Therapeutic Effect of Tacrosolv in Patients With Allergic Rhinoconjunctivitis

NCT04532710 | Completed Phase 2

• 2 other identifiers: TCS_19_022019-002847-62
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief Summary

Allergic conjunctivitis is one of the most common comorbidities of allergic diseases, especially of allergic rhinitis. Rhinoconjunctivitis is an allergic condition of the nasal mucosa and the eyes. Conjunctivitis is triggered by hypersensitivity to certain pollens and other airborne allergens and causes several symptoms such as reddened eyes, itchy eyes and can cause watery eyes and a scratchy feeling in the eye. Tacrolimus is a well-known immunosuppressiv active substance which is hardly soluble in water. Within Tacrosolv, Tacrolimus is completely dissolves in aqueous solution. The effectiveness of Tacrosolv will be tested for treatment of allergic conjunctivitis. Allergic subjects will be treated with aqueous formulation of tacrolimus 'Tacrosolv 50 micrograms per milliliter, eye drops' for 8 days. On day 1 and day 8 allergic patients will be challenged with grass pollen for a period of 4 hours and subjective allergic symptoms will be assessed.

Conditions

Allergic Conjunctivitis; Allergic Rhinitis

Keywords

Conjunctivitis; Allergic rhinoconjunctivitis; Tacrolimus; Allergen exposure chamber; Total Ocular Symptom Score; Onset of action; Tacrosolv; Ocular redness; Vienna Challenge Chamber

Outcome Measures

Primary Outcomes (1)

• Total Ocular Symptom Score

  The total ocular symptom score is the sum of four eye symptoms 'red eyes', 'itchy eyes', and 'watery eyes' and 'gritty feeling' scored every 15 minutes on a categorical scale from 0 (none) to 3 (severe) on challenge day at the times described in the Time and Events Schedule

  0-4 hours of allergen challenge

Secondary Outcomes (4)

• Total nasal symptom score (TNSS)

  0-4 hours of allergen challenge

• Total respiratory symptom score (TRSS)

  0-4 hours of allergen challenge

• Nasal airflow (AAR)

  0-4 hours of allergen challenge

• change in ocular redness image score

  0-4 hours of allergen challenge

Study Arms (4)

Placebo low dose

PLACEBO COMPARATOR

Application of 2 placebo eye drops once daily for 8 days.

Drug: Eye Drops, Solution in Single-Dose Container

Tacrosolv low dose

ACTIVE COMPARATOR

Application of 1 Tacrosolv eye drop once daily for 8 days.

Drug: Eye Drops, Solution in Single-Dose Container

Placebo high dose

PLACEBO COMPARATOR

Application of 1 placebo eye drop once daily for 8 days.

Drug: Eye Drops, Solution in Single-Dose Container

Tacrosolv high dose

ACTIVE COMPARATOR

Application of 2 Tacrosolv eye drops once daily for 8 days.

Drug: Eye Drops, Solution in Single-Dose Container

Interventions

Eye Drops, Solution in Single-Dose Container DRUG

Application of eye drops

Placebo high dose; Placebo low dose; Tacrosolv high dose; Tacrosolv low dose

Eligibility Criteria

• Age: 18 Years - 65 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 to 65 years
• Female subjects of child-bearing potential must have a negative pregnancy test and be willing to practice appropriate and safe contraceptive methods until the end of treatment visit
• A documented clinically relevant allergic history of moderate to severe SAR with rhinoconjunctivitis to grass pollen for the previous two years
• Subjects exhibit a moderate to severe response to approximately 1800 grass pollen grains/m3 within the first 2 hours in the Vienna Challenge Chamber, which is defined as total ocular symptom score (TOSS) of at least 4 (out of 12) with at least one single ocular symptom scored ≥2 ("moderate") at least twice during the first two hours of the screening challenge session using standard VCC grass pollen allergen mixture. Ocular symptom score is the sum of "ocular redness", "ocular itching", "watery eyes", "gritty feeling" 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 12 months prior to study start.
• Positive serum specific IgE against recombinant major allergen components of the used grass pollen e.g. g6 (specific CAP IgE ≥0.70 kU/L) at screening or within the last 12 months prior to study start.
• Non-smoking subjects (smoked \<10 packs per year 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 and safe birth control method (pregnancy to be controlled by a pregnancy dipstick test).
• Contact lens users
• A clinical history of uncontrolled asthma within 3 months prior to screening.
• Subjects with asthma requiring treatment with inhaled or oral 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)
• Subjects with uveitis, prior chemical burn to the ocular surface, pemphigoid, Mooren's ulcer, ulcerative keratitis, bacterial/fungal/viral infection of the eye
• Subjects using any ophthalmic steroids during the last 30 days
• Subjects treated with nasal, inhaled or systemic immunosuppressants 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)

• Sladek S, Unger-Manhart N, Siegl C, Dellago H, Zieglmayer PU, Lemell P, Savli M, Zieglmayer R, Geitzenauer W, Langauer M, Prieschl-Grassauer E. Alleviation of Allergic Rhinoconjunctivitis Symptoms in Participants Treated with a 0.005% Tacrolimus Eye-Drop Solution. Clin Ophthalmol. 2024 Oct 5;18:2797-2811. doi: 10.2147/OPTH.S476163. eCollection 2024.

  PMID: 39386177 DERIVED

MeSH Terms

Conditions

Conjunctivitis, Allergic; Rhinitis, Allergic; Conjunctivitis

Interventions

Ophthalmic Solutions; Solutions

Condition Hierarchy (Ancestors)

Conjunctival Diseases; Eye Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Rhinitis; Nose Diseases; Respiratory Tract Diseases; Respiratory Hypersensitivity; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Pharmaceutical Solutions; Pharmaceutical Preparations; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses; Specialty Uses of Chemicals

Study Officials

• Eva Prieschl-Grassauer, PhD

  CSO

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized, placebo controlled, double-blind, single site trial in a validated allergen exposure chamber setting using grass pollen induced rhinoconjunctivitis.

Study Record Dates

• First Submitted: August 21, 2020
• First Posted: August 31, 2020
• Study Start: August 4, 2020
• Primary Completion: May 27, 2021
• Study Completion: May 27, 2021
• Last Updated: August 25, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)