Evaluation of Isocyclosporin A Eye Drop Solution Efficacy and Safety in Adult Atopic Keratoconjunctivitis: A Randomized, Double-Masked, Vehicle-Controlled Study
- Trial ID
- 2023-508907-19-00
- Protocol
- ICY0123
- Sponsor
- Dompe' Farmaceutici S.p.A.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the **efficacy** of IsoCsA (Isocyclosporin A) administered twice daily (BID) and four times daily (QID) compared to a vehicle, to demonstrate the superiority of at least one of the two dosages in improving ocular itching in adult patients with **atopic keratoconjunctivitis** (AKC). This is clinically relevant as ocular itching is a significant symptom affecting the quality of life in patients with AKC, and effective management can lead to improved patient outcomes.
Secondary objectives include:
- Evaluating the efficacy of each dosage of IsoCsA in improving symptoms such as itching, tearing, discomfort, mucous discharge, and photophobia compared to the vehicle.
- Assessing the efficacy in improving signs such as bulbar conjunctival hyperemia, tarsal conjunctival papillae, punctate keratitis, corneal neovascularization, cicatrizing conjunctivitis, and blepharitis compared to the vehicle.
- Evaluating improvements in Quality of Life (QoL) compared to the vehicle.
- Assessing post-instillation tolerability of each dosage.
- Evaluating improvements in bulbar conjunctival redness and corneal epithelial staining compared to the vehicle.
- Assessing the safety and tolerability of each dosage.
- Measuring blood concentration of CsA and IsoCsA after topical instillation.
Participants
The clinical trial focuses on adult patients diagnosed with **atopic keratoconjunctivitis (AKC)**. The study population includes both male and female participants aged 18 years and older. Participants are required to have a diagnosis of AKC in both eyes, with specific clinical characteristics such as an ocular itching VAS score of 50 or higher, and other symptoms like tarsal conjunctival papillary reaction or bulbar conjunctival hyperemia. The trial does not involve a vulnerable population. Participants must have a best corrected distance visual acuity score of +1.0 logMAR or better in both eyes. Lifestyle considerations include the allowance of stable doses of topical calcineurin inhibitors for dermatological use, provided they are not applied to the ocular surface, and stable systemic immunomodulatory treatments for atopic dermatitis. The sponsor has not provided information regarding the total number of participants in the trial.
Plans and Procedures
The clinical trial is designed as a **randomized**, double-masked, vehicle-controlled, parallel group study to evaluate the safety and efficacy of two different dosages of **Isocyclosporin A** eye drop solution in adult patients with **atopic keratoconjunctivitis** (AKC). The trial will span a total duration of 4 weeks, with an additional 2 weeks of follow-up. Participants will be randomly assigned to receive either the investigational product or a vehicle control, ensuring that neither the participants nor the investigators are aware of the treatment allocation, thus maintaining the double-masked nature of the study.
The sequence of study visits includes an initial screening visit to assess eligibility based on specific inclusion criteria, such as a diagnosis of AKC in both eyes and a visual acuity score of +1.0 logMAR or better. Following successful screening, participants will undergo a baseline visit where they will be randomized into treatment groups. Subsequent visits will occur at weeks 2, 4, and 6, with the primary endpoint being the mean change from baseline to week 4 in ocular itching score assessed by a visual analogue scale. Secondary endpoints include changes in ocular symptoms and signs, quality of life scores, and the incidence of treatment-emergent adverse events.
The expected length of participant involvement is approximately 6 weeks, encompassing the treatment and follow-up periods. Conditions that may lead to early termination from the study include non-compliance with study procedures, withdrawal of consent, or the occurrence of adverse events that necessitate discontinuation of the investigational product. The trial aims to demonstrate the superiority of at least one dosage of Isocyclosporin A over the vehicle in improving ocular itching in patients with AKC, thereby contributing valuable data to the understanding and management of this condition.
Treatment
The clinical trial involves the evaluation of **Isocyclosporin A**, an experimental medication formulated as an eye drop solution. The pharmaceutical form is specified as "EYE DROPS, SOLUTION," and the active substance is chemically identified as (3S,6S,9S,12R,15S,18S,21S,24S,30S,33S,34R)-30-ETHYL-34-[(E,2R)-HEX-4-EN-2-YL]-4,7,10,12,15,19,25,28-OCTAMETHYL-33-(METHYLAMINO)-6,9,18,24-TETRAKIS(2-METHYLPROPYL)-3,21-DI(PROPAN-2-YL)-1-OXA-4,7,10,13,16,19,22,25,28,31-DECAZACYCLOTETRATRIACONTANE-2,5,8,11,14,17,20,23,26,29,32-UNDECONE HYDROCHLORIDE, also known as Isocyclosporin A hydrochloride. The medication is administered via the ophthalmic route, with a maximum daily dose of 0.13 mg and a total maximum dose of 3.58 mg over a treatment period of 28 days. The administration frequency is specified as BID (twice daily) and QID (four times daily), and compliance is monitored through the use of devices such as a pipette, which is a Class I sterile medical device used for drug administration by drops.
The trial also includes a **Vehicle** control, which contains Isocyclosporin A at 0 mg/mL (0%). The vehicle serves as a comparator to evaluate the efficacy of the experimental medication. The pharmaceutical form and route of administration for the vehicle are not applicable, as it is used as a control substance in the study.
Additional non-experimental treatments used in the study include **Tropicamide**, **Sodium Chloride**, and **Fluorescein Sodium**. Tropicamide is administered as eye drops with a maximum daily dose of 2 drops and a total maximum dose of 4 drops over a 2-day period, via ocular use. Sodium Chloride is included in the study with a route of administration not applicable, and it is used in a form identified as PHF00017MIG. Fluorescein Sodium is also administered as eye drops with a maximum daily dose of 2 drops and a total maximum dose of 2 drops over a 4-day period, via ocular use. These substances are used as auxiliary treatments to support the study's objectives.
Efficacy
The efficacy of the investigational product, **Isocyclosporin A**, will be assessed in a clinical trial involving adult patients with Atopic Keratoconjunctivitis (AKC). The primary endpoint for evaluating efficacy is the mean change from baseline to Week 4 in ocular itching score, which will be assessed using a visual analogue scale (VAS). Secondary endpoints include the mean change from baseline in ocular symptoms such as itching, tearing, discomfort, mucous discharge, and photophobia, evaluated on a 4-point scale, as well as a composite score of these symptoms. These assessments will occur at Weeks 4 and 6.
Additional secondary endpoints include the mean change from baseline in ocular signs, such as bulbar conjunctival hyperemia and blepharitis, evaluated on a 4-point scale, and the mean change in corneal epithelial fluorescein staining using the modified Oxford scale. Quality of Life (QoL) scores will be assessed using the Standardized Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ-S) at Week 4. The trial will also monitor the incidence and frequency of treatment-emergent adverse events (TEAEs) throughout the study, as well as changes in best corrected distance visual acuity (BCDVA) and corneal endothelial cell density at selected sites by Week 6.
Data collection will be conducted at specified time points, including baseline, Week 2, Week 4, and Week 6, using validated scales and questionnaires. The trial is designed as a 4-week, Phase II, multicenter, randomized, double-masked, vehicle-controlled, parallel group study, with an additional 2 weeks of follow-up to evaluate the safety and efficacy of two different dosages of Isocyclosporin A eye drop solution compared to a vehicle control.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Male or female patients aged ≥18 years.
- Diagnosis of AKC in both eyes, with an ocular itching VAS score≥ 50 AND at least one of the following clinical characteristics in at least one eye: a. Presence of upper and/or lower tarsal conjunctival papillary reaction and/or limbal papillary reaction. b. A composite symptom score (CSyS) ≥4 (sum of the severity scores graded 0 to 3 for each of the following: itching, tearing, ocular discomfort, photophobia, and mucous discharge scored (composite symptom score range 0 to 15). c. Grade≥ 2 of superficial punctate keratitis as evaluated by corneal fluorescein staining modified Oxford scale (a seven-point ordinal scale [0, 0.5, 1, 2, 3, 4 and 5] with zero corresponding to complete clearing of the cornea). d. Bulbar conjunctival hyperemia score ≥ 1 on a 4-points scale (0-3)
- Best corrected distance visual acuity score of +1.0 logMAR or better in both eyes at the time of study enrollment
- If a female of childbearing potential, has a negative pregnancy test at both screening and baseline visit.
- Only patients who satisfied all informed consent requirements will be included in the study; the patient and/or his/her legal representative must have read, signed, and dated the informed consent document before any study-related procedures were performed; the informed consent form signed by patients and/or legal representatives must have been approved by the IEC for the current study.
- Has the ability and willingness to comply with study procedures.
- For patients with concomitant dermatologic allergic manifestations, stable doses of topical calcineurin inhibitors (e.g., topical tacrolimus or topical pimecrolimus) for dermatological use, including periocular and eyelid skin, are allowed if on stable doses for 30 days prior to Baseline (Day 1) and anticipated to stay on pre-study stable doses for the entire study period. However, they are not allowed on the ocular surface.
- Systemic immunomodulatory treatments for atopic dermatitis are allowed only if on stable doses for 30 days prior to Baseline (Day 1) and anticipated to stay on pre-study stable doses for the entire study period.
- For patients with concomitant ocular conditions other than AKC that require topical ophthalmic medications, they may be included if the medications are not topical ophthalmic antiallergic, corticosteroids or calcineurin inhibitors and the patients have been on a stable dose for at least the past 3 months, which is anticipated to remain the same for the entire duration for the entire study period.
Exclusion Criteria
- Inability to speak and understand the local language sufficiently to understand the nature of the study, to provide written informed consent, and to allow the completion of all study assessments.
- Evidence of an active ocular infection in either eye
- Intraocular inflammation defined as Tyndall score >0 in either eye.
- Known or suspected ocular malignancy (ocular surface, intraocular, ocular adnexa)
- Presence of cancer or any other systemic disease that may affect the ability to participate in the clinical study in the opinion of the investigator including basal cell carcinoma.
- Patients that are anatomically monocular.
- Systemic disease not stabilized within 1 month before the screening visit (e.g., diabetes with glycemia out of range, thyroid malfunction) or judged by the investigator to be incompatible with the study (e.g., current systemic infections) or with a condition incompatible with the frequent assessment required by the study.
- Received systemic administration of corticosteroids or immunosuppressive in the past 30 days prior to Screening visit.
- History of a serious adverse reaction or significant hypersensitivity to any drug or chemically related compounds to the Study Product or a clinically significant allergy to drugs, foods, amide local anesthetics or other materials and drugs used in this study.
- Females of childbearing potential (i.e., not surgically sterilized or postmenopausal for at least 1 year) are excluded from participation in the study if they meet any one of the following conditions: a. Are pregnant, b. Have a positive result at the urine pregnancy test (screening/baseline Day 1) c. Intend to become pregnant during the study treatment period, d. Are breastfeeding, e. Unwilling to continue to use highly effective birth control measures such as hormonal contraceptives (oral, implanted, transdermal, or injected), sexual abstinence (defined as refraining from heterosexual intercourse as usual and customary lifestyle) during the entire course of and 30 days after the study treatment period.
- Male fertile patients (i.e. not surgically sterilized by vasectomy) unwilling to use an acceptable form of contraception (male condom with spermicidal cream or jelly).
- Any concurrent medical condition that, in the judgment of the principal investigator, might interfere with the conduct of the study, confound the interpretation of the study results, or endanger the patient’s well-being.
- Use of topical ophthalmic cyclosporin A or other calcineurin inhibitors such as tacrolimus, pimecrolimus and topical ophthalmic corticosteroids in either eye in the past 2 weeks.
- Contact lenses or punctum plug use during the study (previous use is not an exclusion criterion but must be discontinued at the Screening Visit/ Visit 1).
- Diagnosis of other systemic diseases that are associated with ocular inflammation such as Sjogren’s disease, rheumatological diseases such as rheumatoid arthritis
- History of drug addiction or alcohol abuse (>1 drink /day for women and >2 drinks /day for men following USDA dietary Guidelines 2020-2025).
- Any prior ocular surgery (including cryosurgery or surgical excision of giant papillae) within 60 days before the screening visit in either eye.
- Participation in a clinical trial with a new active substance, including medical devices in the past 60 days.
- Participation in another clinical trial study at the same time as the present study
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Italy | Not Recruiting | 25 Mar 2024 | 69 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
VehicleIsocyclosporin A 0 mg/mL, 0% | Placebo | N/A | — | — | — | N/A |
Isocyclosporin A | Test | EYE DROPS, SOLUTION | OPHTHALMIC USE | 0.13 | 28 | PRD10855781 |
TROPICAMIDE | Other | PHF00075MIG | OCULAR USE | 2 | 2 | SCP149232 |
SODIUM CHLORIDE | Other | PHF00017MIG | ROUTE OF ADMINISTRATION NOT APPLICABLE | 9999999999 | 999999 | SCP15547822 |
OXYBUPROCAINE | Other | PHF00075MIG | OCULAR USE | 2 | 4 | SCP138896 |