Phase III Cat-PAD Study

A Double-Blind, Randomised, Placebo-Controlled Multi-Centre Field Study to Assess the Efficacy and Safety of Cat-PAD Peptide Immunotherapy in Cat Allergic Subjects

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01620762

Enrollment

1408

Registered

2012-06-15

Start date

2012-10-31

Completion date

Unknown

Last updated

2018-06-15

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Rhinoconjunctivitis

Keywords

Cat allergy, Rhinoconjunctivitis

Brief summary

The purpose of this study is to compare the treatment effect of two treatment regimens of Cat-PAD vs placebo and to evaluates the treatment effect of Cat-PAD on symptoms, rescue medication usage and Quality of Life.

Interventions

DRUGPlacebo

1 dose every 4 weeks

DRUGCat-PAD

1 dose every 4 weeks

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

12 Years to 65 Years

Healthy volunteers

Inclusion criteria

* Male or female, aged 12-65 years. * Moderate to severe rhinoconjunctivitis on exposure to cats for at least 2 years. * Subjects may optionally also have GINA Step 1 controlled asthma. * Positive skin prick test to cat hair. * Cat dander specific IgE ≥0.35 kU/L.

Exclusion criteria

* Asthma falling under the GINA definitions partly controlled and uncontrolled or Steps 2 to 5. * FEV1 \<80% of predicted. * Clinically significant confounding symptoms of allergy to seasonal allergens during the final evaluation period. * Skin prick test 5 mm greater than the negative control to perennial allergens or animal dander (other than cat) which cannot be avoided during the study. * Significant symptoms of another clinically relevant illness that is likely to affect scoring of rhinoconjunctivitis symptoms. * Clinically relevant abnormalities detected on physical examination. * History of severe drug allergy, severe angioedema or anaphylactic reaction to food.

Design outcomes

Primary

Measure	Time frame	Description
Mean Combined Score in Cat-PAD Treatment Groups Compared With Placebo	52-54 weeks after randomisation	The primary endpoint was the mean Combined Score (CS) measured over a 3 week period (52-54 weeks after randomisation) in the Cat-PAD treatment groups compared with the mean CS in the placebo group. A higher score indicated worse symptoms or greater use of medication and thus a low score indicated a better outcome. CS = Total Rhinoconjunctivitis Symptom Score (TRSS) + Rescue Medication Score (RMS). Eight symptoms are defined in the TRSS, 4 nasal symptoms: runny nose, sneezing; blocked nose, and itchy nose and 4 ocular symptoms: itchy eyes; watery eyes; red eyes and sore eyes. Each symptom was rated in severity on a score of 0-3 (0=absent, 3=severe) and the total was divided by the number of symptoms to provide an average score per symptom of 0-3. RMS was scored from 0 (no allergy rescue medication use per day) to 3 (at least one dose of systemic corticosteroid per day). The RMS score was not additive, and therefore the maximum RMS was 3 and the maximum CS was 6.

Secondary

Measure	Time frame	Description
Mean Daily TOSS in Cat-PAD Compared to Placebo	52-54 weeks after randomisation	Mean daily Total Ocular Symptom Score (TOSS) in Cat-PAD treatment groups compared to placebo groups TOSS was the sum of all the ocular symptom scores (itchy eyes; watery eyes; red eyes; sore eyes) and could range from 0 to 12. Higher TOSS reflected more severe symptoms. Subjects rated the severity of each symptom over the last 24 hours as follows: 0. absent; 1. mild, barely noticeable; 2. moderate, annoying/troublesome; 3. severe, very annoying/very troublesome. Symptoms were scored daily for a period of approximately 3 weeks. 52-54 weeks after randomisation.
Mean TRSS	52-54 weeks after randomisation	Mean Total Rhinoconjunctivitis Symptom Score (TRSS) in Cat-PAD treatment groups compared with placebo. Eight symptoms are defined in the TRSS, 4 nasal symptoms: runny nose, sneezing; blocked nose, and itchy nose and 4 ocular symptoms: itchy eyes; watery eyes; red eyes, and sore eyes. Each symptom was rated in severity on a score of 0-3 (0. absent; 1. mild, barely noticeable; 2. moderate, annoying/troublesome; 3. severe, very annoying/very troublesome), therefore TRSS could range from 0 to 24. Higher TRSS reflected more severe symptom scores. Symptoms were scored daily for a period of approximately 3 weeks. 52-54 weeks after randomisation.
Mean Daily TNSS in Cat-PAD Compared With Placebo	52-54 weeks after randomisation	TNSS (Total nasal symptom score) was the sum of all the nasal symptom scores (runny nose; sneezing; blocked nose; itchy nose) and could range from 0 to 12. Higher TNSS reflected more severe symptoms. Subjects rated the severity of each symptom over the last 24 hours as follows: 0. absent; 1. mild, barely noticeable; 2. moderate, annoying/troublesome; 3. severe, very annoying/very troublesome. Symptoms were scored daily for a period of approximately 3 weeks. 52-54 weeks after randomisation.
Mean RQLQ Score in Cat-PAD Compared With Placebo	52-54 weeks after randomisation	The RQLQ (Rhinoconjunctivitis Quality of Life Questionnaire) was completed by subjects at the end of the study (52-54 weeks after randomisation). The RQLQ is a validated method of assessing quality of life and has 28 questions in seven domains (activity limitation, sleep problems, nasal symptoms, eye symptoms, non-nasal/eye symptoms, practical problems and emotional function). Subjects recalled how their rhinoconjunctivitis had been during the last week and responded to each question on a seven-point scale (0 = no impairment, 6 = maximum impairment). The questions were equally weighted, and the RQLQ score was the mean of the 28 questions and could range from zero to six.
Number of Days With no Moderate or Severe TRSS Symptoms Without Rescue Medication Use	52-54 week after randomisaiton	The number of well days, i.e., days with no moderately or severely annoying symptoms and with no rescue medication used was calculated for all subjects over a period of approximately 21 days, 52-54 weeks after randomisation.
Mean RMS in Cat-PAD Compared With Placebo	52-54 weeks after randomisation	Mean RMS (Rescue medication score) in Cat-PAD treatment groups compared with placebo groups. The use of rhinoconjunctivitis rescue medications was recorded by the subject on a daily basis just before bedtime for approximately 21 days, 52-54 weeks after randomisation and was scored based on a previously published system as follows: 0 = no allergy rescue medication used per day; 0.5 = at least one dose of antihistamine eye drops used per day; 1 = at least one dose of oral antihistamine used per day; 2 = at least one dose of intranasal corticosteroid used per day; 3 = at least one dose of systemic corticosteroid used per day. The score was according to the highest level of rescue medication used and was not additive.

Countries

Belgium, Canada, Czechia, Germany, Hungary, Poland, Russia, Slovakia, United States

Participant flow

Participants by arm

Arm	Count
Cat-PAD Treatment 1 (1 Course) Cat-PAD Treatment 1 Cat-PAD: 1 dose every 4 weeks Placebo: 1 dose every 4 weeks	468
Cat-PAD Treatment 2 (2 Courses) Cat-PAD Treatment regimen 2 Cat-PAD: 1 dose every 4 weeks	470
Placebo Placebo Placebo: 1 dose every 4 weeks	470
Total	1,408

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Overall Study	Adverse Event	9	5	2
Overall Study	Lost to Follow-up	11	17	10
Overall Study	Non-specified	3	6	5
Overall Study	Protocol deviation	1	1	6
Overall Study	Protocol Violation	1	1	1
Overall Study	Subject deterioration	0	1	1
Overall Study	Use of prohibted therapies	0	1	1
Overall Study	Withdrawal by Subject	23	26	27

Baseline characteristics

Characteristic	Cat-PAD Treatment 1 (1 Course)	Cat-PAD Treatment 2 (2 Courses)	Placebo	Total
Age, Categorical <=18 years	29 Participants	29 Participants	32 Participants	90 Participants
Age, Categorical >=65 years	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical Between 18 and 65 years	439 Participants	441 Participants	438 Participants	1318 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	8 Participants	1 Participants	2 Participants	11 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	458 Participants	468 Participants	463 Participants	1389 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants	1 Participants	5 Participants	8 Participants
Sex: Female, Male Female	301 Participants	317 Participants	317 Participants	935 Participants
Sex: Female, Male Male	167 Participants	153 Participants	153 Participants	473 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —
other Total, other adverse events	298 / 467	299 / 470	305 / 470
serious Total, serious adverse events	11 / 467	13 / 470	9 / 470

Outcome results

Primary

Mean Combined Score in Cat-PAD Treatment Groups Compared With Placebo

The primary endpoint was the mean Combined Score (CS) measured over a 3 week period (52-54 weeks after randomisation) in the Cat-PAD treatment groups compared with the mean CS in the placebo group. A higher score indicated worse symptoms or greater use of medication and thus a low score indicated a better outcome. CS = Total Rhinoconjunctivitis Symptom Score (TRSS) + Rescue Medication Score (RMS). Eight symptoms are defined in the TRSS, 4 nasal symptoms: runny nose, sneezing; blocked nose, and itchy nose and 4 ocular symptoms: itchy eyes; watery eyes; red eyes and sore eyes. Each symptom was rated in severity on a score of 0-3 (0=absent, 3=severe) and the total was divided by the number of symptoms to provide an average score per symptom of 0-3. RMS was scored from 0 (no allergy rescue medication use per day) to 3 (at least one dose of systemic corticosteroid per day). The RMS score was not additive, and therefore the maximum RMS was 3 and the maximum CS was 6.

Time frame: 52-54 weeks after randomisation