E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Allergic Rhinitis and / or Rhinoconjunctivitis with or without Intermittent Asthma |
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E.1.1.1 | Medical condition in easily understood language |
Hay fever with or without asthma due to grass pollen |
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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 | 19.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10001728 |
E.1.2 | Term | Allergic rhinoconjunctivitis |
E.1.2 | System Organ Class | 100000004853 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10001705 |
E.1.2 | Term | Allergic asthma |
E.1.2 | System Organ Class | 100000004855 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10001723 |
E.1.2 | Term | Allergic rhinitis |
E.1.2 | System Organ Class | 100000004855 |
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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 |
Assessment of the effective dose range and the optimum dose of Depigoid® Phleum (vs. placebo) administered subcutaneously in adult patients with allergic rhinitis and/or rhinoconjunctivitis with or without intermittent asthma. Efficacy parameters will be assessed in an Environmental Challenge Chamber (ECC). |
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E.2.2 | Secondary objectives of the trial |
Assessment of additional efficacy parameters, safety and tolerability of 4 concentrations of Depigoid® Phleum (vs. placebo) administered subcutaneously during a treatment period of up to 20-weeks, and to gain some insight of the allergenic profile of the study patients before and after treatment with Depigoid® Phleum at different concentrations vs. placebo by component resolved diagnosis (sIgE patterns). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
A patient must meet ALL the following inclusion criteria to be considered for admission to the study:
1. Has provided appropriately signed and dated informed consent.
2. Is a male or female aged ≥ 18 years and ≤ 70 years at Visit S1.
3. Has a perception of disease activity of at least 2 on a 4-point Likert scale(moderate or severe).
4. Has a FEV1 value of > 80% of predicted normal at Visit S2.
5. Has complained about allergic rhinitis and/or rhino-conjunctivitis symptoms for at least 2 years, with or without intermittent asthma symptoms, caused by clinical sensitisation against grass pollen. The immunoglobulin E (IgE)-mediated sensitisation has to be verified by: - suggestive medical history AND - specific IgE against grass pollen using an ImmunoCAP specific IgE radioallergosorbent test (CAP-RAST) ≥ 2 AND - positive skin prick test (SPT). An SPT will be considered positive if the test results in a wheal diameter that is at least 3 mm. The wheal for negative control must be < 2 mm.
6. Total Nasal Symptom Score (TNSS) of ≥ 6 of maximum 12 points at least once during screening exposure of the patient to the allergen in the environmental challenge chamber (ECC)
7. Patients with allergic co-sensitization are allowed to enter the study: - being asymptomatic against co-allergens such as tree or weed pollen, house dust mites, cat and dog, and other country specific allergens (e.g. but not limited to Olea europaea [olive tree], Parietaria judaica [wall pellitory]), - with specific IgE CAP-RAST and SPT co-allergen, as specified below: • birch (and for Spanish patients only: olive/wall pellitory) pollen: specific IgE CAP-RAST ≤ 2 and < grass and an SPT wheal diameter < grass • other pollen co-allergen: specific IgE CAP-RAST and an SPT wheal diameter co-allergen < grass, • house dust mites: specific IgE CAP-RAST ≤ grass and an SPT wheal diameter co-allergen ≤ grass, • animal dander, only if exposed to animal: specific IgE CAP-RAST animal ≤ grass and an SPT wheal diameter co-allergen ≤ grass, (for patients who are not exposed, no CAP-RAST limit will be applied). Note: Alternatively, a currently performed (up to 1 month prior to Screening 2) negative provocation test (conjunctival or nasal) is acceptable and overrules a high CAP-RAST and/or a high SPT result for the respective co-allergen.
8. If a female is of non-childbearing potential, the patient must be postmenopausal for at least 1 year or surgically sterile (e.g., bilateral tubal ligation, bilateral oophorectomy or hysterectomy).
9. If a female is of childbearing potential, the patient must be non-lactating and non-pregnant (with a negative pregnancy test at Visit S2) and must correctly use an effective method of contraception during the study. An effective method of contraception is defined as one that results in a failure rate of less than 1% per year. The following are allowed methods of contraception when used continuously and properly: hormonal contraceptives administered by implant, by injection, or orally; complete abstinence; partner’s vasectomy if the female has not more than one partner. Barrier methods (e.g., preservatives) are only considered effective if used together with one of the above.
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E.4 | Principal exclusion criteria |
A patient will NOT be eligible for inclusion in this study if ANY of the following criteria are met:
1. Acute or chronic infectious conjunctivitis.
2. Has a history of significant clinical manifestations of allergy as a result of sensitisation against trees or weed pollen and perennial allergens (e.g., house dust mites). Patients are not allowed to enter into the study: - with typical symptoms against co-allergens such as tree or weed pollen, house dust mites, cat and dog, and other country specific allergens (e.g. but not limited to Olea europaea [olive tree], Parietaria judaica [wall pellitory], Spanish patients only), - with CAP-RAST co-allergen ≥ grass, except for animal dander if not exposed to animal.
3. Has uncontrolled / partly controlled asthma, according to Global Initiative for Asthma (GINA) Guidelines.
4. Has acute or chronic inflammatory or infectious diseases of the airways, sinuses or the conjunctiva.
5. Presence of clinically significant nasalnasal polyps
6. Anatomical deviations of the nasal Septum that significantly impair ventilation/airflow
7. Has chronic structural diseases of the lung (e.g., emphysema or bronchiectasis).
8. Has an autoimmune and/or immune deficiency.
9. Has any disease that prohibits the use of adrenaline (e.g., hyperthyroidism).
10. Has a severe uncontrolled disease that could increase the risk of the patients participating in the study, which include, but are not limited to, the following: cardiovascular insufficiency, any severe or unstable lung diseases, endocrine diseases, clinically significant renal or hepatic diseases or haematological disorders.
11. Has had active malignant disease during the previous 5 years.
12. Has a significant abnormal laboratory parameter or alteration in vital signs that could increase the risk to the study patient.
13. Has abused alcohol, drugs or medications within the past year.
14. Has a severe psychiatric, psychological or neurological disorder.
15. Has used immunotherapy against grass pollen within the last 5 years.
16. Has used systemic and/or topical treatment with β blockers within 1 week prior to Visit T1.
17. Is using any medication that may interfere with the immune system or has been using any medication which might still have an influence on the immune system at Visit S1.
18. Has used tricyclic antidepressants or monoamine oxidase inhibitors within 1 week prior to Visit S3.
19. Has used systemic corticosteroids within 3 months prior to Visit S3.
20. Has been immunised with any vaccine within 7 days prior to Visit T1.
21. Is expected to be non-compliant and/or not co-operative.
22. Has participated in another clinical study within 30 days prior to Visit T1.
23. Has already participated in this study.
24. Is an employee at the investigational centre or first degree relative or partner of the investigator.
25. Plans to donate germ cells, blood, organs or bone marrow during the course of the study.
26. Is not contractually capable.
27. Has a positive pregnancy test at Visit S2.
28. Is jurisdictionally or governmentally institutionalised
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the reduction of the Total Nasal Symptoms Score (TNSS) assessed after provocation in an Environmental Challenge Chamber (ECC) in patients with grass pollen induced allergic rhinitis after treatment with up to 6*0,5 mL of IMP (4 different doses of Depigoid Phleum and Placebo) at intervals of 4 weeks versus baseline. The difference in reduction of the TNSS between the 4 doses of Depigoid Phleum versus placebo will be calculated. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The results from the End of Study visit (Visit E1) will be compared to those at baseline (Visit S3). |
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E.5.2 | Secondary end point(s) |
Secondary efficacy endpoints will include:
• Single symptoms during ECC •Nasal secretion during ECC •Change of lung function parameters before and after the administration of the IMP
Secondary safety endpoints will include:
• Patients (%) suffering from systemic reactions (Grades 1 to 5 WAO) during the treatment period • Patients (%) suffering from local reactions during the treatment period • Patients (%) withdrawn from the study due to systemic reactions (Grades 1 to 5 WAO) during the build up phase • Patients (%) withdrawn from the study due to local reactions during the build-up phase • Patients (%) suffering from different severity levels of systemic reactions during the treatment period • Patients (%) suffering from different severity levels of local reactions during the treatment period • Patients (%) withdrawn from the study due to systemic reactions during the treatment period • Patients (%) withdrawn from the study due to local reactions during the treatment period • Change from baseline to the end of the treatment period in the clinical chemistry and haematological parameters • Physician’s overall tolerability assessment • Patient’s overall tolerability assessment
Additional exploratory endpoints will include immunology laboratory parameters: total and specific IgE, specific IgG1 and IgG4 and component resolved diagnosis.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
During the treatment period |
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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 | No |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | 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 | Yes |
E.8.2.3.1 | Comparator description |
4 doses of Depigoid Phleum |
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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 | 13 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 50 |
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
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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 | 2 |
E.8.9.1 | In the Member State concerned days | 15 |
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 | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |