Efficacy & Safety of STG320 Sublingual Tablets of HDM Allergen Extracts in Adults and Adolescents With HDM-associated AR

• Sponsor: Stallergenes Greer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02443805
• Collaborator: (none)
• Enrollment: 1,607
• Locations: 2
• Arms: 2
• Actual Duration (Months): 32.9
• Patients Per Site: 803.5
• Patients Per Site Per Month: 24.5

Study Details

Study Description

Brief Summary

The objective of this study was to assess the efficacy and safety of 12 months of treatment with 300 IR of STG320 sublingual tablets compared with placebo in adults and adolescents with HDM-associated allergic rhinitis.

Condition or Disease	Intervention/Treatment	Phase
Rhinitis, Allergic, Perennial; House Dust Mite Allergy	Biological: 300 IR; Biological: Placebo	Phase 3

Detailed Description

This study was a randomized, double-blind, placebo-controlled, phase III study with 2 parallel arms in adults and adolescents with HDM-associated allergic rhinitis (AR) for at least one year.

The primary objective was to assess the efficacy of STG320 sublingual tablets at a daily dosage of 300 IR when administered for 12 months to adults and adolescents with HDM-associated AR. The primary efficacy variable was the average Total Combined Score.

Study Design

• Study Type: Interventional
• Actual Enrollment: 1607 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-blind, Placebo-controlled, Multi-center Study of the Efficacy and Safety of STG320 Sublingual Tablets of House Dust Mite (HDM) Allergen Extracts in Adults and Adolescents With HDM-associated Allergic Rhinitis
• Actual Study Start Date: Sep 29, 2015
• Actual Primary Completion Date: Jun 25, 2018
• Actual Study Completion Date: Jun 25, 2018

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 300 IR 300 IR tablet of HDM Allergen Extracts	Biological: 300 IR; 300 IR tablet of HDM Allergen Extracts
Placebo Comparator: Placebo Placebo tablet	Biological: Placebo; Placebo tablet

Outcome Measures

Primary Outcome Measures

1. Total Combined Score [12 months]

   Average Total Combined Score (TCS), calculated for each patient as the average of the non-missing daily TCSs during the primary evaluation period. The daily TCS (scale 0-15) was the sum of the patient's daily Rhinitis Total Symptom Score (RTSS, scale 0-12) and daily Rescue Medication Score (RMS, scale 0-3). Lower is better.

Secondary Outcome Measures

1. Average Rhinitis Total Symptom Score (RTSS) [12 months]

   Average RTSS during the primary evaluation period. The daily Total Symptom Scores (RTSS) was the sum of the 4 rhinitis symptom scores: sneezing, rhinorrhoea, nasal pruritus and nasal congestion, each graded on a 4-point scale (0-3; 0: absent, 1: mild, 2: moderate, 3: severe). It ranges from 0 to 12. Lower is better.

2. Average Rescue Medication Score (RMS) [12 months]

   Average RMS during the primary evaluation period. Rescue Medication Score (RMS) ; range 0-3, lower is better.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Main Inclusion Criteria:

• Patients with HDM-associated allergic rhinitis (AR) for at least 1 year

• Patients sensitized to D. pteronyssinus (D. pte) and/or D. farinae (D. far) defined on skin prick test and HDM-specific serum IgE

Main Exclusion Criteria:

• A history of rhinitis, rhinoconjunctivitis or asthma to allergens other than HDM, likely to result in rhinitis symptoms during the evaluation periods

• Partly controlled or uncontrolled asthma

• Controlled asthma requiring controller treatment(s) consistent with GINA 2014 treatment Steps 3 to 5

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of South of Florida	Tampa	Florida	United States	33610
2	CHU Arnaud de Villeneuve	Montpellier		France	34295

Sponsors and Collaborators

• Stallergenes Greer

Investigators

• Principal Investigator: Pascal Demoly, MD, CHU Arnaud de Villeneuve, Montpellier, France
• Principal Investigator: Tom Casale, MD, University of South of Florida, Tampa, USA

Study Documents (Full-Text)

• Study Protocol - Oct 5, 2017
• Statistical Analysis Plan - Oct 29, 2018

More Information

Publications

None provided.

• Responsible Party: Stallergenes Greer
• ClinicalTrials.gov Identifier: NCT02443805
• Other Study ID Numbers: SL75.14
• First Posted: May 14, 2015
• Last Update Posted: Oct 14, 2019
• Last Verified: Sep 1, 2019

• Additional relevant MeSH terms: Rhinitis; Rhinitis, Allergic; Rhinitis, Allergic, Perennial

Study Results

Participant Flow

Recruitment Details	This study was conducted between 29 September 2015 (first patient, first visit) and 25 June 2018 (last patient, last visit).
Pre-assignment Detail	2,174 (50.9%) and 486 (11.4%) patients were excluded before and during the placebo run-in period, respectively. The main reason for screen failures at these two stages was a failure to meet randomization criteria.

Arm/Group Title	300 IR	Placebo
Arm/Group Description	300 IR tablet of HDM Allergen Extracts	Placebo tablet
Period Title: Overall Study
STARTED	802	805
COMPLETED	589	678
NOT COMPLETED	213	127

Baseline Characteristics

Arm/Group Title	300 IR	Placebo	Total
Arm/Group Description	300 IR tablet of HDM Allergen Extracts	Placebo tablet	Total of all reporting groups
Overall Participants	711	765	1476
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	29.5 (13.07)	29.6 (12.58)	29.6 (12.81)
Sex: Female, Male (Count of Participants)
Female	360 50.6%	396 51.8%	756 51.2%
Male	351 49.4%	369 48.2%	720 48.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	50 7%	46 6%	96 6.5%
Not Hispanic or Latino	660 92.8%	719 94%	1379 93.4%
Unknown or Not Reported	1 0.1%	0 0%	1 0.1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	1 0.1%	1 0.1%
Asian	21 3%	20 2.6%	41 2.8%
Native Hawaiian or Other Pacific Islander	2 0.3%	0 0%	2 0.1%
Black or African American	25 3.5%	37 4.8%	62 4.2%
White	660 92.8%	701 91.6%	1361 92.2%
More than one race	2 0.3%	3 0.4%	5 0.3%
Unknown or Not Reported	1 0.1%	3 0.4%	4 0.3%
Region of Enrollment (participants) [Number]
North America	212 29.8%	240 31.4%	452 30.6%
Europe	453 63.7%	477 62.4%	930 63%
Israel	23 3.2%	23 3%	46 3.1%
Russia	23 3.2%	25 3.3%	48 3.3%

Outcome Measures

1. Primary Outcome

Title	Total Combined Score
Description	Average Total Combined Score (TCS), calculated for each patient as the average of the non-missing daily TCSs during the primary evaluation period. The daily TCS (scale 0-15) was the sum of the patient's daily Rhinitis Total Symptom Score (RTSS, scale 0-12) and daily Rescue Medication Score (RMS, scale 0-3). Lower is better.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

The FAS included all randomized patients (pts) who received at least one dose of the IP of treatment period and had at least one primary efficacy evaluation during the overall treatment period: 1,476 pts. Among these pts, only those with efficacy evaluation during the primary evaluation period were included in the primary analysis: 1,262 pts.

Arm/Group Title	300 IR	Placebo
Arm/Group Description	300 IR tablet of HDM Allergen Extracts	Placebo tablet
Measure Participants	586	676
Least Squares Mean (95% Confidence Interval) [Units on a scale]	3.62	4.35

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	300 IR, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Source Model: Type III effects Covariates: Treatment group, Gender, Age Class, Sensitization Status, Asthma Status, Pooled Center, Baseline Average RTSS.
	Method	ANCOVA
	Comments

2. Secondary Outcome

Title	Average Rhinitis Total Symptom Score (RTSS)
Description	Average RTSS during the primary evaluation period. The daily Total Symptom Scores (RTSS) was the sum of the 4 rhinitis symptom scores: sneezing, rhinorrhoea, nasal pruritus and nasal congestion, each graded on a 4-point scale (0-3; 0: absent, 1: mild, 2: moderate, 3: severe). It ranges from 0 to 12. Lower is better.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

The FAS included all randomized patients (pts) who received at least one dose of the IP of treatment period and had at least one primary efficacy evaluation during the overall treatment period: 1,476 pts. Among these pts, only those with efficacy evaluation during the primary evaluation period were included in the secondary analysis: 1,262 pts.

Arm/Group Title	300 IR	Placebo
Arm/Group Description	300 IR tablet of HDM Allergen Extracts	Placebo tablet
Measure Participants	586	676
Least Squares Mean (95% Confidence Interval) [Units on a scale]	3.16	3.79

3. Secondary Outcome

Title	Average Rescue Medication Score (RMS)
Description	Average RMS during the primary evaluation period. Rescue Medication Score (RMS) ; range 0-3, lower is better.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

The FAS included all randomized patients (pts) who received at least one dose of the IP of treatment period and had at least one primary efficacy evaluation during the overall treatment period: 1,476 pts. Among these pts, only those with efficacy evaluation during the primary evaluation period were included in the secondary analysis: 1,262 pts.

Arm/Group Title	300 IR	Placebo
Arm/Group Description	300 IR tablet of HDM Allergen Extracts	Placebo tablet
Measure Participants	586	676
Least Squares Mean (95% Confidence Interval) [Units on a scale]	0.21	0.30

Adverse Events

Time Frame	12 months
Adverse Event Reporting Description	Safety variables were adverse events (AEs) monitored throughout the study and data from physical examinations and clinical laboratory assessments. 1,607 patients were randomized. 6 patients randomized by mistake did not receive any IP of the treatment period and were excluded from the Safety Set. Accordingly, the Safety Set comprised 1,601 patients.
Arm/Group Title	300 IR		Placebo
Arm/Group Description	300 IR tablet of HDM Allergen Extracts		Placebo tablet
All Cause Mortality
	300 IR		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/800 (0%)		0/801 (0%)
Serious Adverse Events
	300 IR		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	21/800 (2.6%)		9/801 (1.1%)
Blood and lymphatic system disorders
Neutropenia	1/800 (0.1%)		0/801 (0%)
Cardiac disorders
Atrial fibrillation	1/800 (0.1%)		0/801 (0%)
Ear and labyrinth disorders
Meniere's disease	0/800 (0%)		1/801 (0.1%)
Gastrointestinal disorders
Diarrhoea	1/800 (0.1%)		0/801 (0%)
General disorders
Chest pain	1/800 (0.1%)		0/801 (0%)
Chronic fatigue syndrome	0/800 (0%)		1/801 (0.1%)
Infections and infestations
Appendicitis	3/800 (0.4%)		0/801 (0%)
Tick-borne viral encephalitis	1/800 (0.1%)		0/801 (0%)
Tonsillitis	1/800 (0.1%)		0/801 (0%)
Cellulitis	0/800 (0%)		1/801 (0.1%)
Pneumonia	0/800 (0%)		1/801 (0.1%)
Injury, poisoning and procedural complications
Ankle fracture	1/800 (0.1%)		1/801 (0.1%)
Joint dislocation	1/800 (0.1%)		0/801 (0%)
Pelvic fracture	0/800 (0%)		1/801 (0.1%)
Spinal fracture	0/800 (0%)		1/801 (0.1%)
Musculoskeletal and connective tissue disorders
Chondromalacia	1/800 (0.1%)		0/801 (0%)
Plica syndrome	1/800 (0.1%)		0/801 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer	1/800 (0.1%)		0/801 (0%)
Invasive ductal breast carcinoma	1/800 (0.1%)		0/801 (0%)
Thyroid neoplasm	1/800 (0.1%)		0/801 (0%)
Hodgkin's disease	0/800 (0%)		1/801 (0.1%)
Uterine leiomyoma	0/800 (0%)		1/801 (0.1%)
Nervous system disorders
Intracranial aneurysm	0/800 (0%)		1/801 (0.1%)
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous	1/800 (0.1%)		0/801 (0%)
Psychiatric disorders
Anxiety	1/800 (0.1%)		0/801 (0%)
Renal and urinary disorders
Renal colic	1/800 (0.1%)		0/801 (0%)
Nephrolithiasis	0/800 (0%)		1/801 (0.1%)
Reproductive system and breast disorders
Ovarian cyst ruptured	1/800 (0.1%)		0/801 (0%)
Respiratory, thoracic and mediastinal disorders
Pharyngeal disorder	2/800 (0.3%)		0/801 (0%)
Skin and subcutaneous tissue disorders
Dermatitis atopic	2/800 (0.3%)		0/801 (0%)
Other (Not Including Serious) Adverse Events
	300 IR		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	424/800 (53%)		223/801 (27.8%)
Ear and labyrinth disorders
Ear pruritus	115/800 (14.4%)		13/801 (1.6%)
Gastrointestinal disorders
Oral pruritus	189/800 (23.6%)		29/801 (3.6%)
Oedema mouth	112/800 (14%)		3/801 (0.4%)
Tongue oedema	68/800 (8.5%)		3/801 (0.4%)
Lip oedema	61/800 (7.6%)		8/801 (1%)
Dysphagia	53/800 (6.6%)		2/801 (0.2%)
Nausea	47/800 (5.9%)		8/801 (1%)
Abdominal pain upper	43/800 (5.4%)		12/801 (1.5%)
Infections and infestations
Nasopharyngitis	107/800 (13.4%)		117/801 (14.6%)
Nervous system disorders
Headache	57/800 (7.1%)		68/801 (8.5%)
Respiratory, thoracic and mediastinal disorders
Throat irritation	136/800 (17%)		27/801 (3.4%)
Pharyngeal oedema	46/800 (5.8%)		1/801 (0.1%)
Oropharyngeal pain	45/800 (5.6%)		31/801 (3.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS 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.