| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Grass pollen-induced seasonal allergic rhinoconjunctivitis |
|
| E.1.1.1 | Medical condition in easily understood language |
| Allergic reaction to grass 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 dose-response of Pollinex Quattro Grass 1.0 mL in patients with grass 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 different doses of Pollinex Quattro Grass 1.0 mL in patients with grass pollen-induced rhinoconjunctivitis. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Understands the implications of trial participation, provided in local language in the
written informed consent form (ICF), and demonstrates willingness to comply with
instructions and to attend the required study visits and has signed the informed consent.
2. Male or female aged 18 to 50 years inclusive at the time of signing Informed Consent.
3. Female patients are allowed to participate in the study if they are:
a. Not of childbearing potential defined as: post-menopausal (defined as at least 12 months natural spontaneous amenorrhea, or at least 6 weeks following surgical menopause) or,
b. Naturally or surgically sterile (hysterectomy; bilateral oophorectomy; bilateral tubal ligation with surgery at least 6 weeks prior to study screening) or,
c. Non-pregnant, non-lactating with negative urinary pregnancy test at all visits leading up to randomization and who use at least one of the following effective contraceptive methods:
i. 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,
ii. Placement of an intrauterine device (IUD) or intrauterine hormone-releasing system or,
iii. Successful male sterilization 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,
iv. 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. History of moderate to severe SAR ascribed to grass (Pooideae) pollen exposure which
required anti-allergic treatment for symptom control for at least two consecutive seasons
prior to the study. (For definitions of moderate and severe see Table 2.
6. A positive SPT for grass pollen and histamine (wheals [longest diameter] ≥ 3 mm) and
negative SPT to the negative control (wheal diameter = 0 mm) at screening.
7. Grass specific IgE and Phl p 1/5-specific IgE (as documented by an ImmunoCAP or
equivalent test) class ≥ 2 at screening.
8. Forced expiratory volume (FEV) in 1 second (FEV1) ≥ 80% of predicted, with an
FEV1/Forced Vital Capacity (FVC) ratio ≥ 70%.
9. Able to observe the drug washout times listed in Table 3 “Prohibited
Medications/Therapies” (see Exclusion Criterion 16 and Section 5.10.2 - Prohibited
Medications) prior to screening (Visit 1). 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. Positive CPT at Visit 1 or 1a (TSS ≥ 6, adjusted for reference eye score), and positive
CPT at Visit 2 to the same grass allergen concentration reached at Visit 1. Note: If CPT
at Visit 2 is negative, test increasing allergen concentrations step-wise according to
procedure until positive test is achieved. If the result can be verified at a second
confirmatory CPT visit within 6-8 days of Visit 2 (i.e. Visit 2a), the patient may be
included. |
|
| E.4 | Principal exclusion criteria |
A patient will not be included in this study if one or more of the following criteria apply:
1. Pregnant or lactating patient
2. Positive SPT [wheal (longest diameter) ≥ 3 mm] at Visit 1 to:
a) Birch / Ash / House dust mites / moulds / Epithelia (see details in protocol)
3. Moderate to severe symptoms during the 3 years prior to Visit 1* to another seasonal
or perennial allergen (see details in protocol)
4. Presence of any acute or chronic ocular disorder, other than allergic conjunctivitis,
which could interfere with the evaluation of the CPT.
5. Eye surgery with past 6 months
6. History of autoimmune disease
7. History of immunological disorders or other diseases (full list in protocol) that in the opinion of the investigator may pose a safety risk or compromise the interpretation of efficacy of the study treatment.
8. Severe psychatric, psychological or neurological disorder
9. Presence of moderate to severe asthma, characterised by the requirement to use of
inhaled steroids at a daily dose budesonide >400 μg or equivalent, as defined in the
Global Initiative for Asthma (GINA) guidelines (17).
10. Emergency room visit or hospitalisation for asthma in the 12 months prior to Visit 1
or any history of a life-threatening asthma attack.
11. Presence of non-atopic rhinitis and/or rhino-sinusitis (with or without polyps).
12. Nasal surgery (details in protocol) 8 weeks prior to visit 1
13. Active tuberculosis
14. Presence of any skin conditions (skin abnormalities, tattoos etc.), which might
interfere with the interpretation of the SPT results.
15. Current diagnosis of type I diabetes. Patients with type II diabetes will only be allowed to participate at the discretion of the investigator.
16. History of allergen-SIT. Exception: A patient may be enrolled if all of the following
points apply:
a) The SIT ended at least 5 years prior to Visit 1,
b) At least one full annual course of SIT was completed, and
c) A successful effect on symptom control was observed for at least 1 pollen season after treatment.
17. Treatment with a preparation containing MPL within 6 months prior to Visit 1.
18. Any acute infection (including upper respiratory tract infections within 14 days of
Visit 2, which may pose a safety risk.
19. Clinical history of severe or life-threatening anaphylactic reactions to foods, insect
venom, exercise, drugs or idiopathic anaphylaxis, or physical exercise.
20. Clinical history of any allergy, hypersensitivity to or intolerance of the excipients of
the study medication.
21. Tyrosine metabolism disorders, especially tyrosinemia and alkaptonuria.
22. Inability to adhere to the washout periods listed in Table 3 Prohibited Medications/ Therapies below (see also Section 5.10.2 Prohibited Medications) with respect to Visit 1 and Visit 2, and to refrain from using the medications indicated from Visit 2 until after completion of Visit 8.
23. Inability to receive epinephrine therapy
24. β-blocker medication, including eye drops, for any indication
25. Current treatment with angiotensin converting enzyme (ACE) inhibitors.
26. Anti-IgE therapy, any previous or current therapy.
27. Completed or ongoing long-term treatment with tranquilisers or psychoactive drugs
28. All vaccinations administered 14 days or less prior to randomisation or any planned vaccinations during the treatment period. Emergency vaccinations can be administered at any time
29. Current or past therapy (within previous 5 years) with immunosuppressant drugs or
immunomodulatory biologics
30. Clinical history of drug or alcohol abuse which would, interfere with the patient’s ability to participate in the study
31. Participation in a clinical research trial with any investigational medicinal product within 4 weeks of Visit 1 or concomitantly with this study
32. Unwilling or unable to comply with the procedures described in this protocol
33. Personal, financial or other dependent relationship with the study site, sponsor, sponsor’s representative, or anyone who has access to the study protocol.
34. Judicial or governmental detention, detainment or imprisonment in a public institution |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary efficacy endpoint is the post-treatment TSS following CPT. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Day 81 to 89 depending on visit 2 day |
|
| E.5.2 | Secondary end point(s) |
Efficacy:
The secondary efficacy endpoints are:
1. Change from baseline to post-treatment TSS following CPT.
2. Number of additional allergen concentration steps required to elicit a positive CPT (i.e. TSS ≥ 6,
adjusted for reference eye score) post-treatment.
3. Change in total Immunoglobulin E (IgE), grass specific IgE, grass specific immunoglobulin G(IgG)4, and specific IgE/total IgE ratio between screening and post-treatment. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Day 81 to 89 depending on visit 2 day |
|
| 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 | Yes |
| 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) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| 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 | No |
| 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 | Yes |
| E.8.2.3.1 | Comparator description |
| Test of 4 different maximum doses of Pollinex Quattro Grass |
|
| E.8.2.4 | Number of treatment arms in the trial | 5 |
| 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 | 14 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 55 |
| 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 | No |
| 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 | |
| E.8.9.1 | In the Member State concerned months | 8 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 8 |
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