Dose-response Study With Subcutaneous Immunotherapy of an Standardized Dermatophagoides Pteronyssinus (DPT) Extract

Phase II, Multicenter, Randomized, Double-blind Study, With Subcutaneous Immunotherapy, in Parallel Groups and Placebo-controlled, in Patients With Rhinoconjunctivitis ± Asthma Sensitized to Dermatophagoides Pteronyssinus.

As part of the registration plan of our products and after performing a Phase I study the present trial has been designed to compare the efficacy of 5 different doses of subcutaneous immunotherapy in depot presentation.

Study Overview

• Status: Completed
• Conditions: Allergic Rhinoconjunctivitis
• Intervention / Treatment: Biological: Allergovac depot; Biological: Allergovac depot; Biological: Allergovac depot; Biological: Allergovac depot; Biological: Allergovac depot; Biological: Allergovac depot

• Study Type: Interventional
• Enrollment (Actual): 150
• Phase: Phase 2

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08907
    • Hospital Universitari de Bellvitge
  • Huelva, Spain, 21005
    • Hospital Blanca Paloma
  • Santander, Spain, 39008
    • Hospital Marques de Valdecilla
  • Valencia, Spain, 46026
    • Hospital Universitari I Politecnic La Fe
  • Alicante
    • Orihuela, Alicante, Spain, 03314
      • Hospital Vega Baja
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Hospital Germans Triasl i Pujol
  • Guipuzcoa
    • Donostia-San Sebastián, Guipuzcoa, Spain, 20014
      • Hospital Donostia
  • La Coruña
    • Santiago de Compostela, La Coruña, Spain, 15706
      • Complejo Hospitalario Universitario de Santiago
  • Murcia
    • El Palmar, Murcia, Spain, 30120
      • Hospital Virgen de la Arrixaca
  • Pontevedra
    • Vigo, Pontevedra, Spain, 36024
      • Hospital Xeral de Vigo
  • Valencia
    • Manises, Valencia, Spain, 46940
      • Hospital de Manises
    • Xátiva, Valencia, Spain, 46800
      • Hospital Luis Alcañiz

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients must sign the Informed Consent Form.
2. Patients must be between 18 and 60 years of age.
3. Patients with perennial allergic rhinoconjunctivitis produced by Dermatophagoides pteronyssinus during at least 2 years prior to participating in the study. Although the pathology being studied is allergic rhinoconjunctivitis, patients who have concomitant mild or moderate asthma may be included.
4. Patients who have had a skin prick test result greater or equal to 3 mm in diameter against Dermatophagoides pteronyssinus.
5. Patients who have specific Immunoglobulin E (IgE) greater or equal to class 2 (CAP/PHADIA) to Dermatophagoides pteronyssinus.

6. Patients will preferably be monosensitized to Dermatophagoides pteronyssinus. Polysensitized patients may only be included in the study if their other sensitizations are produced by:

   • Pollens whose season period does not overlap with the study treatment or, if overlap, whose specific IgE levels are less than class 2.
   • Perennial allergens with specific IgE levels less than class 2.
   • Allergens that do not cohabit with the patient or whose environmental levels are not high enough to produce symptoms during the study period.
7. Women of child-bearing potential must have a negative urine pregnancy test at the time they begin the study.
8. Furthermore, women of child-bearing potential must agree to use adequate contraceptive methods during this study if they are sexually active.

Exclusion Criteria:

1. Patients with stable and continued use of medication to treat their allergic condition during the 2 weeks prior to their inclusion in the study.
2. Patients sensitized and with specific IgE levels greater or equal to class 2 to other perennial or seasonal allergens clinically relevant including other mites unless they are cross reactive with Dermatophagoides pteronyssinus.
3. Patients who have received immunotherapy in the 5 years prior to the study against either the allergen being tested or an allergen which is cross-reactive, or who are currently receiving immunotherapy for any other allergen.
4. Patients with severe asthma or FEV1< 70% or with asthma which requires treatment with inhaled or systemic corticoids at the time of the study or in the 8 weeks immediately prior to the onset of treatment.
5. Patients with immunological, cardiac, renal or hepatic diseases or with any other illness which the investigators deem may interfere with the study.
6. Patients with a prior history of anaphylaxis.
7. Patients with chronic urticaria.
8. Patients with moderate-severe atopic dermatitis.
9. Patients with clinically relevant malformations of the upper respiratory tract.
10. Patients who have participated in another clinical trial within 3 months prior to this study.
11. Patients being treated with tricyclic antidepressants, psychotropic drugs, beta-blockers, or angiotensin-converting enzyme inhibitors (ACEIs).
12. Women who are pregnant or breast-feeding or are of child-bearing age and who do not agree to use adequate contraception if they are sexually active and who have not demonstrated that they have been surgically sterilized or have other means of not bearing children.
13. Patients who cannot attend study visits.
14. Patients who are uncooperative or refuse to participate in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Allergovac depot. Group 1; Increasing dosages till the maintenance dose of 0.0625 SPT is reached. Afterwards, 3 maintenance doses are given at 4-weekly intervals.	Biological: Allergovac depot; Depot sterile suspension fpor subcutaneous injection Increasing concentrations to reach the following maintenance doses: Group 1: 0.25 SPT; Biological: Allergovac depot; Depot sterile suspension for subcutaneous injection. Increasing concentrations to reach the following maintenance doses: Group 2: 0.5 SPT; Biological: Allergovac depot; Depot sterile suspension for subcutaneous injection. Increasing concentrations to reach the following maintenance doses: Group 3: 1 SPT; Biological: Allergovac depot; depot sterile suspension for subcutaneous injection Increasing concentrations to reach the following maintenance doses: Group 4: 2 SPT; Biological: Allergovac depot; Depot sterile suspension for subcutaneous injection. Increasing concentrations to reach the following maintenance doses: Group 5: 4 SPT; Biological: Allergovac depot; Sterile suspension for subcutaneous injection. Same number of administration as the active groups
Experimental: Allergovac depot. Group 2; Increasing dosages till the maintenance dose of 0.125 SPT is reached. Afterwards, 3 maintenance doses are given at 4-weekly intervals.	Biological: Allergovac depot; Depot sterile suspension fpor subcutaneous injection Increasing concentrations to reach the following maintenance doses: Group 1: 0.25 SPT; Biological: Allergovac depot; Depot sterile suspension for subcutaneous injection. Increasing concentrations to reach the following maintenance doses: Group 2: 0.5 SPT; Biological: Allergovac depot; Depot sterile suspension for subcutaneous injection. Increasing concentrations to reach the following maintenance doses: Group 3: 1 SPT; Biological: Allergovac depot; depot sterile suspension for subcutaneous injection Increasing concentrations to reach the following maintenance doses: Group 4: 2 SPT; Biological: Allergovac depot; Depot sterile suspension for subcutaneous injection. Increasing concentrations to reach the following maintenance doses: Group 5: 4 SPT; Biological: Allergovac depot; Sterile suspension for subcutaneous injection. Same number of administration as the active groups
Experimental: Allergovac depot. Group 3; Increasing dosages till the maintenance dose of 0.25 SPT is reached. Afterwards, 3 maintenance doses are given at 4-weekly intervals.	Biological: Allergovac depot; Depot sterile suspension fpor subcutaneous injection Increasing concentrations to reach the following maintenance doses: Group 1: 0.25 SPT; Biological: Allergovac depot; Depot sterile suspension for subcutaneous injection. Increasing concentrations to reach the following maintenance doses: Group 2: 0.5 SPT; Biological: Allergovac depot; Depot sterile suspension for subcutaneous injection. Increasing concentrations to reach the following maintenance doses: Group 3: 1 SPT; Biological: Allergovac depot; depot sterile suspension for subcutaneous injection Increasing concentrations to reach the following maintenance doses: Group 4: 2 SPT; Biological: Allergovac depot; Depot sterile suspension for subcutaneous injection. Increasing concentrations to reach the following maintenance doses: Group 5: 4 SPT; Biological: Allergovac depot; Sterile suspension for subcutaneous injection. Same number of administration as the active groups
Experimental: Allergovac depot. Group 4; Increasing dosages till the maintenance dose of 0.5 SPT is reached. Afterwards, 3 maintenance doses are given at 4-weekly intervals.	Biological: Allergovac depot; Depot sterile suspension fpor subcutaneous injection Increasing concentrations to reach the following maintenance doses: Group 1: 0.25 SPT; Biological: Allergovac depot; Depot sterile suspension for subcutaneous injection. Increasing concentrations to reach the following maintenance doses: Group 2: 0.5 SPT; Biological: Allergovac depot; Depot sterile suspension for subcutaneous injection. Increasing concentrations to reach the following maintenance doses: Group 3: 1 SPT; Biological: Allergovac depot; depot sterile suspension for subcutaneous injection Increasing concentrations to reach the following maintenance doses: Group 4: 2 SPT; Biological: Allergovac depot; Depot sterile suspension for subcutaneous injection. Increasing concentrations to reach the following maintenance doses: Group 5: 4 SPT; Biological: Allergovac depot; Sterile suspension for subcutaneous injection. Same number of administration as the active groups
Experimental: Allergovac depot. Group 5; Increasing dosages till the maintenance dose of 0.75 SPT is reached. Afterwards, 3 maintenance doses are given at 4-weekly intervals.	Biological: Allergovac depot; Depot sterile suspension fpor subcutaneous injection Increasing concentrations to reach the following maintenance doses: Group 1: 0.25 SPT; Biological: Allergovac depot; Depot sterile suspension for subcutaneous injection. Increasing concentrations to reach the following maintenance doses: Group 2: 0.5 SPT; Biological: Allergovac depot; Depot sterile suspension for subcutaneous injection. Increasing concentrations to reach the following maintenance doses: Group 3: 1 SPT; Biological: Allergovac depot; depot sterile suspension for subcutaneous injection Increasing concentrations to reach the following maintenance doses: Group 4: 2 SPT; Biological: Allergovac depot; Depot sterile suspension for subcutaneous injection. Increasing concentrations to reach the following maintenance doses: Group 5: 4 SPT; Biological: Allergovac depot; Sterile suspension for subcutaneous injection. Same number of administration as the active groups
Placebo Comparator: Allergovac depot placebo. Group 6; The same scheme of treatment as the active groups	Biological: Allergovac depot; Depot sterile suspension fpor subcutaneous injection Increasing concentrations to reach the following maintenance doses: Group 1: 0.25 SPT; Biological: Allergovac depot; Depot sterile suspension for subcutaneous injection. Increasing concentrations to reach the following maintenance doses: Group 2: 0.5 SPT; Biological: Allergovac depot; Depot sterile suspension for subcutaneous injection. Increasing concentrations to reach the following maintenance doses: Group 3: 1 SPT; Biological: Allergovac depot; depot sterile suspension for subcutaneous injection Increasing concentrations to reach the following maintenance doses: Group 4: 2 SPT; Biological: Allergovac depot; Depot sterile suspension for subcutaneous injection. Increasing concentrations to reach the following maintenance doses: Group 5: 4 SPT; Biological: Allergovac depot; Sterile suspension for subcutaneous injection. Same number of administration as the active groups

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in nasal provocation test	Variation of the concentration of DPT extract needed to produce a positive nasal provocation test from baseline (V0) to final visit (FV). The changes will be compared among groups (including the placebo group).	from baseline (V0) to final visit (VF 18 weeks after randmization)

Collaborators and Investigators

• Sponsor: Roxall Medicina España S.A
• Investigators: Principal Investigator: Fernando Rodríguez, MD, Hospital Universitario Marques de Valdecilla; Principal Investigator: Ramón Lleonart, MD, Hospital Universitario Marques de Valdecilla; Principal Investigator: Albert Roger, MD, Germans Trias I Pujol Hospital; Principal Investigator: Dolores Hernández, MD, Hospital Universitario La Fe; Principal Investigator: Carmen Vidal, MD, Complejo Hospitalario Universitario de Santiago; Principal Investigator: Juan A Pagán, MD, Hospital Virgen de la Arrixaca; Principal Investigator: Carmen Marcos, MD, Hospital Xeral de Vigo; Principal Investigator: Jose A Navarro, MD, Hospital Donostia; Principal Investigator: Victoria Moreno, MD, Hospital Blanca Paloma; Principal Investigator: Luis A Navarro, MD, Hospital Luis Alcañiz; Principal Investigator: María I Peña, MD, Hospital Vega Baja; Principal Investigator: Marta Alvariño, MD, Hospital de Manises

Study record dates

Study Major Dates

• Study Start: May 1, 2012
• Primary Completion (Actual): May 1, 2013
• Study Completion (Actual): May 1, 2013

Study Registration Dates

• First Submitted: March 23, 2012
• First Submitted That Met QC Criteria: March 26, 2012
• First Posted (Estimate): March 27, 2012

Study Record Updates

• Last Update Posted (Actual): May 1, 2017
• Last Update Submitted That Met QC Criteria: April 28, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: Allergy; Immunotherapy; Allergic rhinoconjunctivitis; D. pteronyssinus; house dust allergy
• Additional Relevant MeSH Terms: Eye Diseases; Conjunctival Diseases; Conjunctivitis
• Other Study ID Numbers: BIA--DPT-P2-001; 2011-004583-30 (EudraCT Number)