Safety and long-term immunological effects of CryJ2-LAMP plasmid vaccine in Japanese red cedar atopic subjects: A phase I study

Figures & data

Figure 1. Study Design for the CryJ2-LAMP trial. Route of Administration – intramuscular (IM); * Average of days from the visit #2 to the #8; ** Average 166 d from the visit #8 to the visit #9.

Table 1. Demographics and Baseline Characteristics.

Demographics Variable	Category	Cohort 1 (n=6)	Cohort 2 (n=9)	Cohort 3 (n=9)	Overall (n=24)
Gender	Male	3	3	3	9
	Female	3	6	6	15
Race	Asian	6	9	9	24
Residency Status	Japanese Born Permanent US Resident	4	5	2	11
	Japanese Born Temporary US Resident	1	3	7	11
	US Born Lived in Japan		1		1
	Japanese Born U.S. Citizen	1			1
Age (years)	Mean (Std Dev)	41.5 (7.56)	46.33 (7.58)	36.22 (6.46)	41.33 (8.18)
	Min	32	35	24	24
	Max	53	61	44	61
	Median	42	44	37	41
Heights (cm^a)	Mean (Std Dev)	168.40 (12.20)	173.28 (10.67)	161.72 (8.43)	162.67 (10.44)
	Min	150	145	150	145
	Max	180	180	175	180
	Median	169	158	163	163
Weights (Kg)	Mean (Std Dev)	69.08 (14.73)	59.97 (13.15)	62.75 (13.06)	63.29 (13.41)
	Min	49.4	46.7	39.9	39.9
	Max	91.2	90.7	74.4	91.2
	Median	66.7	56.7	68.5	69.4
FEV1 predicted (%)*	Mean (Std Dev)	92.80 (15.37)	91.78 (11.04)	89.44 (9.37)	91.17 (11.35)
	Min	74	77	76	74
	Max	115	107	107	115
	Median	87	94	91	90.5

•FEV1 predicted (%): FEV1% (Forced expiratory volume in 1 second) of the subject divided by the average FEV1% in the population for any person of similar age, sex and body composition.

^aHeights/Weights were originally measured by using imperial system and converted into metric system for consistency.

Table 2. Summary of all TEAEs by Cohort (day 0 - day 132).

	# AEs		# AEs	# AEs	# AEs
	Overall		Cohort 1	Cohort 2	Cohort 3
AE Description	N=24	% AEs	N=6	N=9	N=9	Severity	Causality
Hyperpigmented Papule at injection site	1	1%			1	Mild	Definitely Related
Itching at Injection Site	1	1%			1	Mild	Definitely Related
Pain at Injection Site	3	3%			3	Mild	Definitely Related
Pruritis at Injection Site	2	2%			2	Mild	Definitely Related
Redness at Injection Site	24	27%	7	2	15	Mild	Definitely Related
Swelling at Injection Site	10	11%	5		5	Mild	Definitely Related
Fatigue	13	15%		2	11	Mild	Possibly Related
Fatigue	1	1%	1			Moderate	Possibly Related
Headache	12	14%	3	1	8	Mild	Possibly Related
Loss of Appetite	1	1%		1		Mild	Possibly Related
Muscle Aches, Generalized	1	1%			1	Mild	Possibly Related
Cervical Radiculopathy	1	1%		1		Moderate	Definitely Not Related
Dental Caries	1	1%		1		Moderate	Definitely Not Related
Elevated Blood Pressure	1	1%		1		Moderate	Definitely Not Related
Flea Bites	1	1%		1		Moderate	Definitely Not Related
Headache	1	1%			1	Moderate	Definitely Not Related
Influenza	1	1%		1		Moderate	Definitely Not Related
Insect bite	1	1%	1			Mild	Definitely Not Related
Numbness in Hard Palate	1	1%			1	Mild	Definitely Not Related
Pain in Right Forearm (not at inject site)	1	1%		1		Moderate	Definitely Not Related
Shingles	1	1%			1	Moderate	Definitely Not Related
Upper Respiratory Infection	2	2%			2	Mild	Definitely Not Related
Upper Respiratory Infection	1	1%	1			Moderate	Definitely Not Related
Abdominal Pain	1	1%	1			Moderate	Probably Not Related
Body Aches, Generalized	1	1%	1			Moderate	Probably Not Related
Bruise at Injection Site	1	1%			1	Mild	Probably Not Related
Dizziness	1	1%	1			Mild	Probably Not Related
Headache	1	1%		1		Mild	Probably Not Related
Pruritus in Ears	1	1%			1	Mild	Probably Not Related
TOTAL	88		21	13	54

^a Adverse events coded using MedDRA Version 15.0.

^b A treatment emergent adverse event is an adverse event that occurs after the subject receives any dose of the assigned study treatment.

^c Two of the 88 AEs occurred during the extension period, 72 days through 132 days.

Table 3. Summary of all AEs during the Phase IB Trial.

			Cohort #
AE Description	# AEs	% AEs	Subject ID	Severity	Causality
Delayed Hypersensitivity to Histamine Control Solution at ID Injection Site	1	11%	Cohort 2	Moderate	Definitely Not Related
Delayed Hypersensitivity to Southern Grass Mix at ID Injection Site	1	11%		Moderate	Definitely Not Related
			Subject #120
Itchiness at Intradermal Injection Sites (for S. Grass Mix & Histamine) ID test	1	11%		Moderate	Definitely Not Related
Itchiness at Vaccine Injection Site	1	11%	Cohort 3	Mild	Definitely Related
			Subject #125
Fatigue	1	11%	Cohort 3	Mild	Possibly Related
Ecchymosis, Left Thigh	1	11%		Mild	Definitely Not Related
Ecchymosis, Left Upper Arm (Not at the injection site)	1	11%	Subject #121	Mild	Definitely Not Related
Ecchymosis, Right Thigh	1	11%		Mild	Definitely Not Related
Headache	1	11%		Moderate	Definitely Not Related
TOTAL	9

^a Adverse events coded using MedDRA Version 15.0.

^b A treatment emergent adverse event is an adverse event that occurs after the subject receives any dose of the assigned study treatment.

Table 4. Skin Prick Test Results for JRC and MC.

		Phase IA		Phase IA		Phase IB		Phase IB		Phase IB
Group	Subject ID	Japanese Cedar	Mountain Cedar	Japanese Cedar	Mountain Cedar	Japanese Cedar	Mountain Cedar	Japanese Cedar	Mountain Cedar	Japanese Cedar	Mountain Cedar
		Visit #1 Screen		Visit #8 (Day 132^*)		Visit #9 (Days 284–321)		Visit #11 (Days 335–377)		Visit #12 (Days 361–398)
Cohort 1 4 mg/dose	101	Negative	Negative	Negative	Negative	—	—	—	—	—	—
	108	Negative	Negative	Negative	Negative	Negative	Negative	Negative	Negative	Negative	Negative
	111	Negative	Negative	Negative	Negative	—	—	—	—	—	—
	114	Negative	Negative	Negative	Negative	Negative	Negative	Negative	Negative	Negative	Negative
	115	Negative	Negative	Negative	Negative	Negative	Negative	Negative	Negative	Negative	Negative
	119	Negative	Negative	Negative	Negative	Negative	Negative	Negative	Negative	Negative	Negative
		Visit #1 Screen		Visit #8 (Day 132^*)		Visit #9 (Days 273–337)		Visit #11 (Days 327–386)		Visit #12 (Days 355–416)
Cohort 2 2mg/dose	102	Positive	Negative	Negative	Negative	Negative	Negative	Negative	Negative	Negative	Negative
	103	Positive	Positive	Negative	Negative	Negative	Negative	Negative	Negative	Negative	Negative
	107	Negative	Positive	Negative	Negative	Negative	Negative	Negative	Negative	Negative	Negative
	109	Positive	Negative	Negative	Negative	Negative	Negative	Negative	Negative	Negative	Negative
	118	Negative	Positive	Negative	Positive	Negative	Negative	Negative	Positive	Positive	Positive
	120	Negative	Positive	Negative	Negative	Negative	Negative	^**	^**	ET	ET
	123	Positive	Negative	Negative	Negative	Negative	Negative	Negative	Negative	Negative	Negative
	126	Positive	Positive	Negative	Negative	—	—	—	—	—	—
	137	Positive	Positive	Moved	Moved	Moved	Moved	Moved	Moved	Moved	Moved
		Visit #1 Screen		Visit #8 (Day 132^*)		Visit #9 (Days 252–316)		Visit #11 (Days 303–376)		Visit #12 (Days 331–398)
Cohort 3 4mg/dose	105	Positive	Positive	Positive	Positive	—	—	—	—	—	—
	106	Positive	Negative	Negative	Negative	Negative	Negative	Negative	Negative	Negative	Negative
	112	Positive	Positive	Negative	Positive	Negative	Negative	Negative	Negative	Negative	Negative
	121	Positive	Negative	Negative	Negative	Negative	Negative	Negative	Negative	Negative	Negative
	122	Positive	Positive	Negative	Negative	Negative	Negative	Negative	Negative	Negative	Negative
	125	Negative	Positive	Negative	Negative	Negative	Negative	Negative	Negative	Negative	Negative
	132	Positive	Negative	Positive	Negative	—	—	—	—	—	—
	136	Positive	Positive	Negative	Positive	—	—	—	—	—	—
	140	Negative	Positive	Positive	Positive	Negative	Negative	Negative	Negative	Negative	Negative

— did not participate

^ˆˆ Visit 10 Booster Administration

** Visit skipped 166 Days- Average of days between Phase IA visit #8 and Phase IB visit #9 for all subjects ET Early termination

* Average of days from the visit #2 (First Vaccination) to the visit #8

Bold: conversion from negative to positive

Italics: conversion from positive to negative

Table 5. Skin Prick Test Results for Allergens Unrelated to JRC and MC.

Cohort 1						Cohort 2						Cohort 3
Non-allergic subjects 4mg/dose						Allergic subjects 2mg/dose						Allergic subjects 4mg/ml
ID	Day	S. Grass	W. Rag.	S. Calif tree	Dust Mite	ID	Day	S. Grass	W. Rag.	S. Calif tree	Dust Mite	ID	Day	S. Grass	W. Rag.	S. Calif tree	Dust Mite
108	0	—	—	+	+	102	0	—	+	—	+	106	0	—	+	+	—
	132	—	—	+	+		132	—	—	—	+		132	—	—	—	—
	298^a	—	—	+	—		298	—	—	—	+		298	—	—	—	—
	350^b	—	—	—	—		350	—	—	—	+		350	—	—	—	—
	380^c	—	—	—	—		380	—	—	—	+		380	—	—	—	—
114	0	—	—	—	—	103	0	+	—	—	—	112	0	+	—	—	+
	132	—	—	—	—		132	+	—	—	—		132	+	—	—	—
	298	—	—	—	+		298	+	—	—	—		298	—	—	—	—
	350	—	—	—	—		350	—	—	—	—		350	—	—	—	+
	380	—	—	—	—		380	+	—	—	—		380	+	—	—	—
115	0	—	—	—	—	107	0	—	—	—	+	121	0	—	—	—	+
	132	+	—	—	—		132	—	—	—	+		132	—	—	—	—
	298	+	—	—	—		298	—	—	—	+		298	—	—	—	—
	350	—	—	—	—		350	—	—	—	+		350	—	—	—	—
	380	+	—	—	—		380	—	—	—	+		380	—	—	—	—
119	0	—	—	—	—	109	0	—	—	+	+	122	0	+	—	—	—
	132	—	—	—	—		132	—	—	+	+		132	—	—	—	—
	298	—	—	—	—		298	—	—	+	+		298	—	—	—	—
	350	—	—	—	—		350	—	—	+	+		350	—	—	—	—
	380	—	—	—	—		380	—	—	+	+		380	—	—	—	—
101	0	—	—	—	—	118	0	—	—	+	—	125	0	—	—	—	—
	132	—	—	—	—		132	+	—	—	—		132	—	—	—	—
111	0	—	—	—	—		298	—	—	—	—		298	—	—	+	+
	132	—	—	—	—		350	—	—	—	—		350	—	—	+	+
							380	—	—	—	—		380	—	—	+	+
						120	0	+	—	—	+	140	0	+	+	—	+
							132	—	—	—	+		132	+	—	—	—
							298	—	—	—	+		298	+	—	—	+
							350	^**	^**	^**	^**		350	+	—	—	+
							380	ET	ET	ET	ET		380	+	—	—	+
						123	0	+	—	—	+	105	0	—	—	—	+
							132	—	—	—	—		132	—	+	—	+
							298	—	—	—	+	132	0	—	—	—	—
							350	—	—	—	+		132	+	—	—	—
							380	—	—	—	+	136	0	—	—	—	+
						126	0	+	—	+	+		132	—	—	—	+
							132	—	—	+	+

** Visit skipped ET Early termination

^a Average days from the Phase IA visit #2 (day 0) to the Phase IB visit #9 for all subjects in a range of 252–337 days

^b Average days from day 0 to the Phase IB visit #11 for all subjects in a range of 303–386 days

^c Average days from day 0 to the Phase IB visit #12 for all subjects in a range of 331–416 days

^d Bold: conversion from negative to positive

^e Italics: conversion from positive to negative