groups
Overall Participants	5	13	1	19
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	25.4 (6.2)	32.8 (8.2)	34.5 (0.0)	30.7 (8.2)
Sex: Female, Male (Count of Participants)
Female	2 40%	7 53.8%	1 100%	10 52.6%
Male	3 60%	6 46.2%	0 0%	9 47.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%	0 0%
Not Hispanic or Latino	5 100%	13 100%	1 100%	19 100%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	1 7.7%	0 0%	1 5.3%
Asian	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%
White	5 100%	11 84.6%	1 100%	17 89.5%
More than one race	0 0%	1 7.7%	0 0%	1 5.3%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	5 100%	13 100%	1 100%	18 94.7%

Outcome Measures

1. Primary Outcome

Title	Safety - Most Frequently Reported Adverse Events and Grade
Description	An AE was defined as any reaction, side effect, or untoward event that occurred during the course of the trial whether or not the event was considered related to study drug or clinically significant. Grade 1: Mild Grade 2: Moderate Grade 3: Severe
Time Frame	30 days post vaccination

Outcome Measure Data

Analysis Population Description

The AE's were tabulated and summarized by subject and treatment groups. No additional analyses were performed. Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe Infectivity Controls were not included in this analysis.

Arm/Group Title	10µg Dose FMP011	50µg Dose FMP011	Infectivity Control
Arm/Group Description	Falciparum Malaria Protein 11 with AS02A adjuvant Falciparum Malaria Protein 11 with AS02A adjuvant: vaccine	Falciparum Malaria Protein 11 with AS02A adjuvant Falciparum Malaria Protein 11 with AS02A adjuvant: vaccine	12 Subjects from the high dose group and 1 non immunized subject enrolled prior to challenge to serve as IC's for malaria sporozoite challenge. 1 infectivity control subject out of the 6 came from this phase 1 study, the other 5 came from the phase 2 study (WRAIR 1250, NCT00312663). Both studies were included in one final clinical study report.
Measure Participants	5	13	1
Pain - Grade 1	3	10	0
Pain - Grade 2	2	3	0
Pain - Grade 3	0	0	0
Redness - Grade 1	3	1	0
Redness - Grade 2	0	0	0
Redness - Grade 3	0	1	0
Swelling - Grade 1	1	1	0
Swelling - Grade 2	0	1	0
Swelling - Grade 3	0	0	0

2. Secondary Outcome

Title	Anti-LSA-1 Antibody Response in Titer Units
Description	Anti-LSA-1 Antibody Response in Titer Units on days 0, 28, 42 and 84
Time Frame	days 0, 28, 42 (challenge day) and 84

Outcome Measure Data

Analysis Population Description

Low dose group didn't participate in challenge (day 42) and day 84

Arm/Group Title	10µg Dose FMP011	50µg Dose FMP011
Arm/Group Description	Falciparum Malaria Protein 11 with AS02A adjuvant Falciparum Malaria Protein 11 with AS02A adjuvant: vaccine	Falciparum Malaria Protein 11 with AS02A adjuvant Falciparum Malaria Protein 11 with AS02A adjuvant: vaccine
Measure Participants	5	13
Day 0	24.8	47.1
Day 28	1629.9	834.8
Day 42 (challenge day)	NA	29851.5
Day 84	NA	10378.5

Adverse Events

Time Frame	Up to 6 months
Adverse Event Reporting Description	Evaluate the safety by 1) the occurrence of solicited AEs over a 7 day follow-up period (day of immunization and 6 days post-immunization); 2) the occurrence of unsolicited AEs over a 30 day follow-up period (day of immunization and 29 day follow-up period ); and 3) the occurrence of SAE's during the study period. Subjects in the Infectivity Control group were not included in this analysis and are not presented in the final clinical study report.
Arm/Group Title	10µg Dose FMP011		50µg Dose FMP011		Infecticvity Control (IC)
Arm/Group Description	Falciparum Malaria Protein 11 with AS02A adjuvant Falciparum Malaria Protein 11 with AS02A adjuvant: vaccine		Falciparum Malaria Protein 11 with AS02A adjuvant Falciparum Malaria Protein 11 with AS02A adjuvant: vaccine		12 Subjects from the high dose group and 1 non immunized subject enrolled prior to challenge to serve as IC's for malaria sporozoite challenge. 1 infectivity control subject out of the 6 came from this phase 1 study, the other 5 came from the phase 2 study (WRAIR 1250, NCT00312663). Both studies were included in one final clinical study report.
All Cause Mortality
	10µg Dose FMP011		50µg Dose FMP011		Infecticvity Control (IC)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/13 (0%)		0/1 (0%)
Serious Adverse Events
	10µg Dose FMP011		50µg Dose FMP011		Infecticvity Control (IC)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/13 (0%)		0/1 (0%)
Other (Not Including Serious) Adverse Events
	10µg Dose FMP011		50µg Dose FMP011		Infecticvity Control (IC)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/5 (100%)		13/13 (100%)		0/1 (0%)
Blood and lymphatic system disorders
Axilla lymphadenopathy	1/5 (20%)	1	0/13 (0%)	0	0/1 (0%)	0
Axilla lymphadenopathy	1/5 (20%)	1	0/13 (0%)	0	0/1 (0%)	0
Ear and labyrinth disorders
Ringing in ears - bilateral	0/5 (0%)	0	1/13 (7.7%)	1	0/1 (0%)	0
Ringing in ears - bilateral	0/5 (0%)	0	1/13 (7.7%)	1	0/1 (0%)	0
Gastrointestinal disorders
Nausea	0/5 (0%)	0	4/13 (30.8%)	4	0/1 (0%)	0
Nausea	0/5 (0%)	0	4/13 (30.8%)	4	0/1 (0%)	0
General disorders
Local	5/5 (100%)	5	13/13 (100%)	13	0/1 (0%)	0
Pain	5/5 (100%)	5	13/13 (100%)	13	0/1 (0%)	0
Swelling	1/5 (20%)	1	2/13 (15.4%)	2	0/1 (0%)	0
Fever	1/5 (20%)	1	1/13 (7.7%)	1	0/1 (0%)	0
Malaise	2/5 (40%)	2	6/13 (46.2%)	6	0/1 (0%)	0
Fatigue	3/5 (60%)	3	6/13 (46.2%)	6	0/1 (0%)	0
Local	5/5 (100%)	5	13/13 (100%)	13	0/1 (0%)	0
Pain	5/5 (100%)	5	13/13 (100%)	13	0/1 (0%)	0
Swelling	1/5 (20%)	1	2/13 (15.4%)	2	0/1 (0%)	0
Fever	1/5 (20%)	1	0/13 (0%)	0	0/1 (0%)	0
Fatigue	1/5 (20%)	1	2/13 (15.4%)	2	0/1 (0%)	0
Local	5/5 (100%)	5	10/13 (76.9%)	10	0/1 (0%)	0
Pain	5/5 (100%)	5	9/13 (69.2%)	9	0/1 (0%)	0
Swelling	0/5 (0%)	0	1/13 (7.7%)	1	0/1 (0%)	0
Fever	1/5 (20%)	1	1/13 (7.7%)	1	0/1 (0%)	0
Malaise	2/5 (40%)	2	6/13 (46.2%)	6	0/1 (0%)	0
Fatigue	2/5 (40%)	2	6/13 (46.2%)	6	0/1 (0%)	0
Injury, poisoning and procedural complications
Bruise at injection site	0/5 (0%)	0	1/13 (7.7%)	1	0/1 (0%)	0
Bruise at injection site	0/5 (0%)	0	1/13 (7.7%)	1	0/1 (0%)	0
Musculoskeletal and connective tissue disorders
Myalgia	2/5 (40%)	2	4/13 (30.8%)	4	0/1 (0%)	0
Myalgia	0/5 (0%)	0	1/13 (7.7%)	1	0/1 (0%)	0
Myalgia	2/5 (40%)	2	4/13 (30.8%)	4	0/1 (0%)	0
Chills	0/5 (0%)	0	2/13 (15.4%)	2	0/1 (0%)	0
Nervous system disorders
Headache	1/5 (20%)	1	5/13 (38.5%)	5	0/1 (0%)	0
Headache	1/5 (20%)	1	5/13 (38.5%)	5	0/1 (0%)	0
Vasovagal event	0/5 (0%)	0	1/13 (7.7%)	1	0/1 (0%)	0
Vasovagal event	0/5 (0%)	0	1/13 (7.7%)	1	0/1 (0%)	0
Skin and subcutaneous tissue disorders
Redness	3/5 (60%)	3	2/13 (15.4%)	2	0/1 (0%)	0
Redness	3/5 (60%)	3	2/13 (15.4%)	2	0/1 (0%)	0
Redness	0/5 (0%)	0	1/13 (7.7%)	1	0/1 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.