LLB-2016-01: Efficacy of 2LALERG (Homeopathic Drug) in Allergic Rhinitis Related to Grass Pollen

• Sponsor: Labo'Life (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02690935
• Collaborator: (none)
• Enrollment: 102
• Location: 1
• Arms: 2
• Duration (Months): 13.2
• Patients Per Site Per Month: 7.7

Study Details

Study Description

Brief Summary

The primary objective of this study is to demonstrate the superiority of 2L®ALERG over placebo in terms of efficacy on the symptoms of allergic rhinitis and allergic rhinoconjunctivitis in patients with seasonal allergy to grass pollen, corrected according to rescue medication intake. The secondary objectives are to compare the allergy symptoms, the rescue medication intake, the quality of life and the safety in patients treated with 2L®ALERG or with a placebo.

This is a multicentre, randomized, double-blind, two-parallel group, interventional placebo-controlled study with a notified homeopathic medication, marketed since 2002.

Fifty patients will be recruited per group to achieve 40 cases completed per group, i.e., a total of 100 patients included for 80 cases completed.

Screening will be done before the peak of pollination and the treatment will be set up two months before traditional pollen peak, then visits at 3 months and 6 months, or end of the peak.

The treatment will consist of 1 capsule daily, fasting morning, following the numerical order of 1 to 10 capsules for 6 months.

The placebo will have the same form, colour, taste and aspect. The allowed concomitant treatments are the already established treatments for associated pathologies not liable to have an impact on the proper conduct of the study and the rescue medications allowed in the first-line adjuvant treatment (oral or topical antihistamines [nasal or eye] and eye cromoglycate, topical nasal corticosteroids [in case of failure or insufficiency of those above]).

The prohibited treatments are the oral or injectable corticosteroids and the anti-leukotrienes.

Condition or Disease	Intervention/Treatment	Phase
Seasonal Allergy	Drug: 2LALERG; Drug: Placebo	Phase 4

Detailed Description

The primary objective of this study is to demonstrate the superiority of 2L®ALERG over placebo in terms of efficacy on the symptoms of allergic rhinitis and allergic rhinoconjunctivitis in patients with seasonal allergy to grass pollen, corrected according to rescue medication intake. The secondary objectives are to compare the allergy symptoms, the rescue medication intake, the quality of life and the safety in patients treated with 2L®ALERG or with a placebo.

This is a multicentre, randomized, double-blind, two-parallel group, interventional placebo-controlled study with a notified homeopathic medication, marketed since 2002.

Fifty patients will be recruited per group to achieve 40 cases completed per group, i.e., a total of 100 patients included for 80 cases completed.

Screening will be done before the peak of pollination and the treatment will be set up two months before traditional pollen peak, then visits at 3 months and 6 months, or end of the peak.

The treatment will consist of 1 capsule daily, fasting morning, following the numerical order of 1 to 10 capsules for 6 months.

The placebo will have the same form, colour, taste and aspect. The allowed concomitant treatments are the already established treatments for associated pathologies not liable to have an impact on the proper conduct of the study and the rescue medications allowed in the first-line adjuvant treatment (oral or topical antihistamines [nasal or eye] and eye cromoglycate, topical nasal corticosteroids [in case of failure or insufficiency of those above]).

The prohibited treatments are the oral or injectable corticosteroids and the anti-leukotrienes.

The following demographic data will be collected during the first visit: date of birth, gender, ethnic group, weight, height, smoking habits and alcohol use status.

Medical history, treatment history, concomitant treatments and patient's physical examination will also be documented during V0.

The allergy must be confirmed by positive skin test and/or the presence of IgE for grasses (prick test defined as positive if higher than or equal to half the negative control; IgE are positive if at least class 3 (≥ 3.5 kU / L); these tests must have been made at the latest during the first visit.

A patient diary will be given to each patient:

• For evaluation of the total 5 symptoms score T5SS and rescue medication RS, it is essential that patients note every day the symptoms (sneezing, rhinorrhoea, nasal pruritus, itching and/or eye tearing and nasal obstruction) intensity, and the rescue medications, in their patient diary.

• It is also essential that the patient takes note every day of his/her QoL by filling in three questions included in his/her diary card: Did you sleep well? - Can you work normally? - How do you feel?

• It is also imperative that patients note the date of the start of treatment and the date of onset of symptoms.

This patient diary will be given to the patient at each visit, and will be brought back at the next visit, it will be reviewed and validated by the investigator and will be part of the Case Report Form.

All relevant (related to allergy) concomitant medications taken by the patient during the study period will be recorded at each visit in the CRF.

The AEs and SAEs will be recorded at V1 and V2 in order to assess safety.

Study Design

• Study Type: Interventional
• Actual Enrollment: 102 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Randomized, Double-blind, Placebo-controlled Study to Measure 2L®ALERG (Homeopathic Drug) Efficacy on Symptoms of Allergic Rhinitis and Allergic Rhinoconjunctivitis in Patients With a Seasonal Allergy to Grass Pollen
• Study Start Date: Mar 1, 2016
• Actual Primary Completion Date: Apr 7, 2017
• Actual Study Completion Date: Apr 7, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 2LALERG Interleukin 1: 17 CH Interleukin 4: 17-27 CH Interleukin 5: 17 CH Interleukin 6: 17 CH Interleukin 10: 17 CH Interleukin 12: 9 CH Interleukin 13: 17 CH Tumor Necrosis Factor Alpha: 17 CH Transforming Growth Factor Beta: 5 CH Pulmo histaminum: 15 CH SNA-HLA-II: 18 CH Impregnated on lactose saccharose globules (380 mg/capsule)	Drug: 2LALERG; Homeopathic drug; Other Names: Immunotherapy
Placebo Comparator: Placebo Non-impregnated lactose saccharose globules (380 mg/capsule)	Drug: Placebo; Placebo

Outcome Measures

Primary Outcome Measures

1. Area Under the Curve [AUC](Total Score of Symptoms Taking Into Account the Total 5 Symptom Score (T5SS) and Consumption of Rescue Medications (RM) on the Y-axis, and Time on X Axis) [Up to Month 6 (end of pollen season)]

   Area under the curve [AUC] (total score of symptoms taking into account the Total 5 Symptom Score (T5SS) and consumption of rescue medications (RM) on the Y-axis versus time on X axis). T5SS was the sum of the 5 individual scores (min-max=0-15). It was corrected each day as a function of consumption of rescue medications (RM): oral antihistamine (+2 points), local treatment (nasal or eye; +1 point), ocular cromoglycate (+1 point) and nasal topical corticosteroids (+1 point). An increase in the total corrected score was considered as a worsening of the allergic symptoms.

Secondary Outcome Measures

1. Quality of Life During the Whole Period of Observation [QoL scores were assessed daily for up to 6 months]

   This is the mean of the score to 3 daily quality of life questions: 1) Did you sleep well (0 to 3), 2) Are you able to work (0 to 3), 3) How do you feel today (0 to 3). The minimum daily score is 0 (good quality of life) and the maximum is 9 (bad quality of life). The mean of the daily scores was calculated over the whole period of observation (up to 6 months) for each patient.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age ≥18 years, male and female

• Woman of childbearing age using effective contraceptive means

• Patient having the faculties to understand and respect the constraints of the study

• Symptomatic since at least two seasons and confirmed by positive skin test and/or the presence of IgE for grasses (prick test defined as positive if higher than or equal to half the negative control; IgE positive if at least class 3 (≥ 3.5 kU / L); these tests must have been performed at the latest at the first screening visit

• Signature of the Informed Consent Form

Exclusion Criteria:

• Pregnant woman or woman wishing to become pregnant

• Breastfeeding woman

• Patient with an acute exacerbation of allergic rhinitis

• Patient with uncontrolled asthma

• Immunotherapy received within the last two years

• Patient with a known lactose intolerance

• Patient who participated in a clinical study in the previous three months

• Patient who is not sufficiently motivated to engage on a follow-up period of 6 months or more, unable to complete the patient diary, or likely to travel or to move before the end of the study,

• Patient taking nasal or bronchial inhaled corticosteroids on a long term basis (intermittent consumption during the season is permitted provided it is mentioned in the patient's records)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	ResearchLink	Linkebeek		Belgium	1630

Sponsors and Collaborators

• Labo'Life

Investigators

• Principal Investigator: Stéphane Heijmans, MD, ResearchLink

Study Documents (Full-Text)

• Study Protocol - Feb 4, 2016
• Statistical Analysis Plan - Feb 29, 2016

More Information

Publications

None provided.

• Responsible Party: Labo'Life
• ClinicalTrials.gov Identifier: NCT02690935
• Other Study ID Numbers: LLB-2016-01
• First Posted: Feb 24, 2016
• Last Update Posted: Sep 30, 2020
• Last Verified: Oct 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Labo'Life: grass pollen; homeopathy; placebo; quality of life
• Additional relevant MeSH terms: Rhinitis; Rhinitis, Allergic; Rhinitis, Allergic, Seasonal; Hypersensitivity

Study Results

Participant Flow

Recruitment Details	The first patient was enrolled in the study on 05 March 2016 and the last study visit was on 29 November 2016.

Arm/Group Title	2LALERG	Placebo
Arm/Group Description	Interleukin 1: 17 CH Interleukin 4: 17-27 CH Interleukin 5: 17 CH Interleukin 6: 17 CH Interleukin 10: 17 CH Interleukin 12: 9 CH Interleukin 13: 17 CH Tumor Necrosis Factor Alpha: 17 CH Transforming Growth Factor Beta: 5 CH Pulmo histaminum: 15 CH SNA-HLA-II: 18 CH Impregnated on lactose saccharose globules (380 mg/capsule) 2LALERG: Homeopathic drug	Non-impregnated lactose saccharose globules (380 mg/capsule) Placebo: Placebo
Period Title: Overall Study
STARTED	51	51
COMPLETED	51	51
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	2LALERG	Placebo	Total
Arm/Group Description	Interleukin 1: 17 CH Interleukin 4: 17-27 CH Interleukin 5: 17 CH Interleukin 6: 17 CH Interleukin 10: 17 CH Interleukin 12: 9 CH Interleukin 13: 17 CH Tumor Necrosis Factor Alpha: 17 CH Transforming Growth Factor Beta: 5 CH Pulmo histaminum: 15 CH SNA-HLA-II: 18 CH Impregnated on lactose saccharose globules (380 mg/capsule) 2LALERG: Homeopathic drug	Non-impregnated lactose saccharose globules (380 mg/capsule) Placebo: Placebo	Total of all reporting groups
Overall Participants	51	51	102
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	39.5 (14.5)	40.7 (15.1)	40.1 (14.8)
Sex: Female, Male (Count of Participants)
Female	23 45.1%	26 51%	49 48%
Male	28 54.9%	25 49%	53 52%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	51 100%	51 100%	102 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
Belgium	51 100%	51 100%	102 100%

Outcome Measures

1. Primary Outcome

Title	Area Under the Curve [AUC](Total Score of Symptoms Taking Into Account the Total 5 Symptom Score (T5SS) and Consumption of Rescue Medications (RM) on the Y-axis, and Time on X Axis)
Description	Area under the curve [AUC] (total score of symptoms taking into account the Total 5 Symptom Score (T5SS) and consumption of rescue medications (RM) on the Y-axis versus time on X axis). T5SS was the sum of the 5 individual scores (min-max=0-15). It was corrected each day as a function of consumption of rescue medications (RM): oral antihistamine (+2 points), local treatment (nasal or eye; +1 point), ocular cromoglycate (+1 point) and nasal topical corticosteroids (+1 point). An increase in the total corrected score was considered as a worsening of the allergic symptoms.
Time Frame	Up to Month 6 (end of pollen season)

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	2LALERG	Placebo
Arm/Group Description	Interleukin 1: 17 CH Interleukin 4: 17-27 CH Interleukin 5: 17 CH Interleukin 6: 17 CH Interleukin 10: 17 CH Interleukin 12: 9 CH Interleukin 13: 17 CH Tumor Necrosis Factor Alpha: 17 CH Transforming Growth Factor Beta: 5 CH Pulmo histaminum: 15 CH SNA-HLA-II: 18 CH Impregnated on lactose saccharose globules (380 mg/capsule) 2LALERG: Homeopathic drug	Non-impregnated lactose saccharose globules (380 mg/capsule) Placebo: Placebo
Measure Participants	49	47
Mean (Standard Deviation) [T5SS score corrected with RM * day]	2.76 (1.89)	2.97 (2.48)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	2LALERG, Placebo
	Comments	H0: The efficacy of 2LALERG and placebo are similar H1: The efficacy of 2LALERG and placebo are different
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.642
	Comments	No adjustment of the p-value
	Method	t-test, 2 sided
	Comments

2. Secondary Outcome

Title	Quality of Life During the Whole Period of Observation
Description	This is the mean of the score to 3 daily quality of life questions: 1) Did you sleep well (0 to 3), 2) Are you able to work (0 to 3), 3) How do you feel today (0 to 3). The minimum daily score is 0 (good quality of life) and the maximum is 9 (bad quality of life). The mean of the daily scores was calculated over the whole period of observation (up to 6 months) for each patient.
Time Frame	QoL scores were assessed daily for up to 6 months

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	2LALERG	Placebo
Arm/Group Description	Interleukin 1: 17 CH Interleukin 4: 17-27 CH Interleukin 5: 17 CH Interleukin 6: 17 CH Interleukin 10: 17 CH Interleukin 12: 9 CH Interleukin 13: 17 CH Tumor Necrosis Factor Alpha: 17 CH Transforming Growth Factor Beta: 5 CH Pulmo histaminum: 15 CH SNA-HLA-II: 18 CH Impregnated on lactose saccharose globules (380 mg/capsule) 2LALERG: Homeopathic drug	Non-impregnated lactose saccharose globules (380 mg/capsule) Placebo: Placebo
Measure Participants	49	47
Mean (Standard Deviation) [units on a scale]	0.84 (0.88)	0.81 (0.81)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	2LALERG, Placebo
	Comments	H0: 2LALERG and placebo have the same effect on the quality of life H1: 2LALERG and placebo do not have the same effect on the quality of life
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.829
	Comments	No adjustment for multiplicity
	Method	t-test, 2 sided
	Comments

Adverse Events

Time Frame	6 months
Arm/Group Title	2LALERG		Placebo
Arm/Group Description	Interleukin 1: 17 CH Interleukin 4: 17-27 CH Interleukin 5: 17 CH Interleukin 6: 17 CH Interleukin 10: 17 CH Interleukin 12: 9 CH Interleukin 13: 17 CH Tumor Necrosis Factor Alpha: 17 CH Transforming Growth Factor Beta: 5 CH Pulmo histaminum: 15 CH SNA-HLA-II: 18 CH Impregnated on lactose saccharose globules (380 mg/capsule) 2LALERG: Homeopathic drug		Non-impregnated lactose saccharose globules (380 mg/capsule) Placebo: Placebo
All Cause Mortality
	2LALERG		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/51 (0%)		0/51 (0%)
Serious Adverse Events
	2LALERG		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/51 (2%)		2/51 (3.9%)
Cardiac disorders
Atrial fibrillation	0/51 (0%)	0	1/51 (2%)	1
Nervous system disorders
Transient ischemic attack	0/51 (0%)	0	1/51 (2%)	1
Psychiatric disorders
Cocaine abuse	1/51 (2%)	1	0/51 (0%)	0
Renal and urinary disorders
Nephrolithiasis	0/51 (0%)	0	1/51 (2%)	1
Other (Not Including Serious) Adverse Events
	2LALERG		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/51 (13.7%)		7/51 (13.7%)
Gastrointestinal disorders
Enteritis	3/51 (5.9%)	3	1/51 (2%)	1
Infections and infestations
Bronchitis	3/51 (5.9%)	3	0/51 (0%)	0
Rhinitis	1/51 (2%)	1	3/51 (5.9%)	3
Respiratory, thoracic and mediastinal disorders
Cough	0/51 (0%)	0	3/51 (5.9%)	3

Limitations/Caveats

Allergy cases were mainly prevalent and chronic. Many concomitant drugs were taken Patients were older in this trial compared to Van der Brempt et al. (2011)

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.