VALERGEN-combination of routes- Asthma-Adults-Phase II

General information

Section to complete general information about the trial: scientific and public title, protocol identifiers, sponsors and Source(s) of Monetary or Material Support.

Scientific title:

Evaluation of the therapeutic effect and safety of the combination of SC and SL routes in allergen-specific immunotherapy with extracts of house dust mites in asthmatic patients sensitized to these mites. Phase II clinical trial.

Secondary indentifying numbers:

GEC2019DPDSBT022

Issuing authority of the secondary identifying numbers:

National Center of Bioproducts (BioCen)

Source(s) of monetary or material support:

National Center of Bioproducts (BioCen)Cuban Ministry of Public Health (Minsap)

Authorization for beginning

Section to complete information about the regulatory approval of clinical trial: regulatory agency name, approval date and reference number in the agency.

Regulatory instance to authorize the initiation of the study:

Center for State Control of Drugs, Medical Devices and Equipment (CECMED)

Authorization date :

15/05/2019

Reference number:

511/05.001.19BNV

Principal investigator

Section to complete information about Email address, telephone number and postal address of the Principal Investigator.

First name:

Iglermys

Last name:

Figueroa Garcia

Medical Specialty :

First Degree specialist in Allergy and Integral General Medicine

Affiliation:

Surgical Clinical Hospital “Hermanos Ameijeiras”.

Postal address:

701 San Lazaro Ave. Corner to Belascoain.

City:

Havana

País:

Cuba

Zip Code:

10300

Telephone:

+53-78761898

+53-78761899

Email address:

iglermis@infomed.sld.cu [1]

Clinical sites to participate

Section to complete the data related to the clinical sites involved in the trial: site and responsible investigator for every site.

Countries of recruitment:

Cuba

Clinical sites:

Havana, 43 Clinic , Omar Herrera Barrios, MD, First degree specialist in Allergy and Second degree specialist in Internal Medicine

Research ethics committees:

Surgical Clinical Hospital “Hermanos Ameijeiras”, in review.

43 Clinic, in review.

Recruitment status

Section to complete information about the recruitment status and the date of first enrolment subject

Recruitment status:

Pending

Date of first enrollment:

01/07/2020

Health condition and Intervention

Section to complete information about the primary medical condition(s) or problem(s) studied and, a characteristics of the intervention(s).

Health condition(s) or Problem(s) studied:

Asthma

Health condition(s) code:

Asthma

Bronchial Diseases

Lung Diseases, Obstructive

Lung Diseases

Respiratory Tract Diseases

Respiratory Hypersensitivity

Hypersensitivity, Immediate

Hypersensitivity

Immune System Diseases

Environmental Illness

Intervention(s):

Group A: VALERGEN DP; Group B: VALERGEN DS; Group C: VALERGEN BT. In each group there are 3 schemes. Scheme 1: Subcutaneous route (SC) Scheme 2: Sublingual route (SL) Scheme 3: Subcutaneous route (SC) in increasing phase and, sublingual route (SL) in maintenance phase Group A1 VALERGEN DP by SL route (Control): - Increasing phase: Vaccination daily for 23 days in volumes of 1, 2, 3, 4, 6, 8 and 10 drops according to day 1, 2, 3, 4, 5, 6, and 7 of the week, respectively. Week 1 (day 1 to 7. Concentration of 200 UB/mL), week 2 (day 8 to 14. Concentration of 2000 UB/mL), week 3 (day 15 to 21. Concentration of 20000 UB/mL) and week 4 (day 22 and 23. Concentration of 200000 UB/mL). - Maintenance phase: 2 drops twice a week, until completing 6 months of treatment (Concentration of 200000 UB/mL). Group A2 VALERGEN DP by SC route (Control): - Increasing phase: Weekly vaccination for 13 weeks. Weeks 1 to 3 (Concentration of 20 UB/mL, volumes 0.2, 0.5 and 1mL respectively), Weeks 4 to 6 (Concentration of 200 UB/mL, volumes 0.2, 0.5 and 1mL respectively), Weeks 7 to 10 (Concentration of 2000 UB/mL, volumes 0.2, 0.4, 0.6 and 0.8mL respectively), weeks 11 to 13 (Concentration of 20000 UB/mL, volumes 0.1, 0.2 and 0.3mL respectively). - Maintenance phase: Concentration of 20000 UB/mL, volume 0.3mL. Monthly vaccination until completing 6 months of treatment. Group A3 VALERGEN DP by SC and SL route (Experimental): - Increasing phase: Vaccination by SC route. Weekly vaccination for 13 weeks. Weeks 1 to 3 (Concentration of 20 UB/mL, volumes 0.2, 0.5 and 1mL respectively), Weeks 4 to 6 (Concentration of 200 UB/mL, volumes 0.2, 0.5 and 1mL respectively), Weeks 7 to 10 (Concentration of 2000 UB/mL, volumes 0.2, 0.4, 0.6 and 0.8mL respectively), weeks 11 to 13 (Concentration of 20000 UB/mL, volumes 0.1, 0.2 and 0.3mL respectively). - Maintenance phase: SL vaccination. Week 14, a drop twice a week (Concentration of 200,000 UB / mL). From week 15, continue with 2 drops twice a week until completing 6 months of treatment. Group B1 VALERGEN DS by SL route (Control): - Increasing phase: Vaccination daily for 23 days in volumes of 1, 2, 3, 4, 6, 8 and 10 drops according to day 1, 2, 3, 4, 5, 6, and 7 of the week, respectively. Week 1 (day 1 to 7. Concentration of 200 UB/mL), week 2 (day 8 to 14. Concentration of 2000 UB/mL), week 3 (day 15 to 21. Concentration of 20000 UB/mL) and week 4 (day 22 and 23. Concentration of 200000 UB/mL). - Maintenance phase: 2 drops twice a week, until completing 6 months of treatment (Concentration of 200000 UB/mL). Group B2 VALERGEN DS by SC route (Control): - Increasing phase: Weekly vaccination for 13 weeks. Weeks 1 to 3 (Concentration of 20 UB/mL, volumes 0.2, 0.5 and 1mL respectively), Weeks 4 to 6 (Concentration of 200 UB/mL, volumes 0.2, 0.5 and 1mL respectively), Weeks 7 to 10 (Concentration of 2000 UB/mL, volumes 0.2, 0.4, 0.6 and 0.8mL respectively), weeks 11 to 13 (Concentration of 20000 UB/mL, volumes 0.1, 0.2 and 0.3mL respectively). - Maintenance phase: Concentration of 20000 UB/mL, volume 0.3mL. Monthly vaccination until completing 6 months of treatment. Group B3 VALERGEN DS by SC and SL route (Experimental): - Increasing phase: Vaccination by SC route. Weekly vaccination for 13 weeks. Weeks 1 to 3 (Concentration of 20 UB/mL, volumes 0.2, 0.5 and 1mL respectively), Weeks 4 to 6 (Concentration of 200 UB/mL, volumes 0.2, 0.5 and 1mL respectively), Weeks 7 to 10 (Concentration of 2000 UB/mL, volumes 0.2, 0.4, 0.6 and 0.8mL respectively), weeks 11 to 13 (Concentration of 20000 UB/mL, volumes 0.1, 0.2 and 0.3mL respectively). - Maintenance phase: SL vaccination. Week 14, a drop twice a week (Concentration of 200,000 UB / mL). From week 15, continue with 2 drops twice a week until completing 6 months of treatment. Group C1 VALERGEN BT by SL route (Control): - Increasing phase: Vaccination daily for 23 days in volumes of 1, 2, 3, 4, 6, 8 and 10 drops according to day 1, 2, 3, 4, 5, 6, and 7 of the week, respectively. Week 1 (day 1 to 7. Concentration of 200 UB/mL), week 2 (day 8 to 14. Concentration of 2000 UB/mL), week 3 (day 15 to 21. Concentration of 20000 UB/mL) and week 4 (day 22 and 23. Concentration of 200000 UB/mL). - Maintenance phase: 2 drops twice a week, until completing 6 months of treatment (Concentration of 200000 UB/mL). Group C2 VALERGEN BT by SC route (Control): - Increasing phase: Weekly vaccination for 13 weeks. Weeks 1 to 3 (Concentration of 20 UB/mL, volumes 0.2, 0.5 and 1mL respectively), Weeks 4 to 6 (Concentration of 200 UB/mL, volumes 0.2, 0.5 and 1mL respectively), Weeks 7 to 10 (Concentration of 2000 UB/mL, volumes 0.2, 0.4, 0.6 and 0.8mL respectively), weeks 11 to 13 (Concentration of 20000 UB/mL, volumes 0.1, 0.2 and 0.3mL respectively). - Maintenance phase: Concentration of 20000 UB/mL, volume 0.3mL. Monthly vaccination until completing 6 months of treatment. Group C3 VALERGEN BT by SC and SL route (Experimental): - Increasing phase: Vaccination by SC route. Weekly vaccination for 13 weeks. Weeks 1 to 3 (Concentration of 20 UB/mL, volumes 0.2, 0.5 and 1mL respectively), Weeks 4 to 6 (Concentration of 200 UB/mL, volumes 0.2, 0.5 and 1mL respectively), Weeks 7 to 10 (Concentration of 2000 UB/mL, volumes 0.2, 0.4, 0.6 and 0.8mL respectively), weeks 11 to 13 (Concentration of 20000 UB/mL, volumes 0.1, 0.2 and 0.3mL respectively). - Maintenance phase: SL vaccination. Week 14, a drop twice a week (Concentration of 200,000 UB / mL). From week 15, continue with 2 drops twice a week until completing 6 months of treatment.

Intervention code:

Allergens

Antigens, Dermatophagoides

Desensitization, Immunologic

Sublingual Immunotherapy

Injections, Subcutaneous

Intervention keyword:

allergenic extract Blomia tropicalis Dermatophagoides pteronyssinus Dermatophagoides siboney VALERGEN-BT VALERGEN DP VALERGEN DS

Outcomes and Timepoint

Section to complete information about primary and secondary outcomes including. It includes the metric or method of measurement used and, the time point for every outcome.

Primary outcome(s):

Symptoms and medication for asthma [Symptoms rating (shortness of breath, cough, sputum, wheezing and chest tightness). Each symptom 1 point, maximum of 5 points per day. Points will be added by the intensity 0: symptoms disappear spontaneously, 1: If necessary self-administered home therapy (tablets, syrups and sprays pressurized bronchodilators), 2: If the patient will need to attend the consultation of the research team or the emergency guard of any instance, 3: If the patient requires hospitalization. Need medication Scoring: 3-point scale (0 = no use, 1 = use of beta-2 agonists, methylxanthines, ephedrine, adrenaline, inhaled steroids 2 = use of systemic steroids). The compound variable of symptoms and medication will be calculated as the simple sum of both scores. Measuring time: daily, during the month before treatment start and, during the 6 months of treatment.

Key secondary outcomes:

1. Symptoms and medication for rhinitis: Symptom score (Pruritus, Secretion, Nasal obstruction, Sneezing, Itching / Red eyes, Tearing). Each symptom evaluated can reach a value of 0 to 3 points according to: 0 points: no symptoms, 1 point: slight symptoms (signs / symptoms clearly present, but minimal discomfort, well tolerated), 2 points: moderate symptoms (definite awareness of signs / symptoms that are annoying but tolerated), 3 points: severe symptoms (signs / symptoms that are difficult to tolerate, interfere with activities of daily living and / or sleep). Score for medication need: 1 point: Oral or topical H1 antihistamines, 2 points: Topical corticosteroids, 3 points: Oral corticosteroids. The variable composed of symptoms and medication will be calculated as the simple sum of both scores. Measurement time: daily, during the 30 days before treatment star and, during the 6 months of treatment. 2. Allergen-specific skin reactivity (Ch10, allergen concentration equivalent to a wheal area equal to that produced by Histamine HCl 10 mg / mL). Measurement time: At baseline and, 6 months. 3. Determination of Peak Expiratory Flow (PEF), using standard meter of PEF Measuring time: twice a day during the 30 days before treatment start and, during the 6 months of treatment 4. Quality of life (Quality of life questionnaire AQLQ (S), JUNIPER). Measuring time: At baseline and, 6 months. 5. Control test of Allergic Rhinitis and Asthma (According to the CARAT questionnaire) Measurement time: At baseline and, 6 months. 6. Allergen-specific antibodies (Values of IgE and IgG4 using ELISA technique). Measuring time: At baseline and, 6 months. 7. Adverse events-AE (Occurrence of AE (Yes, No); Type of AE (Name of AE according to clinical manifestation); Localization of the AE (WAO classification: Local, Systemic Grade 1, Systemic Grade 2, Systemic Grade 3, Systemic Grade 4, Systemic Grade 5); Time of appearance (Time from the administration of the drug until the appearance of the AE: Immediate ≤ 30 minutes, Late> 30 minutes); Duration of the AE (Time from start to end of the AE); Prior knowledge (Expected, Unexpected); Intensity of the AE (Mild, Moderate, Severe); Consequence of the AE (Serious, Not Serious); Causality (Very probable, Probable, Possible, Unlikely, Not related, Not assessable/Not classifiable); Outcome of the AE (Recovered, Not Recovered, Recovered with sequels, Death, Unknown); Attitude regarding the treatment of the study (Continuation, Definitive interruption)). Measuring time: daily for 6 months.

Selection criterias

Section to complete information about the inclusion and exclusion criteria for participant selection, including age and gender.

Gender:

Male/Female

Minimum age:

18 years

Maximum age:

50 years

Inclusion criteria:

1. Allergic asthmatic patients with a positive history of allergic symptoms caused by house dust. 2. Positive skin test to one of the three mites greater than or equal to 3 mm (VALERGEN DP, VALERGEN DS or VALERGEN BT, 20 000 UB / mL) and skin test negative to the other two or positive, but with a smaller diameter. 3. Patients included in the study are patients diagnosed clinically as extrinsic asthmatics, which are classified as intermittent or persistent mild or moderate according to international guidelines for asthma (GINA, Global Initiative for Asthma) 4. Age between 18 and 50. 5. Patients express written consent to participate in the trial.

Exclusion criteria:

1. Patients previously treated with immunotherapy with allergenic extracts in the previous five years. 2. Patients classified as Intermittent or severe persistent asthma. 3. Diagnosed autoimmune disease of any kind. 4. Generalized severe eczema. 5. Patients with tumor disease. 6. Patients treated with beta-blockers. 7. Patients where the use of adrenaline is contraindicated (hypertension). 8. Pregnancy and lactation (pregnancy tests will be performed on females). 9. Patients at least one year prior to the study required immunostimulant or immunosuppressive treatment (except corticosteroids), including interferons, cyclosporin A and natural immunomodulators (Vimang Biomodulina) 10. Patients with a history of psychiatric disorders that compromise data collection and adherence to treatment.

Type of population:

Adults

Type of participant:

Patients

Study design

Section to complete information about the characteristics of the study design.

Type study:

Interventional

Purpose:

Treatment

Allocation:

Randomized controlled trial

Masking:

Double Blind

Control group:

Active

Study design:

Parallel

Phase:

Target sample size:

180

Contact for public queries

Section to complete information about Email address, telephone number and postal address of the contact who will respond to general queries, including information about current recruitment status

First Name:

Iglermys

Last Name:

Figueroa Garcia

Specialty:

First degree specialist in Allergy and Integral General Medicine

Affiliation:

Surgical Clinical Hospital “Hermanos Ameijeiras”.

Postal Address:

701San Lazaro ave, corner to Belascoain.

City:

Havana

País:

Cuba

Zip Code:

10300

Telephone:

+53-78761898; +53-78761899

Email :

iglermis@infomed.sld.cu [1]

Contact for scientific queries

Section to complete information about Email address, telephone number and postal address of the contact who will respond to scientific queries.

First Name:

Mary

Middle Name:

Carmen

Last Name:

Reyes Zamora

Specialty:

Frist Degree Specialist in Immunology, Master in Clinical Trials

Affiliation:

National Center of Bioproducts (BioCen), Group of Clinical Trials.

Postal Address:

Road to Beltran Km 1 ½, Bejucal

City:

Mayabeque

País:

Cuba

Zip Code:

13050, Box 6048

Telephone:

+53-47682441, +53-4706682201 al 07, extensión: 1145

Email :

mcarmen.reyes@biocen.cu [2]

Registration and Update

Section to complete information about the name of Primary Registry, date of registration and the unique ID number assigned by the registry (RPCEC).

Primary registry:

RPCEC

Unique ID number:

RPCEC00000298

Date of Registration in Primary Registry:

14/02/2019

Record Verification Date:

2020/04/15

Next update date:

2021/04/15

Link to the spanish version:

Click here [3]