| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Seasonal allergic rhinoconjunctivitis due to birch pollen |
|
| E.1.1.1 | Medical condition in easily understood language |
| Hay Fever due to birch pollen |
|
| E.1.1.2 | Therapeutic area | Body processes [G] - Immune system processes [G12] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10001728 |
| E.1.2 | Term | Allergic rhinoconjunctivitis |
| E.1.2 | System Organ Class | 100000004853 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
The primary objective of this study is to evaluate the efficacy of PQ Birch
in birch pollen-induced rhinoconjunctivitis. |
|
| E.2.2 | Secondary objectives of the trial |
The secondary objective of this study is to evaluate the safety and
tolerability of PQ Birch in birch pollen-induced rhinoconjunctivitis. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal 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.
|
|
| E.4 | Principal exclusion criteria |
1. Pregnant or lactating.
2. Positive SPT (wheal [longest diameter] ≥ 3 mm) at V1 to:
a) Ash (Fraxinus excelsior).
b) Grass 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 indication.
19.Monoamine oxidase inhibitor medication, tricyclic antidepressants, ACE inhibitors.
20.Anti-IgE therapy (e.g. Xolair), any previous or current therapy.
21.All vaccinations (incl. influenza) administered 7 days or less prior to Visit 2 or any planned vaccinations up to 1 week following the
last administration of study drug. Emergency vaccinations (e.g.tetanus due to injury) can be administered at any time.
22.Current or past therapy (within previous 5 years) with immunosuppressant drugs or immunomodulatory biologics.
23.Clinical history of drug or alcohol abuse which would, , interfere with the patient’s ability to participate in the study.
24. Participation in a clinical research trial with any investigational medicinal product within 4 weeks of V1 or concomitantly with this study.
25. Unwilling or unable to comply with the procedures described in this protocol.
26. Personal, financial or other dependent relationship (e.g. employee or immediate relative) with the study site, sponsor, sponsor’s representative, or any other individual who has access to the clinical study protocol.
27. Judicial or governmental detention, detainment or imprisonment in a public institution.
28. Prolonged periods of absence from home during the BPS (e.g. business or private travel) of greater than 3 consecutive days in one week (Monday to Sunday) or a total of 7 days during BPS.
29. Change of residence between geographical regions since last birch pollen season. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary endpoint is the total combined symptom medication score
(CSMS) of the rhinoconjunctivitis daily symptom score (dSS) and
rhinoconjunctivitis daily medication score (dMS), averaged over the peak
birch pollen season (BPS). |
|
| E.5.2 | Secondary end point(s) |
Efficacy:
1. The average rhinoconjunctivitis CSMS over the entire BPS
2. The average rhinoconjunctivitis daily symptoms scores (dSS) and dMS separately averaged over the peak and entire BPS
3. The average rhinoconjunctivitis CSMS during the BPS based on the peak placebo-score period (26)
4. The probability of well days and severe days during the peak and entire BPS
5. The change in immunological responses (total IgE, specific IgE, IgG and IgG4, specific IgE/total IgE ratio) between screening and Visit 10/10a
6. The change in quality of life as assessed by the RQLQ(s) over the entire BPS
Safety/Tolerability:
1. Frequency, severity and relationship of AEs
2. Frequency and intensity of ARCs (defined by the maximum intensity of all injection site (local) and systemic AEs experienced by a patient within a 24-hour period after any injection)
3. Frequency of premature discontinuation from treatment or study due to AEs
4. Changes in clinical laboratory values (chemistry, haematology, urinalysis) between screening and Visit 10/10a
5. Changes in vital sign parameters at all visits during the treatment period between pre-injection and post-injection |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 13 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 61 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 5 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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