Combined sublingual immunotherapy VALERGEN-DP and VALERGEN-BT-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:

Clinical trial of combined immunotherapy con with allergenic extracts Dermatophagoides pteronyssinus (VALERGEN-DP) and Blomia tropicalis (VALERGEN-BT) by sublingual route in sensitized asthmatic adults (version 1.3).

Secondary indentifying numbers:

GEC2017DPBT017

Issuing authority of the secondary identifying numbers:

National Center of Bioproducts (BIOCEN)

Source(s) of monetary or material support:

National Center of Bioproducts (BIOCEN)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 :

21/01/2016

Reference number:

101/05.005.15.BC

Principal investigator

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

First name:

María

Midle name:

de los Ángeles

Last name:

Tamayo Gutiérrez

Medical Specialty :

1st Degree Specialist in Allergology

Affiliation:

University Hospital "General Calixto Garcia", Allergology Department

Postal address:

Universidad y J

City:

Havana

Country:

Cuba

Zip Code:

10400

Telephone:

+53-78311508

+53-78388296

Email address:

mariatamayo@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, Joaquin Albarran Hospital, Victor White Mediacejas, MD, First degree specialist in Allergology

Havana, Center of Medical Surgical Investigations (CIMEQ), Omar Herrera Barrios, MD, First degree specialist in Allergology

Havana, Clinical of 43, Omar Herrera Barrios, MD, First degree specialist in Allergology

Sancti Spíritus, Camilo Cienfuegos Maternal and Child Clinic Surgical Hospital, Niurka Martínez DíazMD, MD, First degree specialist in Allergology

Sancti Spíritus, Juan M. Martínez Puentes (Pol. Norte) University Polyclinic, Álvaro González Iglesias, MD, First degree specialist in Allergology

Sancti Spíritus, Rudelsindo García del Rijo (Pol. Sur) University Polyclinic, Matilde Iraida Morera Franco, MD, First degree specialist in Allergology

Sancti Spíritus, Manuel de Jesús Lara Cantero University Polyclinic, Adriana Albert Montero, MD, First degree specialist in Allergology

Sancti Spíritus, Antonio Ávila Valdivia University Polyclinic, Ropsalig Guerra Marzo, MD, First degree specialist in Allergology

Camagüey, Manuel Ascunce Domenech County Hospital, Osaida Calderin Marin, MD, First degree specialist in Allergology

Camagüey, Amalia Simoni Hospital, Edilberto Machado del Risco, MD, First degree specialist in Allergology

Research ethics committees:

University Hospital “General Calixto Garcia”, June 20, 2014, March 16, 2018.

Joaquin Albarran Hospital, March 18, 2018.

Center of Medical Surgical Investigations (CIMEQ), in evaluation.

Clinical of 43, April 20, 2018

Camilo Cienfuegos Maternal and Child Clinic Surgical Hospital, April 19, 2018.

Juan M. Martínez Puentes (Pol. Norte) University Polyclinic, March 3, 2018.

Rudelsindo García del Rijo (Pol. Sur) University Polyclinic, March 9, 2018.

Manuel de Jesús Lara Cantero University Polyclinic, March 20, 2018.

Antonio Ávila Valdivia University Polyclinic, March 26, 2018.

Manuel Ascunce Domenech County Hospital, March 30, 2018.

Amalia Simoni Hospital, March 27, 2018.

Recruitment status

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

Recruitment status:

Recruiting

Date of first enrollment:

07/02/2019

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):

1. Group A (experimental): VALERGEN-DP + VALERGEN-BT by sublingual route. The treatment has 2 phases: Increasing phase: Vaccination daily for 23 days and a maintenance phase: Vaccination twice a week (Monday and Friday) until 12 months. Increasing phase: Day 1 to 7: concentration of 10 UB/mL VALERGEN-DP and 10 BU / mL VALERGEN-BT. Day 8 to 14: concentration of 100 UB/mL VALERGEN-DP and 100 BU/mL VALERGEN-BT. Day 15 to 21: concentration of 1000 UB/mL VALERGEN-DP and 1000 BU/mL VALERGEN-BT. Day 22 and 23: concentration of 10000 UB/mL VALERGEN-DP and 10000 BU/mL VALERGEN BT Maintenance phase: It starts when the patient reaches the maximum tolerated dose (recommended between 600 and 2000 UB/mL). The maximum tolerated dose is “the dose at which no systemic reactions were observed grade I-IV”. For patients receiving complete the increasing phase, the maintenance dose is 2000 UB. 2. Group B (Control): VALERGEN-BT + placebo by sublingual route. The treatment has 2 phases: Increasing phase: Vaccination daily for 23 days and a maintenance phase: Vaccination twice a week (Monday and Friday) until 12 months. Increasing phase: Day 1 to 7: concentration of 10 UB/mL VALERGEN-BT and Placebo. Day 8 to 14: concentration of 100 UB/mL VALERGEN-BT and Placebo. Day 15 to 21: concentration of 1000 UB/mL VALERGEN-BT and Placebo. Day 22 and 23: concentration of 10000 UB/mL VALERGEN-BT and Placebo Maintenance phase: It starts when the patient reaches the maximum tolerated dose (recommended between 600 and 2000 UB/mL). The maximum tolerated dose is “the dose at which no systemic reactions were observed grade I-IV”. For patients receiving complete the increasing phase, the maintenance dose is 1000 UB. 3. Group C (Control): VALERGEN-DP + placebo by sublingual route. The treatment has 2 phases: Increasing phase: Vaccination daily for 23 days and a maintenance phase: Vaccination twice a week (Monday and Friday) until 12 months. Increasing phase: Day 1 to 7: concentration of 10 UB/mL VALERGEN-DP and Placebo. Day 8 to 14: concentration of 100 UB/mL VALERGEN-DP and Placebo. Day 15 to 21: concentration of 1000 UB/mL VALERGEN-DP and Placebo. Day 22 and 23: concentration of 10000 UB/mL VALERGEN-DP and Placebo. Maintenance phase: It starts when the patient reaches the maximum tolerated dose (recommended between 600 and 2000 UB/mL). The maximum tolerated dose is “the dose at which no systemic reactions were observed grade I-IV”. For patients receiving complete the increasing phase, the maintenance dose is 1000 UB.

Intervention code:

Dermatophagoides pteronyssinus

Pyroglyphidae

Sublingual Immunotherapy

Desensitization, Immunologic

Immunotherapy, Active

Administration, Sublingual

Placebos

Intervention keyword:

VALERGEN-DP, VALERGEN-BT, allergenic extract, Blomia tropicalis

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):

1. Symptom score (Dyspnea, cough, expectoration, wheeze and chest tightness using a four-digits score: 0= non symptom, 1=mild, 2 = moderate, 3 = severe). Measurement time: daily, pre-treatment and during 12 months. 2. Consumption of medications (three-digit score: 0= no use, 1= use beta-2 agonists, metilxantine, ephedrine, adrenaline, 2 = corticosteroids). Measurement time: daily, pre-treatment and during 12 months. 3. Determination of Peak Expiratory Flow-PEF (using standard meter of PEF: FERRARIS POCKETPEAK). Measurement time: twice daily, pre-treatment and during 12 months. 4. Skin reactivity: (value Ch10: relative allergen concentration causing in the patient a similar wheal to induced wheal by a HCL histamine solution (10 mg/mL= 54.3 mmol/L de Histamina base)). Measurement time: pre-treatment, 6 and 12 months. 5. Quality of life (according to AQLQ(S) Asthma Quality of Life Questionnaire: seven-digit score (1 = maxim deteriorate to 7= no deteriorate)). Measurement time: pre-treatment, 6 and 12 months.

Key secondary outcomes:

1. Respiratory function classification (Criterion according PEF and PEF Variability: normal, mild obstruction, moderate obstruction, severe obstruction). Measurement time: pre-treatment, 6 y 12 months. 2. General evaluation (based on symptom-medication score, respiratory function, skin reactivity, quality of life: Better, Equal, Worse). Measurement time: pre-treatment, 6 y 12 months. 3. Allergen-specific antibodies (Measuring serum allergen-specific antibodies IgG4 and IgE level in the patients using indirect ELISA). Measurement time: pre-treatment, 6 and 12 months. 4. Adverse events-AE (Occurrence of some AE (Yes, No), Description of the AE (Name of adverse event),According to available previous information (Unexpected, Expected), According to its localization the expected AE (World Allergy Organization Criterion: local and systemic AE (0= Nonspecific Symptoms, I= Mild systemic reactions, II= Moderate systemic reactions, III= Severe (nonlife-threatening) systemic reactions, IV= Anaphylactic shock)), Duration of the AE (Time between the start and the end of the AE), Graveness of the AE (Serious, No serious), Attitude regarding the treatment in study (Without changes, Dose modification, Temporary interruption, Definitive interruption), Result of the AE (Recovered, Improved, Persists, Sequels), Causality Relationship of the AE (1.Very likely, 2.Likely, 3.Possible, 4.Unlikely, 5.Not related, 6.Not evaluated)). Measurement time: weekly during the first month and, monthly until month 12.

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:

45 years

Inclusion criteria:

1. Asthmatic allergic patients with positive responses during the preliminary survey in the following aspects: family and personal history of atopy, clinical symptoms only triggered when exposed to dust at home, mainly indoors, when getting up in the morning or going to bed at night. 2. Skin test positive with similar diameter (difference not mayor of 2 mm) to allergenic extracts of D. pteronyssinus and B. tropicalis, VALERGEN, 20,000 BU/ml. 3. Patients included in the study will be patients clinically diagnosed as extrinsic asthmatics who, according the clinical-therapeutic identification booklet, are classified as mild or moderate persistent patients in keeping with the International Consensus on Asthma Diagnosis and Treatment (GINA). 4. Age between 18 and 45 years. 5. Any gender and skin color. 6. Patients expressing their consent in writing to participate in clinical trial.

Exclusion criteria:

1. Patients on allergenic extract immunotherapy during the two preceding years. 2. Patients classified as intermittent or severe persistent asthmatics after being interviewed. 3. Patients with a diagnosed autoimmune disease of any kind. 4. Generalized severe eczema. 5. Patients with diagnosed tumor disease. 6. Patients on beta-blocker treatment. 7. Patients with psychiatric disorders. 8. Patients not cooperating with treatment. 9. Patients who, at least one year before the study, needed immunestimulant or immunesuppressor treatment (no corticosteroids), including interferon and cyclosporine A. 10. Pregnancy and breastfeeding. 11. Adrenalin-contraindicated patients (high blood pressure). 12. Patients who, at least one year before the study, were under non-conventional treatments such as: Vimang, Aloe, ozone, banana capsules.

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:

120

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:

María

Middle Name:

de los Ángeles

Last Name:

Tamayo Gutierrez

Specialty:

1st degree specialist in Allergology

Affiliation:

Calixto García Hospital

Postal Address:

Universidad Avenue y J Street

City:

Havana

Country:

Cuba

Zip Code:

10400

Telephone:

78388296, 78311508

Email :

mariatamayo@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:

Raúl

Middle Name:

Lázaro

Last Name:

Castro Almarales

Specialty:

Second degree specialist in Allergy

Affiliation:

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

Postal Address:

Carretera Beltran Km 1 ½, Bejucal.

City:

Mayabeque

Country:

Cuba

Zip Code:

32600

Telephone:

+53 47 682201-07 ext 1145 and 1147

Email :

rcastro@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:

RPCEC00000240

Date of Registration in Primary Registry:

17/02/2017

Record Verification Date:

2022/10/14

Next update date:

2023/10/14

Link to the spanish version:

Click here [3]