Subcutaneous Immunotherapy in Patients Sensitized to Dermatophagoides Pteronyssinus (DPT)

Multicentre Phase I Randomized Double Blind Placebo Controlled Study of Subcutaneous Immunotherapy in Subjects With Allergic Rhinoconjunctivitis ± Asthma Sensitised to Dermatophagoides Pteronyssinus.

Based on EMA (European Medicines Agency) new guidelines on the clinical development of products for immunotherapy for the treatment of allergic diseases the aim of this study was to assess safety and tolerability of 3 different subcutaneous immunotherapy dose escalations in patients allergic to Dermatophagoides pteronyssinus.

Study Overview

• Status: Completed
• Conditions: Allergic Rhinoconjunctivitis
• Intervention / Treatment: Biological: subcutaneous immunotherapy with DPT extract; Biological: Subcutaneous depot placebo

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 1

Contacts and Locations

Study Locations

• Spain
  • Valencia, Spain, 46009
    • Hospital la Fé
  • Vizcaya
    • Bilbao, Vizcaya, Spain, 48013
      • Hospital de Basurto

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 with allergic rhinoconjunctivitis with or without asthma against DPT during a minimum of 1 year prior to study participation.
2. Patients must sign the informed consent form.
3. Patients must be between 18 and 60 years of age.
4. Patients who obtained a prick test result greater or equal to 3 mm diameter and a specific IgE greater or equal to class 2 (CAP/PHADIA) to DPT.
5. Patients will preferably be monosensitized to DPT. In the case of polysensitized patients they can only be included if other sensitizations are caused by seasonal allergens whose pollination do not overlap with the study period.
6. Women of childbearing potential must have a negative urine pregnancy test at Screening visit/Visit 0
7. Women of childbearing potential must agree to use an appropriate contraception method during the study if they are sexually active

Exclusion Criteria:

1. Stable and continued use of medication for allergic pathology during 2 weeks prior to inclusion.
2. Patients sensitised to other perennial allergens clinically relevant and with specific IgE levels greater or equal to class 2 CAP/PHADIA.
3. Patients who received immunotherapy in the previous 5 years for DPT or for any allergen with cross reactivity or patients that are currently receiving immunotherapy for any allergen.
4. Patients with severe asthma or FEV1 minor than 70% or asthma requiring inhaled or systemic corticoid treatment at the time of study entry or within 8 weeks prior to treatment initiation.
5. Patients with: immunological, cardiac, renal or hepatic illnesses or any other medical condition that the investigator deems relevant so as to interfere with the study.
6. Patients with a previous history of anaphylaxis
7. Patients with chronic urticaria
8. Patients with unstable angina
9. Patients with uncontrolled hypertension
10. Patients with clinically significant arrythmias
11. Patients with neoplasia
12. Patients with clinically relevant malformations of the upper respiratory tract.
13. Other chronic or immunological disease that could interfere with the assessment of the investigational product or that could generate any additional risk for the patients
14. Patients who have participated in another clinical trial within 3 month prior to enrolment.
15. Patients under treatment with tricyclic antidepressives, psychotropics beta-blockers, or Angiotensin Converting Enzyme Inhibitors (ACEI)
16. Female patients who are pregnant or breast-feeding or women of childbearing potential that do not agree to use an appropriate contraception method during the study if they are sexually active, if they have not been surgically sterilised or present any other incapacity to bear
17. Patient who does not attend the visits
18. Patient's lack of collaboration or refusal to participate

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: Group A active; 6 administrations and 5 weeks duration; Vial 2: 0.1 ml, 0.2 ml and 0.5 ml at 1 week intervals; Vial 3: 0.1 ml, 0.2 ml and 0.5 ml at 1 week intervals.	Biological: subcutaneous immunotherapy with DPT extract; Increasing doses of subcutaneous immunotherapy in three different scales up to the maximum dose of 500 TSU (Treatment Standardized Units); Other Names: DPT depot vaccine
Placebo Comparator: Group A placebo; 6 administrations and 5 weeks duration; Vial 2: 0.1 ml, 0.2 ml and 0.5 ml at 1 week intervals; Vial 3: 0.1 ml, 0.2 ml and 0.5 ml at 1 week intervals.	Biological: Subcutaneous depot placebo; Increasing doses of subcutaneous depot placebo in three different scales
Experimental: group B active; 8 administrations and 7 weeks duration; Vial 1: 0.2 ml at 1 week intervals; Vial 2: 0.1 ml, 0.2 ml, 0.4 ml at 1 week intervals; Vial 3: 0.1 ml, 0.2 ml, 0.4 ml and 0.5 ml at 1 week intervals	Biological: subcutaneous immunotherapy with DPT extract; Increasing doses of subcutaneous immunotherapy in three different scales up to the maximum dose of 500 TSU (Treatment Standardized Units); Other Names: DPT depot vaccine
Placebo Comparator: Group B placebo; 8 administrations and 7 weeks duration; Vial 1: 0.2 ml at 1 week intervals; Vial 2: 0.1 ml, 0.2 ml, 0.4 ml at 1 week intervals; Vial 3: 0.1 ml, 0.2 ml, 0.4 ml and 0.5 ml at 1 week intervals	Biological: Subcutaneous depot placebo; Increasing doses of subcutaneous depot placebo in three different scales
Experimental: Group C active; 8 administrations, 2 administrations in the same day. 1 week interval between 2 doses, during 3 weeks.; Week 1: vial 2 - 2 administrations of 0.1 ml with 30 minute interval; Week 2: vial 2 - 0.2 ml and 0.3 ml with 30 minute interval; Week 3: vial 3 - 2 doses of 0.1 ml with 30 minute interval; Week 4: vial 3 - 0.2 ml and 0.3 ml with 30 minute interval	Biological: subcutaneous immunotherapy with DPT extract; Increasing doses of subcutaneous immunotherapy in three different scales up to the maximum dose of 500 TSU (Treatment Standardized Units); Other Names: DPT depot vaccine
Placebo Comparator: Group C placebo; 8 administrations, 2 administrations in the same day. 1 week interval between 2 doses, during 3 weeks.; Week 1: vial 2 - 2 administrations of 0.1 ml with 30 minute interval; Week 2: vial 2 - 0.2 ml and 0.3 ml with 30 minute interval; Week 3: vial 3 - 2 dose of 0.1 ml with 30 minute interval; Week 4: vial 3 - 0.2 ml and 0.3 ml with 30 minute interval	Biological: Subcutaneous depot placebo; Increasing doses of subcutaneous depot placebo in three different scales

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number and Seriousness of Both Local and Systemic Adverse Reactions	The primary end points were the number of ARs and the severity of local and systemic ARs (SARs) to SCIT administration. Proportions were compared between study arms. The tolerability of SCIT was evaluated by early and late local reactions (i.e., local swelling and redness) and systemic reactions after each injection (any symptoms from organs distant from the location of the injection). Reactions were classified depending on the severity and onset of the reaction, according to the EAACI classification (Alvarez-Cuesta 2006).	From informed consent signature (V0) until the end of patient participation in the study (depending on the treatment assigned between 4 and 8 weeks )

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunoglobulin Levels (IgE Specific) Active Versus Placebo	Changes on immunoglobulin level determinations (specific IgE, IgG and IgG4) from basal visit to final visit and changes in mean wheal area in prick test dose response from basal visit to final visit, active versus placebo.	Before (V0) and after treatment (depending on the treatment assigned between 4 and 8 weeks)
Immunoglobulin Levels (IgG Total) Active Versus Placebo	Changes on immunoglobulin level determinations (IgG) from basal visit to final visit and changes in mean wheal area in prick test dose response from basal visit to final visit, active versus placebo.	Before (V0) and after treatment (depending on the treatment assigned between 4 and 8 weeks)
Immunoglobulin Levels (IgG 4) Active Versus Placebo	Changes on immunoglobulin level determinations (IgG4) from basal visit to final visit and changes in mean wheal area in prick test dose response from basal visit to final visit, active versus placebo.	Before (V0) and after treatment (depending on the treatment assigned between 4 and 8 weeks)

Collaborators and Investigators

• Sponsor: Roxall Medicina España S.A
• Investigators: Principal Investigator: Mª Dolores Hernández, MD, Hospital Universitario la Fe; Principal Investigator: Ignacio Antépara, MD, Hospital de Basurto

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (Actual): July 1, 2011
• Study Completion (Actual): August 1, 2011

Study Registration Dates

• First Submitted: December 2, 2011
• First Submitted That Met QC Criteria: December 7, 2011
• First Posted (Estimate): December 9, 2011

Study Record Updates

• Last Update Posted (Actual): May 6, 2019
• Last Update Submitted That Met QC Criteria: January 29, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: Allergy; Immunotherapy; Allergic Rhinoconjunctivitis; D. pteronyssinus; house dust allergy
• Additional Relevant MeSH Terms: Immune System Diseases; Hypersensitivity, Immediate; Eye Diseases; Hypersensitivity; Conjunctival Diseases; Conjunctivitis; Conjunctivitis, Allergic; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: BIA-DPT-P1-001; 2009-016277-15 (EudraCT Number)