Combined sublingual immunotherapy VALERGEN-DP and VALERGEN-BT-Asthma-Adults-Phase II

• Register: RPCEC
• Last refreshed on: 29 April 2024
• Main ID: RPCEC00000240
• Date of registration: 17/02/2017
• Prospective Registration: Yes
• Primary sponsor: National Center of Bioproducts (BIOCEN)
• Public title: Combined sublingual immunotherapy VALERGEN-DP and VALERGEN-BT-Asthma-Adults-Phase II
• 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).
• Date of first enrolment: 07/02/2019
• Target sample size: 120
• Recruitment status: Recruiting
• URL: https://rpcec.sld.cu/en/trials/RPCEC00000240-En
• Study type: Interventional
• Study design: Allocation: Randomized controlled trial. Masking: Double Blind. Control group: Active. Assignment: Parallel. Purpose: Treatment
• Phase: 2

Countries of recruitment

Cuba

Contacts

• Name: Raúl Lázaro Castro Almarales
• Affiliation: National Center of Bioproducts (BIOCEN), Group of Clinical Trials.

• Name: María de los Ángeles Tamayo Gutierrez
• Affiliation: Calixto García Hospital

Key inclusion & exclusion criteria

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.

Age minimum: 18 years
Age maximum: 45 years
Gender: Male/Female

Health Condition(s) or Problem(s) studied

Immune System Diseases

Lung Diseases, Obstructive

Respiratory Hypersensitivity

Bronchial Diseases

Lung Diseases

Respiratory Tract Diseases

Hypersensitivity

Hypersensitivity, Immediate

Asthma

Environmental Illness

Intervention(s)

Desensitization, Immunologic

Administration, Sublingual

Dermatophagoides pteronyssinus

Sublingual Immunotherapy

Immunotherapy, Active

Pyroglyphidae

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

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 + place

Placebos

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.

Secondary Outcome(s)

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.

Secondary ID(s)

GEC2017DPBT017

Source(s) of Monetary Support

National Center of Bioproducts (BIOCEN)Ministry of Public Health (MINSAP)

Secondary Sponsor(s)

Not applicable