Demonstration of Equivalence and Early Onset of a Novel Anti-allergic Nasal Spray Compared to Marketed Nasal Spray

NCT03755557 | Completed Phase 3

• 2 other identifiers: BDS_18_012018-001324-19
• Study Type: interventional
• Target: 82
• Locations: 1 country
• Sites: 1

Brief Summary

Intranasal corticosteroids are accepted as safe and effective first-line therapy for allergic rhinitis, especially in treatment of persistent symptoms. Budesonide, a non-halogenic glucocorticoid, is widely used in the management of inflammatory mucosal diseases like chronic obstructive pulmonary disease, asthma and allergic rhinitis. It is a highly fat-soluble substance with low water solubility and is presented as dispersion in marketed nasal sprays, like Rhinocort aqua 64. The maximum therapeutic efficacy of Rhinocort aqua is obtained after an application period of 7 to 14 days. In Budesolv, the solubility of budesonide is considerably increased suggesting that the same therapeutic efficacy can be reached with a lower dose. Better bioavailability of the dissolved drug promise an earlier onset of therapeutic efficacy. The current trial is undertaken to demonstrate these two effects. Subjects suffering from grass pollen allergic rhinitis will be challenged with grass pollen in a challenge chamber. Allergic subjects will be treated with two actuations (50 μl) of respective study treatment into each nostril once daily for 8 days. The total daily budesonide dose will be 40 μg per subject for Budesolv 10 and 256 μg per subject for Rhinocort® aqua 64. The primary objective of the study is to show non-inferiority of Budesolv 10 to Rhinocort® aqua 64. On day 8 grass pollen allergic patients will be challenged with grass pollen over a period of 6 hours and subjective nasal symptoms (congestion, sneezing, itching, rhinorrhea) as well as objective symptoms (nasal airflow, nasal secretion) will be assessed every 15 minutes. The second objective of the trial is to demonstrate an early on-set of therapeutic efficacy of Budesolv 10 compared to Rhinocort aqua. On day 1, grass pollen allergic patients will be challenged with grass pollen allergen in the challenge chamber over a period of 6 hours. After 1 hour 45 minutes, patients will receive their first dosage of the respective nasal spray treatment. During the 6 hour grass pollen challenge, subjective and objective endpoints will be measured every 15 minutes. To eliminate an individual bias based on expectations, the effect and onset of action is also compared to the effects of a suitable placebo. The same set of study participants will receive all three interventions in three consecutive treatment periods.

Conditions

Allergic Rhinitis; Allergic Conjunctivitis; Hayfever

Keywords

budesonide; allergic rhinitis; allergic rhinoconjuntivitis; allergen exposure chamber; onset of action; therapeutic equivalence; total nasal symptom score; hayfever; glucocorticosteroids; nasal congestion; Vienna Challenge Chamber; Carragelose; Carrageenan; Iota-Carrageenan

Outcome Measures

Primary Outcomes (1)

• Total Nasal Symptom Score

  subjective compound score evaluating "nasal congestion", "rhinorrhea", "itchy nose" and "sneezing" from "0" (absent) to "3" (severe). The sum of sub-scores is reported as total nasal symptom score (0 - 12)

  2 - 6 hours of allergen challenge

Secondary Outcomes (4)

• Total Ocular Symptom Score

  2 - 6 hours of allergen challenge

• Total Asthma Symptom Score

  2 - 6 hours of allergen challenge

• Nasal airflow

  0 - 6 hours of allergen challenge

• Nasal secretion

  0 - 6 hours of allergen challenge

Study Arms (3)

Placebo

PLACEBO COMPARATOR

Application of a placebo nasal spray once daily for 8 days Nasal Sprays

Other: Placebo

Rhinocort

ACTIVE COMPARATOR

Nasal Sprays Application of "Rhinocort Aqua 64 micrograms, nasal spray" once daily for 8 days. Daily dosage 256 µg/d

Drug: Rhinocort

Budesolv

EXPERIMENTAL

Application of a Budesolv 10 micrograms, nasal spray once daily for 8 days. Daily dosage 40 µg/d Nasal Sprays

Drug: Budesolv

Interventions

Rhinocort DRUG

Application of a nasal spray

Also known as: Budesonide

Rhinocort

Budesolv DRUG

Application of a nasal spray

Also known as: Budesonide

Budesolv

Placebo OTHER

Application of a nasal spray

Also known as: buffered saline

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent obtained before any trial related procedures are performed
• Healthy male or female subjects aged 18 years or older
• Female subjects of child-bearing potential must have a negative pregnancy test and be willing to practice appropriate contraceptive methods until the end of treatment visit
• A documented clinically relevant allergic history of moderate to severe SAR to grass pollen for the previous two years
• Subjects exhibit a moderate to severe response to approximately 1500 grass pollen grains/m3 within the first 2 hours in the Vienna Challenge Chamber, which is defined as total nasal symptom score (TNSS) of at least 6 (out of 12) using standard VCC grass pollen allergen mixture. Nasal symptom score is the sum of "nasal congestion", "rhinorrhea", "itchy nose" and "sneezing", each of which have been scored on a categorical scale from 0 to 3.
• Positive Skin Prick Test (SPT) response (wheal diameter at least 3 mm larger than diluent control) to grass pollen SPT solutions (standard Allergopharma) at screening or within the last 6 months prior to study start.
• Positive serum specific IgE against recombinant major allergen components of the used grass pollen (specific CAP IgE ≥0.70 kU/L) at screening or within the last 6 months prior to study start.
• Patients with a body weight of ≥ 50kg and a body mass index within the range of 19-30kg/m2.
• Non-smoking subjects (smoked \<10 packs years in their lifetime and had not smoked in the last 6 months)
• Asthma patients only if the asthma condition is mild or intermittent, and if those are not treated with steroids
• Subject has a forced expiratory volume in 1 second (FEV1) of at least 80% of predicted value (ECCS) at the screening.
• Subject is capable of understanding the study procedures and potential risks associated with the study, and voluntarily agrees to participate by giving written informed consent.
• Subject is able to adhere to dose and visit schedules.
• Subject is able to read, understand and complete questionnaires and diaries.

You may not qualify if:

• Pregnant, lactating or sexually active women with childbearing potential who are not using a medically accepted birth control method (pregnancy to be controlled by a pregnancy dipstick test).
• A clinical history of uncontrolled asthma within 3 months prior to screening.
• Subjects with asthma requiring treatment with inhaled corticosteroids on a regular basis judged by the investigator.
• Previous successful immunotherapy to grass pollen, a grass pollen allergen or a cross-reacting allergen within the past 3 years.
• Ongoing treatment with any allergen-specific immunotherapy product.
• Subjects with a current oral candidiasis infection or treatment for oral candidiasis during the last 30 days before starting the study.
• Subjects with history of tuberculosis.
• Subjects with any fungal/viral/bacterial respiratory or systemic infections during the last 30 days.
• Symptoms of or treatment for upper respiratory tract infection, acute sinusitis, acute otitis media or other relevant infectious process at randomization.
• Clinically relevant nasal polyps, medical history of paranasal sinus surgery and/or medical history of surgery of nasal turbinates judged by the investigator.
• Subjects with glaucoma or a family history of glaucoma.
• Subjects using any ophthalmic steroids during the last 30 days.
• Subjects treated with nasal, inhaled or systemic steroids during the last 30 days.
• History of anaphylaxis with cardiorespiratory symptoms (immunotherapy, exercise induced, food allergy, drugs or an idiopathic reaction).
• Any clinically relevant chronic disease judged by the investigator.

Sponsors & Collaborators

• Marinomed Biotech AG: lead

Study Sites (1)

Vienna Challenge Chamber

Vienna, 1140, Austria

Location

Related Publications (1)

• Murdoch RD, Bareille P, Ignar D, Miller SR, Gupta A, Boardley R, Zieglmayer P, Zieglmayer R, Lemel P, Horak F. The improved efficacy of a fixed-dose combination of fluticasone furoate and levocabastine relative to the individual components in the treatment of allergic rhinitis. Clin Exp Allergy. 2015 Aug;45(8):1346-55. doi: 10.1111/cea.12556.

  PMID: 25900517 BACKGROUND

MeSH Terms

Conditions

Rhinitis, Allergic; Conjunctivitis, Allergic; Rhinitis, Allergic, Seasonal; Nasal Obstruction

Interventions

Budesonide

Condition Hierarchy (Ancestors)

Rhinitis; Nose Diseases; Respiratory Tract Diseases; Respiratory Hypersensitivity; Otorhinolaryngologic Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Conjunctivitis; Conjunctival Diseases; Eye Diseases; Airway Obstruction; Respiratory Insufficiency; Respiration Disorders

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Eva E Prieschl-Grassauer, PhD

  Marinomed Biotech AG

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The visual aspects of the three treatment arms are identical. Identification of the treatment is achieved via a randomization code.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 3-way crossover, randomized, prospective, placebo-controlled, double blinded study in a validated allergen exposure chamber setting using grass pollen allergen

Study Record Dates

• First Submitted: November 21, 2018
• First Posted: November 28, 2018
• Study Start: November 19, 2018
• Primary Completion: April 5, 2019
• Study Completion: April 5, 2019
• Last Updated: October 12, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)