FMP2.1/AS02A: Rabies Vaccine Malaria-Experienced Adults in Bandiagara, Mali

• Sponsor: U.S. Army Medical Research and Development Command (U.S. Fed)
• Overall Status: Completed
• CT.gov ID: NCT00349713
• Collaborator: National Institute of Allergy and Infectious Diseases (NIAID) (NIH), Walter Reed Army Institute of Research (WRAIR) (U.S. Fed), GlaxoSmithKline (Industry), University of Maryland (Other)
• Enrollment: 60
• Location: 1
• Arms: 3
• Duration (Months): 25
• Patients Per Site Per Month: 2.4

Study Details

Study Description

Brief Summary

Malaria is a disease that affects many people in Africa and in Mali. It is caused by germs that are spread by mosquito bites. This study will look at the safety, effectiveness, and best dose of an experimental malaria vaccine in people who are regularly exposed to malaria. Study participants will be 60 adults, 18-55 years old, who live in Bandiagara, Mali. Volunteers will get either 3 full doses of the experimental malaria vaccine, 3 half doses of the malaria vaccine, or a rabies vaccine that has been approved in Mali. (Rabies is an infection of the brain that usually causes death, and can be caught from being bitten by infected dogs or bats.) The 3 vaccinations will be given by injection into the upper arm 30 days apart. Volunteers will be enrolled in the study for approximately 12 months after the first vaccination. Volunteers will have 14 blood samples collected during the study for testing to make sure that the vaccine is not harmful and to measure the effect of the vaccine.

Condition or Disease	Intervention/Treatment	Phase
Malaria; Plasmodium Falciparum Malaria	Biological: FMP2.1/AS02A; Biological: Rabies vaccine (RabAvert)	Phase 1

Detailed Description

The primary objective of this study is to evaluate the safety and reactogenicity of two dose levels of WRAIR's AMA1 malaria antigen (FMP2.1) adjuvanted in GlaxoSmithKline Biologicals' AS02A compared to rabies vaccine in malaria-experienced Malian adults aged 18-55 years inclusive. Secondary objectives are to: (1) measure the magnitude and duration of antibody response to FMP2.1; (2) measure cellular immune responses to FMP2.1 at baseline and after immunization; (3) measure the inhibition of parasite growth by the in vitro GIA; and (4) determine the specificity of the antibodies to diverse AMA1 genotypes in addition to 3D7, by measuring by ELISA, and GIA on parasites with typed AMA1. A double-blind controlled dose escalation trial will allow assessment of vaccine safety in each of three groups, one group each to receive medium and full dose levels of the experimental vaccine, and one group to receive the comparator vaccine. Thirty adults will be randomized to receive the medium dose level of FMP2.1 (n=20) or rabies vaccine (n=10) and thirty to receive the full dose level of FMP2.1 (n=20) or rabies vaccine (n=10). The division of the rabies group into two groups of ten is done to maintain blinding at each immunization time point, and all participants who receive the rabies vaccine will be analyzed as a single group. The sample size of the groups, however, will not allow detection of anything other than very large differences in the occurrence of adverse events among the three groups. The advantage of double blinding is to remove the potential for investigator and participant prejudgment about the effects of the vaccines in the reporting of adverse events.

Study Design

• Study Type: Interventional
• Actual Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Prevention
• Official Title: Double Blind Randomized, Controlled Phase 1 Dose Escalation Trial to Evaluate the Safety and Immunogenicity of the WRAIR AMA1 Malaria Antigen (FMP2.1) Adjuvanted in GSK's AS02A Versus Rabies Vaccine in Malaria-experienced Adults in Bandiagara, Mali
• Study Start Date: Nov 1, 2004
• Actual Primary Completion Date: Dec 1, 2005
• Actual Study Completion Date: Dec 1, 2006

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1: 25ug FMP2.1 / AS02A 20 subject to receive 25ug of FMP2.1 vaccine in 0.25mL of GSK Biologicals' adjuvant AS02A	Biological: FMP2.1/AS02A; FMP2.1 in GSK Biologicals' AS02A
Experimental: Cohort 2: 50ug FMP2.1 / AS02A 20 subjects to receive 50ug of FMP2.1 vaccine in 0.5mL of GSK Biologicals' adjuvant AS02A	Biological: FMP2.1/AS02A; FMP2.1 in GSK Biologicals' AS02A
Active Comparator: Cohorts 1 and 2: Rabies vaccine (RabAvert) 20 subjects to receive Rabies vaccine (RabAvert). 10 subjects from Cohort 1 and 10 subjects from Cohort 2 Rabies vaccine (RabAvert): RabAvert Rabies vaccine	Biological: FMP2.1/AS02A; FMP2.1 in GSK Biologicals' AS02A; Biological: Rabies vaccine (RabAvert); RabAvert Rabies vaccine

Outcome Measures

Primary Outcome Measures

1. Safety and Reactogenicity (SAEs and AEs) [12 months]

   The primary objective was to evaluate the safety and reactogenicity of 2 dose levels of WRAIR's AMA1 malaria antigen (FMP2.1) adjuvanted in GlaxoSmithKline Biologicals' (GSK) AS02A compared to rabies vaccine in malaria-experienced Malian adults aged 18-55 years inclusive. Solicated AEs were recorded for the 7 day surveillance period after each vaccination. Unsolicited AEs were recorded for 30 days after each vaccination.

Secondary Outcome Measures

1. Antibody Response to FMP2.1 Over Time [90 Days]

   Measurement of anti-AMA1 antibody titers over time

2. Anti-AMA1 Log Antibody Titers Over Time [90 Days]

   Summary of Anti-AMA1 Log Antibody titers on days 0, 14, 30, 44, 60, 74 and 90

3. Geometric Mean Antibody Titers Over Time [90 Days]

   Measurement of geometric mean antibody titers on days 0, 14, 30, 44, 60, 74 and 90

4. Subjects With 2- and 4-fold Increases in Anti-FMP2.1 Antibody Levels Over Time [90 Days]

   Proportion of Subjects with 2- and 4-fold increases in Anti-FMP2.1 Antibody levels on days 14, 30, 44, 60, 74 and 90

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

1. A male or non-pregnant female aged 18-55 years inclusive at the time of screening

2. For women, willingness not to become pregnant until 1 month after the last immunization (pre-menopausal female participants will be referred to the local family planning clinic in Bandiagara, which offers several means of contraception that are approved and recommended by the Malian Ministry of Health)

3. Separate written informed consent obtained from the participant before screening and study start, respectively

4. Available and willing to participate in follow-up for the duration of study (12 months)

Exclusion Criteria:

1. Previous vaccination with any investigational vaccine or with any rabies vaccine

2. Use of any investigational or non-registered drug or vaccine other than the study vaccine(s) within 30 days preceding the first study immunization, or planned use up to 30 days after the third immunization

3. Chronic administration (defined as more than 14 days) of immuno-suppressants or other immune-modifying drugs within six months prior to the first immunization. This will include any dose level of oral steroids or inhaled steroids, but not topical steroids

4. Planned administration/administration of a vaccine not foreseen by the study protocol within 30 days before the first study immunization with the exception of tetanus toxoid

5. Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection

6. Any confirmed or suspected autoimmune disease

7. History of allergic reactions or anaphylaxis to immunizations or to any vaccine component

8. History of serious allergic reactions to any substance, requiring hospitalization or emergent medical care

9. History of allergy to tetracycline, doxycycline, nickel, Imidazole, chicken eggs, processed bovine gelatin, chicken protein, neomycin, or amphotericin B

10. History of splenectomy

11. Serum ALT >/=43 IU/L

12. Serum creatinine level >113 µmol /L for males and 70 µmol /L for females

13. Hgb <11 g/dL for males and <10 g/dL for females

14. WBC <4.0 x 1000/cubic mm or >13 x 1000/cubic mm

15. Absolute lymphocyte count </=1.4 x 1000 /µl

16. Thrombocytopenia < 108,000/µl

17. More than trace protein, more than trace hemoglobin or positive glucose in urine

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

19. Suspected or known current alcohol or illicit drug abuse

20. Pregnancy or positive urine beta-HCG on the day of or prior to immunization

21. Breastfeeding

22. Simultaneous participation in any other interventional clinical trial

23. Acute or chronic pulmonary, cardiovascular, hepatic, renal or neurological condition, or any other findings that in the opinion of the Principal Investigator (PI) may increase the risk of participating in the study

24. Other condition that in the opinion of the PI would jeopardize the safety or rights of a participant in the trial or would render the participant unable to comply with the protocol

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Bamako, Malaria Research and Training Center	Bamako		Mali

Sponsors and Collaborators

• U.S. Army Medical Research and Development Command
• National Institute of Allergy and Infectious Diseases (NIAID)
• Walter Reed Army Institute of Research (WRAIR)
• GlaxoSmithKline
• University of Maryland

Investigators

• Principal Investigator: Mahamadou A. Thera, M.D., University of Bamako
• Principal Investigator: Chris V. Plowe, M.D., University of Maryland School of Medicine

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: U.S. Army Medical Research and Development Command
• ClinicalTrials.gov Identifier: NCT00349713
• Other Study ID Numbers: 04-031; N01AI085346-006; N01AI085346-005; N01AI085346-000; 102231 ( Malaria-037); HSRRB A-12855
• First Posted: Jul 10, 2006
• Last Update Posted: Jul 24, 2017
• Last Verified: Apr 1, 2017

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by U.S. Army Medical Research and Development Command: Plasmodium falciparum Malaria, Mali, adjuvant
• Additional relevant MeSH terms: Malaria; Malaria, Falciparum

Study Results

Participant Flow

Recruitment Details	175 participants were screened; 115 were excluded; 60 subjects were randomized in a 2:1 ratio into 2 cohorts

Arm/Group Title	Cohort 1: FMP2.1 / AS02A	Cohort 2: FMP2.1 / AS02A	Cohorts 1 and 2: Rabies Vaccine (RabAvert)
Arm/Group Description	20 subject to receive 25ug of FMP2.1 vaccine in 0.25mL of GSK Biologicals' adjuvant AS02A FMP2.1/AS02A: FMP2.1 in GSK Biologicals' AS02A	20 subjects to receive 50ug of FMP2.1 vaccine in 0.5mL of GSK Biologicals' adjuvant AS02A FMP2.1/AS02A: FMP2.1 in GSK Biologicals' AS02A	20 subjects to receive Rabies vaccine (RabAvert). 10 subjects from Cohort 1 and 10 subjects from Cohort 2 Rabies vaccine (RabAvert): RabAvert Rabies vaccine
Period Title: Overall Study
STARTED	20	20	20
COMPLETED	20	20	20
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Cohort 1: 25ug FMP2.1 / AS02A	Cohort 2: 50ug FMP2.1 / AS02A	Cohorts 1 and 2: Rabies Vaccine (RabAvert)	Total
Arm/Group Description	20 subject to receive 25ug of FMP2.1 vaccine in 0.25mL of GSK Biologicals' adjuvant AS02A FMP2.1/AS02A: FMP2.1 in GSK Biologicals' AS02A	20 subjects to receive 50ug of FMP2.1 vaccine in 0.5mL of GSK Biologicals' adjuvant AS02A FMP2.1/AS02A: FMP2.1 in GSK Biologicals' AS02A	20 subjects to receive Rabies vaccine (RabAvert). 10 subjects from Cohort 1 and 10 subjects from Cohort 2 Rabies vaccine (RabAvert): RabAvert Rabies vaccine	Total of all reporting groups
Overall Participants	20	20	20	60
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	20 100%	20 100%	20 100%	60 100%
>=65 years	0 0%	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	4 20%	4 20%	3 15%	11 18.3%
Male	16 80%	16 80%	17 85%	49 81.7%
Region of Enrollment (Count of Participants)
Mali	20 100%	20 100%	20 100%	60 100%

Outcome Measures

1. Primary Outcome

Title	Safety and Reactogenicity (SAEs and AEs)
Description	The primary objective was to evaluate the safety and reactogenicity of 2 dose levels of WRAIR's AMA1 malaria antigen (FMP2.1) adjuvanted in GlaxoSmithKline Biologicals' (GSK) AS02A compared to rabies vaccine in malaria-experienced Malian adults aged 18-55 years inclusive. Solicated AEs were recorded for the 7 day surveillance period after each vaccination. Unsolicited AEs were recorded for 30 days after each vaccination.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

Summary of Adverse Events by Group and Immunization Group

Arm/Group Title	Cohort 1: 25ug FMP2.1 / AS02A	Cohort 2: 50ug FMP2.1 / AS02A	Cohorts 1 and 2: Rabies Vaccine (RabAvert)
Arm/Group Description	20 subject to receive 25ug of FMP2.1 vaccine in 0.25mL of GSK Biologicals' adjuvant AS02A FMP2.1/AS02A: FMP2.1 in GSK Biologicals' AS02A	20 subjects to receive 50ug of FMP2.1 vaccine in 0.5mL of GSK Biologicals' adjuvant AS02A FMP2.1/AS02A: FMP2.1 in GSK Biologicals' AS02A	20 subjects to receive Rabies vaccine (RabAvert). 10 subjects from Cohort 1 and 10 subjects from Cohort 2 Rabies vaccine (RabAvert): RabAvert Rabies vaccine
Measure Participants	20	20	20
Solicited: Injection Site Pain	45	53	22
Solicited: Injection Site Swelling	37	35	11
Solicited: Arm Motion Limitation	5	3	0
Solicited: Elevated Temperature	6	6	1
Solicited: Headache	7	17	9
Solicited: Chills	4	2	4
Solicited: Malaise	4	5	3
Solicited: Nausea	4	1	1
Solicited: Arthralgia	0	2	1
Solicited: Myalgia	3	6	3
Solicited: Erythema	0	0	0
Unsolicited: Cold	21	10	7
Unsolicited: Headaches	11	11	5
Unsolicited: Coughing	8	3	3
Unsolicited: Flu	6	3	3
Unsolicited: Wound	3	2	4
Unsolicited: Myalgia	2	2	4
Unsolicited: Scratch	1	2	3
Unsolicited: Diarrhea	1	2	3
Unsolicited: Pruritus	1	4	1

2. Secondary Outcome

Title	Antibody Response to FMP2.1 Over Time
Description	Measurement of anti-AMA1 antibody titers over time
Time Frame	90 Days

Outcome Measure Data

Analysis Population Description

Anti-AMA1 Antibody titers on days, 0, 14, 30, 44, 60, 74, and 90

Arm/Group Title	Cohort 1: 25ug FMP2.1 / AS02A	Cohort 2: 50ug FMP2.1 / AS02A	Cohorts 1 and 2: Rabies Vaccine (RabAvert)
Arm/Group Description	20 subject to receive 25ug of FMP2.1 vaccine in 0.25mL of GSK Biologicals' adjuvant AS02A FMP2.1/AS02A: FMP2.1 in GSK Biologicals' AS02A	20 subjects to receive 50ug of FMP2.1 vaccine in 0.5mL of GSK Biologicals' adjuvant AS02A FMP2.1/AS02A: FMP2.1 in GSK Biologicals' AS02A	20 subjects to receive Rabies vaccine (RabAvert). 10 subjects from Cohort 1 and 10 subjects from Cohort 2 Rabies vaccine (RabAvert): RabAvert Rabies vaccine
Measure Participants	20	20	20
Day 0	53295.3 (76881)	56779.4 (53811.2)	59852 (101952.4)
Day 14	62963.8 (77633.3)	120677.4 (104675.9)	63697.6 (119009.9)
Day 30	68251.2 (87406.5)	101464.5 (99045.2)	51436.1 (95888.9)
Day 44	101478.2 (139781.1)	159449.2 (152111.2)	62498.3 (115667.3)
Day 60	103966.8 (117998.7)	187453.9 (162090.9)	77418.1 (147844.9)
Day 74	128323.7 (109759)	227692.0 (236420.5)	82794.3 (173534.6)
Day 90	87684.2 (99596.7)	162739.7 (182897.2)	52575.5 (99568.0)

3. Secondary Outcome

Title	Anti-AMA1 Log Antibody Titers Over Time
Description	Summary of Anti-AMA1 Log Antibody titers on days 0, 14, 30, 44, 60, 74 and 90
Time Frame	90 Days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cohort 1: 25ug FMP2.1 / AS02A	Cohort 2: 50ug FMP2.1 / AS02A	Cohorts 1 and 2: Rabies Vaccine (RabAvert)
Arm/Group Description	20 subject to receive 25ug of FMP2.1 vaccine in 0.25mL of GSK Biologicals' adjuvant AS02A FMP2.1/AS02A: FMP2.1 in GSK Biologicals' AS02A	20 subjects to receive 50ug of FMP2.1 vaccine in 0.5mL of GSK Biologicals' adjuvant AS02A FMP2.1/AS02A: FMP2.1 in GSK Biologicals' AS02A	20 subjects to receive Rabies vaccine (RabAvert). 10 subjects from Cohort 1 and 10 subjects from Cohort 2 Rabies vaccine (RabAvert): RabAvert Rabies vaccine
Measure Participants	20	20	20
Day 0	4.3 (0.7)	44.4 (0.9)	4.2 (0.8)
Day 14	4.5 (0.6)	4.8 (0.6)	4.1 (0.8)
Day 30	4.5 (0.6)	4.7 (0.6)	4.1 (0.8)
Day 44	4.7 (0.5)	5.0 (0.5)	4.1 (0.8)
Day 60	4.8 (0.5)	5.1 (0.5)	4.2 (0.8)
Day 74	4.9 (0.4)	5.2 (0.4)	4.1 (0.8)
Day 90	4.8 (0.4)	5.0 (0.4)	4.0 (0.9)

4. Secondary Outcome

Title	Geometric Mean Antibody Titers Over Time
Description	Measurement of geometric mean antibody titers on days 0, 14, 30, 44, 60, 74 and 90
Time Frame	90 Days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cohort 1: 25ug FMP2.1 / AS02A	Cohort 2: 50ug FMP2.1 / AS02A	Cohorts 1 and 2: Rabies Vaccine (RabAvert)
Arm/Group Description	20 subject to receive 25ug of FMP2.1 vaccine in 0.25mL of GSK Biologicals' adjuvant AS02A FMP2.1/AS02A: FMP2.1 in GSK Biologicals' AS02A	20 subjects to receive 50ug of FMP2.1 vaccine in 0.5mL of GSK Biologicals' adjuvant AS02A FMP2.1/AS02A: FMP2.1 in GSK Biologicals' AS02A	20 subjects to receive Rabies vaccine (RabAvert). 10 subjects from Cohort 1 and 10 subjects from Cohort 2 Rabies vaccine (RabAvert): RabAvert Rabies vaccine
Measure Participants	20	20	20
Day 0	19161.2	23499.7	14354.8
Day 14	30795.3	69751.6	13856.7
Day 30	31804.9	55085.8	12690.7
Day 44	55246.5	100589.6	13941.2
Day 60	61438.6	119191.3	16030.5
Day 74	89856.7	150738.4	14064.5
Day 90	60967.1	102813.0	10425.1

5. Secondary Outcome

Title	Subjects With 2- and 4-fold Increases in Anti-FMP2.1 Antibody Levels Over Time
Description	Proportion of Subjects with 2- and 4-fold increases in Anti-FMP2.1 Antibody levels on days 14, 30, 44, 60, 74 and 90
Time Frame	90 Days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cohort 1: 25ug FMP2.1 / AS02A	Cohort 2: 50ug FMP2.1 / AS02A	Cohorts 1 and 2: Rabies Vaccine (RabAvert)
Arm/Group Description	20 subject to receive 25ug of FMP2.1 vaccine in 0.25mL of GSK Biologicals' adjuvant AS02A FMP2.1/AS02A: FMP2.1 in GSK Biologicals' AS02A	20 subjects to receive 50ug of FMP2.1 vaccine in 0.5mL of GSK Biologicals' adjuvant AS02A FMP2.1/AS02A: FMP2.1 in GSK Biologicals' AS02A	20 subjects to receive Rabies vaccine (RabAvert). 10 subjects from Cohort 1 and 10 subjects from Cohort 2 Rabies vaccine (RabAvert): RabAvert Rabies vaccine
Measure Participants	20	20	20
Day 14 2-fold increase	5 25%	9 45%	0 0%
Day 14 4-fold increase	1 5%	5 25%	0 0%
Day 30 2-fold increase	2 10%	4 20%	0 0%
Day 30 4-fold increase	2 10%	4 20%	0 0%
Day 44 2-fold increase	3 15%	6 30%	0 0%
Day 44 4-fold increase	3 15%	6 30%	0 0%
Day 60 2-fold increase	6 30%	7 35%	0 0%
Day 60 4-fold increase	6 30%	7 35%	0 0%
Day 74 2-fold increase	9 45%	11 55%	0 0%
Day 74 4-fold increase	9 45%	11 55%	0 0%
Day 90 2-fold increase	6 30%	7 35%	0 0%
Day 90 4-fold increase	6 30%	7 35%	0 0%

Adverse Events

Time Frame	12 months
Arm/Group Title	Cohort 1: 25 ug FMP2.1 / AS02		Cohort 2: 50 ug FMP2.1 / AS02A		Cohort 3: Rabies Vaccine (RabAvert)
Arm/Group Description	25 ug FMPs.1 / AS02		50 ug FMP2.1 / AS02A		Rabies vaccine, All events reports instead of AE's per vaccination group 20 subjects (10 from Cohort 1 and 10 from Cohort 2)
All Cause Mortality
	Cohort 1: 25 ug FMP2.1 / AS02		Cohort 2: 50 ug FMP2.1 / AS02A		Cohort 3: Rabies Vaccine (RabAvert)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/20 (0%)		0/20 (0%)
Serious Adverse Events
	Cohort 1: 25 ug FMP2.1 / AS02		Cohort 2: 50 ug FMP2.1 / AS02A		Cohort 3: Rabies Vaccine (RabAvert)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/20 (0%)		0/20 (0%)
Other (Not Including Serious) Adverse Events
	Cohort 1: 25 ug FMP2.1 / AS02		Cohort 2: 50 ug FMP2.1 / AS02A		Cohort 3: Rabies Vaccine (RabAvert)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	20/20 (100%)		20/20 (100%)		20/20 (100%)
Cardiac disorders
Extrasystol	0/20 (0%)	0	0/20 (0%)	0	1/20 (5%)	1
Heart racing	1/20 (5%)	1	0/20 (0%)	0	0/20 (0%)	0
Palpitation	0/20 (0%)	0	1/20 (5%)	1	1/20 (5%)	1
Premature/ectopic heart beat	1/20 (5%)	1	0/20 (0%)	0	0/20 (0%)	0
Tachycardia at 100beats/min	1/20 (5%)	1	3/20 (15%)	3	0/20 (0%)	0
Ear and labyrinth disorders
Left otalgia	1/20 (5%)	1	0/20 (0%)	0	0/20 (0%)	0
Right otitis	2/20 (10%)	2	0/20 (0%)	0	0/20 (0%)	0
Ringing in the ears	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0
Eye disorders
Chalazion	0/20 (0%)	0	2/20 (10%)	2	1/20 (5%)	1
Eye pain	2/20 (10%)	2	1/20 (5%)	1	0/20 (0%)	0
Eye tearing and itching	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0
Keratitis	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0
Ocular affection	0/20 (0%)	0	0/20 (0%)	0	2/20 (10%)	2
Right eye pain	1/20 (5%)	1	0/20 (0%)	0	0/20 (0%)	0
Right eye pterygium	1/20 (5%)	1	0/20 (0%)	0	0/20 (0%)	0
Visual floaters	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0
Gastrointestinal disorders
Abdominal pain	2/20 (10%)	2	4/20 (20%)	4	1/20 (5%)	1
Bilious vomiting	1/20 (5%)	1	0/20 (0%)	0	0/20 (0%)	0
Blood streak in stool	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0
Dental cavity tooth #18	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0
Diarrhea	0/20 (0%)	0	0/20 (0%)	0	3/20 (15%)	3
Dysentery	1/20 (5%)	1	0/20 (0%)	0	0/20 (0%)	0
Dyspepsia	2/20 (10%)	2	0/20 (0%)	0	0/20 (0%)	0
Epigastric pain	2/20 (10%)	2	2/20 (10%)	2	0/20 (0%)	0
Eructation	0/20 (0%)	0	0/20 (0%)	0	2/20 (10%)	2
Gastritis	0/20 (0%)	0	1/20 (5%)	1	2/20 (10%)	2
Gingivitis	1/20 (5%)	1	0/20 (0%)	0	0/20 (0%)	0
Heartburn	1/20 (5%)	1	0/20 (0%)	0	0/20 (0%)	0
Hypochondrium pain	0/20 (0%)	0	0/20 (0%)	0	1/20 (5%)	1
Left upper premolar tooth pain	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0
Liquid diarrhea	1/20 (5%)	1	2/20 (10%)	2	0/20 (0%)	0
Nausea	5/20 (25%)	5	2/20 (10%)	2	0/20 (0%)	0
Pain in right hypochondium	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0
Pain of right hypochondrium	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0
Pain with shaking of the right hypochondrium	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0
Presence of blood in stools	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0
Right inguinal hernia	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0
Toothache	0/20 (0%)	0	0/20 (0%)	0	2/20 (10%)	2
Vomiting	0/20 (0%)	0	1/20 (5%)	1	1/20 (5%)	1
General disorders
Excessive sweating	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0
Facial sweating	1/20 (5%)	1	0/20 (0%)	0	0/20 (0%)	0
Fatigue	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0
Febrile at 37.5 C	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0
Febrile to 37.8 C	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0
Fever	6/20 (30%)	6	4/20 (20%)	4	0/20 (0%)	0
Flu like symptoms	11/20 (55%)	11	8/20 (40%)	8	0/20 (0%)	0
Malaise	6/20 (30%)	6	7/20 (35%)	7	0/20 (0%)	0
Physical weakness	2/20 (10%)	2	3/20 (15%)	3	0/20 (0%)	0
Subjective evening fever	2/20 (10%)	2	2/20 (10%)	2	0/20 (0%)	0
Sweats	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0
Swelling of right thumb	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0
Temperature = 37.5C	1/20 (5%)	1	0/20 (0%)	0	0/20 (0%)	0
Thumb inflammation	0/20 (0%)	0	0/20 (0%)	0	1/20 (5%)	1
Immune system disorders
Allergic cold symptoms	1/20 (5%)	1	0/20 (0%)	0	0/20 (0%)	0
Allergic conjunctivitis	1/20 (5%)	1	0/20 (0%)	0	0/20 (0%)	0
Hives	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0
Infections and infestations
Bacterial conjunctivitis	1/20 (5%)	1	0/20 (0%)	0	0/20 (0%)	0
Conjunctivitis	0/20 (0%)	0	1/20 (5%)	1	2/20 (10%)	2
Dental abscess tooth #21	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0
Dermatomycosis of inguinal folds	1/20 (5%)	1	0/20 (0%)	0	0/20 (0%)	0
Epididymitis	0/20 (0%)	0	1/20 (5%)	1	1/20 (5%)	1
Conjunctivitis left eye	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0
Periodontitis	1/20 (5%)	1	0/20 (0%)	0	0/20 (0%)	0
Pityriasis versicolor	1/20 (5%)	1	1/20 (5%)	1	0/20 (0%)	0
Purulent conjunctivitis	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0
Right eye conjunctivitis	1/20 (5%)	1	0/20 (0%)	0	0/20 (0%)	0
Super infected wounds on left leg	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0
Syndrome of tissue hyperfusion	1/20 (5%)	1	0/20 (0%)	0	0/20 (0%)	0
Syndrome typhic	0/20 (0%)	0	0/20 (0%)	0	2/20 (10%)	2
Typhoid syndrome	1/20 (5%)	1	1/20 (5%)	1	0/20 (0%)	0
Uncomplicated malaria episode	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0
Injury, poisoning and procedural complications
Acute injection site pain	2/20 (10%)	2	3/20 (15%)	3	0/20 (0%)	0
Foreign body in eye causing tearing	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0
Induced injection site pain	1/20 (5%)	1	0/20 (0%)	0	0/20 (0%)	0
Injection site edema (grade 1)	4/20 (20%)	4	2/20 (10%)	2	0/20 (0%)	0
Injection site edema (grade 2	20/20 (100%)	20	9/20 (45%)	9	0/20 (0%)	0
Injection site edema (grade 3)	9/20 (45%)	9	20/20 (100%)	20	0/20 (0%)	0
Injection site pain (grade 1)	20/20 (100%)	20	20/20 (100%)	20	1/20 (5%)	1
Injection site pain (grade 2)	1/20 (5%)	1	3/20 (15%)	3	0/20 (0%)	0
Injection site pain with pulsatile sensation (grade 1)	1/20 (5%)	1	0/20 (0%)	0	0/20 (0%)	0
Injection site pain extending to left elbow (grade 1)	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0
Injection site pain extending to left shoulder (grade 1)	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0
Injection site pain with movement (grade 1)	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0
Injection site pruritus	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0
Injection site pulsation (grade 1)	1/20 (5%)	1	0/20 (0%)	0	0/20 (0%)	0
Injury	0/20 (0%)	0	0/20 (0%)	0	8/20 (40%)	8
Left food punture wound	1/20 (5%)	1	0/20 (0%)	0	0/20 (0%)	0
Left foot scratch	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0
Left foot wound on lateral, external aspect	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0
Needle stick injury	1/20 (5%)	1	0/20 (0%)	0	0/20 (0%)	0
Pain at venipuncture site	1/20 (5%)	1	1/20 (5%)	1	0/20 (0%)	0
Post-traumatic pain of the right elbow and wrist	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0
Post-traumatic right foot pain	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0
Right ankle pain after dislocation since 2002	1/20 (5%)	1	0/20 (0%)	0	0/20 (0%)	0
Right ankle traumatic wound	1/20 (5%)	1	0/20 (0%)	0	0/20 (0%)	0
Right index finger traumatic wound	1/20 (5%)	1	0/20 (0%)	0	0/20 (0%)	0
Right leg traumatic wound	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0
Right wrist scratch on posterior aspect	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0
Scratch	1/20 (5%)	1	2/20 (10%)	2	3/20 (15%)	3
Scratch of anterior/external aspect of the thigh	1/20 (5%)	1	0/20 (0%)	0	0/20 (0%)	0
Sense of pulsation at injection site	1/20 (5%)	1	0/20 (0%)	0	0/20 (0%)	0
Traumatic leg wound	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0
Traumatic pain of left toes	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0
Traumatic wound of right ring fingure	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0
Traumatic wound of the middle finger	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0
Traumatic wound of the right knee	1/20 (5%)	1	0/20 (0%)	0	0/20 (0%)	0
Wound	0/20 (0%)	0	0/20 (0%)	0	4/20 (20%)	4
Investigations
Elevated temperature	0/20 (0%)	0	0/20 (0%)	0	2/20 (10%)	2
Metabolism and nutrition disorders
Anorxia	1/20 (5%)	1	0/20 (0%)	0	1/20 (5%)	1
Edema of left anterior forearm	1/20 (5%)	1	0/20 (0%)	0	0/20 (0%)	0
Post-traumatic edema of forehead	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0
Musculoskeletal and connective tissue disorders
Acute lower back pain	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0
Acute left inferior deltoid pain	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0
Arthralgia	0/20 (0%)	0	1/20 (5%)	1	2/20 (10%)	2
Burning muscular pain	1/20 (5%)	1	0/20 (0%)	0	0/20 (0%)	0
Chills	6/20 (30%)	6	3/20 (15%)	3	1/20 (5%)	1
Coxalgy	0/20 (0%)	0	0/20 (0%)	0	1/20 (5%)	1
Hip pain	0/20 (0%)	0	2/20 (10%)	2	0/20 (0%)	0
Joint pain	2/20 (10%)	2	1/20 (5%)	1	0/20 (0%)	0
Limitation of arm movement	5/20 (25%)	5	3/20 (15%)	3	0/20 (0%)	0
Lombalgia	0/20 (0%)	0	0/20 (0%)	0	4/20 (20%)	4
Lower back pain	2/20 (10%)	2	2/20 (10%)	2	0/20 (0%)	0
Mucsle aches	1/20 (5%)	1	1/20 (5%)	1	0/20 (0%)	0
Muscle pain of abdominal muscles and at venipuncture site	1/20 (5%)	1	0/20 (0%)	0	0/20 (0%)	0
Muscular pain of right lower extremity following trauma	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0
Myalgia	5/20 (25%)	5	11/20 (55%)	11	4/20 (20%)	4
Pain in anterior left forearm	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0
Pain of right knee	1/20 (5%)	1	0/20 (0%)	0	0/20 (0%)	0
Pulled groin muscle	2/20 (10%)	2	0/20 (0%)	0	0/20 (0%)	0
Right lumbar pain	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0
Sensation of arm heaviness	1/20 (5%)	1	0/20 (0%)	0	0/20 (0%)	0
Sensation of head heaviness	0/20 (0%)	0	3/20 (15%)	3	0/20 (0%)	0
Nervous system disorders
Diffuse headache	0/20 (0%)	0	2/20 (10%)	2	0/20 (0%)	0
Dizziness	0/20 (0%)	0	0/20 (0%)	0	2/20 (10%)	2
Evening headache	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0
Frontal headache	1/20 (5%)	1	1/20 (5%)	1	0/20 (0%)	0
Headache	20/20 (100%)	20	17/20 (85%)	17	5/20 (25%)	5
Headache in frontal region	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0
Headache in temporal region	1/20 (5%)	1	3/20 (15%)	3	0/20 (0%)	0
Headaches	3/20 (15%)	3	7/20 (35%)	7	5/20 (25%)	5
Loss of balance with movement	1/20 (5%)	1	0/20 (0%)	0	0/20 (0%)	0
Migraine	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0
Paroxysmal vertigo	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0
Torticollis	1/20 (5%)	1	1/20 (5%)	1	1/20 (5%)	1
Transient loss of balance	1/20 (5%)	1	1/20 (5%)	1	0/20 (0%)	0
Vertigo	2/20 (10%)	2	1/20 (5%)	1	0/20 (0%)	0
Psychiatric disorders
Insomnia	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0
Renal and urinary disorders
Burning with urination	1/20 (5%)	1	1/20 (5%)	1	0/20 (0%)	0
Pain with urination	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0
Urethral discharge	0/20 (0%)	0	2/20 (10%)	2	0/20 (0%)	0
Urinary tract infection	0/20 (0%)	0	1/20 (5%)	1	5/20 (25%)	5
Reproductive system and breast disorders
Dysmenorrhea	1/20 (5%)	1	0/20 (0%)	0	0/20 (0%)	0
Left pelvic pain	1/20 (5%)	1	0/20 (0%)	0	0/20 (0%)	0
Positive urine pregnancy test	1/20 (5%)	1	0/20 (0%)	0	0/20 (0%)	0
Vulvitis	1/20 (5%)	1	0/20 (0%)	0	0/20 (0%)	0
Whitish leukorrhea	1/20 (5%)	1	0/20 (0%)	0	0/20 (0%)	0
Respiratory, thoracic and mediastinal disorders
Acute pharyngitis	1/20 (5%)	1	0/20 (0%)	0	0/20 (0%)	0
Acute rhinitis	3/20 (15%)	3	0/20 (0%)	0	0/20 (0%)	0
Acute sinusitis	1/20 (5%)	1	0/20 (0%)	0	0/20 (0%)	0
Acute viral rhinitis	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0
Cold	0/20 (0%)	0	0/20 (0%)	0	7/20 (35%)	7
Cold symptoms	13/20 (65%)	13	5/20 (25%)	5	0/20 (0%)	0
Cold symptoms with productive cough	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0
Cough	1/20 (5%)	1	0/20 (0%)	0	3/20 (15%)	3
Dry cough	8/20 (40%)	8	1/20 (5%)	1	0/20 (0%)	0
Flu	0/20 (0%)	0	0/20 (0%)	0	3/20 (15%)	3
Frontal sinusitis	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0
Left rhinitis	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0
Nighttime cough	1/20 (5%)	1	0/20 (0%)	0	0/20 (0%)	0
Nighttime wet cough triggered by cigarette smoke	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0
Oropharyngitis	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0
Productive cough	0/20 (0%)	0	2/20 (10%)	2	0/20 (0%)	0
Rhinitis	8/20 (40%)	8	9/20 (45%)	9	0/20 (0%)	0
Rhinitis of mucous membranes	1/20 (5%)	1	0/20 (0%)	0	0/20 (0%)	0
Rhinobronchitis	2/20 (10%)	2	3/20 (15%)	3	2/20 (10%)	2
Rhinopharyngitis	0/20 (0%)	0	2/20 (10%)	2	1/20 (5%)	1
Rhinosinusitis	1/20 (5%)	1	0/20 (0%)	0	0/20 (0%)	0
Right tonsillitis	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0
Sinisitis + Rhinitis	1/20 (5%)	1	0/20 (0%)	0	0/20 (0%)	0
Sinusitis	1/20 (5%)	1	0/20 (0%)	0	0/20 (0%)	0
Tonsillitis	4/20 (20%)	4	1/20 (5%)	1	1/20 (5%)	1
Viral rhinopharyngitis	1/20 (5%)	1	0/20 (0%)	0	0/20 (0%)	0
Skin and subcutaneous tissue disorders
Abrasion from scratching	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0
Bilateral ocular pruritus	1/20 (5%)	1	0/20 (0%)	0	0/20 (0%)	0
Bilateral pruritus of forearms	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0
Boil	0/20 (0%)	0	0/20 (0%)	0	1/20 (5%)	1
Bullous pruritic lesions of upper extremities	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0
Erythema extending from injection site	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0
Furuncle	1/20 (5%)	1	1/20 (5%)	1	0/20 (0%)	0
Generalized pruritus and skin papules	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0
Isolated pruritus of the umbilical region	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0
Non-pruritic papule	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0
Papule of the posterior ankle and inferior left abdominal flank	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0
Papule on mid-flank of right abdomen	1/20 (5%)	1	0/20 (0%)	0	0/20 (0%)	0
Papule pruritus	0/20 (0%)	0	0/20 (0%)	0	3/20 (15%)	3
Papule unpruritus	0/20 (0%)	0	0/20 (0%)	0	1/20 (5%)	1
Papules + pruritus following an insect bite	1/20 (5%)	1	0/20 (0%)	0	0/20 (0%)	0
Pruritic papules	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0
Pruritus	1/20 (5%)	1	0/20 (0%)	0	1/20 (5%)	1
Pruritis of internal face of thighs	1/20 (5%)	1	0/20 (0%)	0	0/20 (0%)	0
Pruritis papule	1/20 (5%)	1	0/20 (0%)	0	0/20 (0%)	0
Pruritis with papules and excoriation	1/20 (5%)	1	0/20 (0%)	0	0/20 (0%)	0
Pruritis with skin abrasions from scratching	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0
Surgical and medical procedures
Dental extraction	1/20 (5%)	1	0/20 (0%)	0	0/20 (0%)	0
Groin elongation	0/20 (0%)	0	0/20 (0%)	0	2/20 (10%)	2
Gum pain following tooth extraction	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0
Painful dental cavity (tooth extraction)	1/20 (5%)	1	0/20 (0%)	0	0/20 (0%)	0
post-operative pain at wound site	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0
Surgical hernia repair	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0
Vascular disorders
Elevated blood pressure = 150/90 mmHg	1/20 (5%)	1	0/20 (0%)	0	0/20 (0%)	0
Epistaxis	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0
Hemorrhoids	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0
Orthostatic hypotension	1/20 (5%)	1	0/20 (0%)	0	0/20 (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.