A multi-centre, double-blind, randomised, placebo-controlled, parallel-group study to evaluate the efficacy and safety of Birch Modified Allergen Tyrosine adsorbed + MPL in the prevention of seasonal symptoms in subjects with allergic rhinoconjunctivitis due to birch pollen - A multi-centre study of the efficacy and safety of PQBirch [PQBirch301]

Phase 1

• Conditions: Seasonal allergic rhinoconjunctivitis due to birch pollen; MedDRA version: 20.0Level: LLTClassification code 10001728Term: Allergic rhinoconjunctivitisSystem Organ Class: 100000014962; Therapeutic area: Body processes [G] - Immune system processes [G12]

• Registration Number: EUCTR2016-002781-31-AT
• Lead Sponsor: Allergy Therapeutics (UK) Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2016-11-09
• Last Update Posted: 3 September 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 562

Inclusion Criteria

1. Written informed consent available.
2. Male or female aged 18 to 60 years inclusive at the time of signing the consent form.
3. Female patients are allowed to participate in the study if they are:
i. Not of childbearing potential, defined as: post-menopausal (defined as natural spontaneous amenorrhea for at least 12 months, or at least 6 weeks following surgical menopause), or
ii. Naturally or surgically sterile (hysterectomy; bilateral oophorectomy; bilateral tubal ligation with surgery at least 6 weeks prior to study screening).
iii. Non-pregnant, non-lactating with negative urinary pregnancy test at all visits leading up to randomisation and using at least one of the following contraceptive methods:
a) Stable hormonal contraceptive for = 90 days prior to the study and for at least 7 days after the final injection. If < 90 days prior to the study, additional use of a double barrier method until 90 days are reached is required or,
b) Placement of an intrauterine device (IUD) or intrauterine hormone-releasing system or,
c) Successful male sterilisation of the sole partner (patient must verbally confirm that appropriate post-vasectomy documentation of the absence of sperm in the ejaculate was provided after the procedure) or,
d) True abstinence when in line with the preferred and usual lifestyle of the patient.
Periodic abstinence such as calendar, ovulation, symptothermal, post-ovulation methods, and withdrawal are not acceptable methods of contraception.
4. Good general health, as determined by the investigator based on a medical evaluation including medical history, physical examination and laboratory tests. A patient with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the investigator agrees that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
5. Positive history of moderate to severe seasonal allergic rhinoconjunctivitis ascribed to birch pollen exposure which required anti-allergic treatment for symptom control for at least two consecutive seasons prior to the study.
6. A positive skin prick test (SPT) for birch pollen (wheals [longest diameter] = 3 mm and histamine = 3 mm) and a negative SPT to the negative control (wheal diameter=0) at screening.
7. Birch-specific IgE class = 2 as documented by an immunoCAP test at screening.
8. Forced expiratory volume (FEV) in 1 second (FEV1) = 80 % of predicted, with an FEV1/Forced Vital Capacity (FVC) ratio = 70 %.
9. The drug washout times listed in the table Prohibited Medications/Therapies” (see Exclusion Criterion 16 and section 5.10.2 Prohibited Medications) prior to Visit 1 and Visit 2 are observed. The use of other medications will be permitted if they are not expected to interfere with the ability of the patient to participate in the study and provided they have been on a stable regimen (i.e., the same dosage and administration form) for 30 days prior to screening.
10. The patient understands the implications of trial participation, provided in local language in the written informed consent form, and demonstrates willingness to comply with instructions and to attend the required study visits.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 562
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this ag

Exclusion Criteria

1. Pregnant or lactating.
2. Positive SPT (wheal [longest diameter] = 3 mm) at V1 to:
a) Ash (Fraxinus excelsior)
b) Gras Pollen Mix. Exception: Patients with no positive case history of moderate to severe symptoms at any time during the 3 years prior to visit 1* may be enrolled.
c) House dust mites (Dermatophagoides pteronyssinus or Dermatophagoides farinae) or moulds (Alternaria alternata). Exception: Patients with no positive case history of moderate to severe symptoms at any time during the 3 years prior to V1 may be enrolled.
d) Epithelia (cat fur and dog hair). Exception: Patients with no positive case history of moderate to severe symptoms at any time during the 3 years prior to Visit1 or patients who can avoid the allergen of concern for the duration of the trial may be enrolled.
e) Mugwort (Artemisia vulgaris), English plantain (Plantago lanceolata) or Ragweed (Ambrosia elatior) with a positive case history of moderate to severe symptoms during the 3 years prior to Visit 1. Exc.: The patient can return for the treatment period after end of the relevant pollen season. Testing not required if the allergen is uncommon to the region or the allergy season is over at the time of screening or treatment.
3. Moderate to severe symptoms to another seasonal or perennial allergen not listed in exclusion criterion 2 that cannot be avoided and the symptoms of which may interfere with administration of treatment and/or impact the data collected during the BPS.
4. History of immunological disorders or other diseases that may pose a safety risk or compromise the interpretation of efficacy of the study treatment.
5. Presence of moderate to severe asthma, characterised by the requirement to use of inhaled steroids at a daily dose budesonide >400 µg or equivalent.
6. Emergency room visit or hospitalisation for asthma in the 12 months prior to Visit 1 or any history of a life-threatening asthma attack.
7. Presence of non-atopic rhinitis and/or rhino-sinusitis (with or without polyps).
8. Presence of any skin conditions which might interfere with the interpretation of the SPT results.
9. Current diagnosis of type I diabetes. Patients with type II diabetes will only be allowed to participate at the discretion of the investigator.
10. History of allergen-specific immunotherapy (SIT). Exc.: The SIT occurred > 5 years prior to Visit 1, at least one full annual course of SIT was completed, and a successful effect on symptom control was observed for at least 1 pollen season after treatment.
11. Treatment with a preparation containing MPL® within 6 months prior to Visit 1 and, with the exception of the study drug, until after completion of Visit 10/10a.
12. Any acute infection (including upper respiratory tract infections) within 14 days of Visit 2.
13. Clinical history of severe or life-threatening anaphylactic reactions to foods, insect venom, drugs, idiopathic anaphylaxis or physical exercise.
14. Clinical history of any allergy, hypersensitivity to or intolerance of the excipients of the study medication.
15. Tyrosine metabolism disorders, especially tyrosinaemia and alkaptonuria.
16. Inability to adhere to washout periods listed in table Prohib. Medications/Therapies with respect to V1 and V2 and to refrain from using the medications indicated from V2 until after completion of V10/10a except of relief medications.
17. Inability to receive epinephrine therapy.
18. Beta blocker medication, including eye drops, for any indi

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective of this study is to evaluate the efficacy of PQ Birch<br>in birch pollen-induced rhinoconjunctivitis.;Secondary Objective: The secondary objective of this study is to evaluate the safety and<br>tolerability of PQ Birch in birch pollen-induced rhinoconjunctivitis.;Primary end point(s): The primary endpoint is the total combined symptom medication score<br>(CSMS) of the rhinoconjunctivitis daily symptom score (dSS) and<br>rhinoconjunctivitis daily medication score (dMS), averaged over the peak<br>birch pollen season (BPS).