Evaluation of the Efficacy and Safety of Platelet Concentrate Eye Drops Versus Hypromellose in Patients with Dry Eye Disease: A Randomized, Double-Blind Trial
- Trial ID
- 2023-507357-15-00
- Protocol
- BTIIMD-02-EC-23-OJOS
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this randomized, parallel-group, double-blind clinical trial is to evaluate the **safety** and **efficacy** of PRGF (Plasma Rich in Growth Factors) eye drops in patients with **Dry Eye Disease**. Specifically, Part A of the study aims to assess the safety of PRGF eye drops when administered four times daily over a 12-week period. This is clinically relevant as ensuring the safety of new treatments is crucial before considering their widespread use. Part B of the study seeks to determine the superiority of PRGF eye drops compared to artificial tear eye drops containing 0.3% hypromellose, also administered four times daily for 12 weeks. Establishing the superiority of PRGF eye drops could provide a more effective treatment option for patients suffering from Dry Eye Disease, potentially improving their quality of life.
Participants
The clinical trial focuses on evaluating the safety and efficacy of PRGF eye drops in patients diagnosed with **Dry Eye Disease**. The study population includes both male and female participants aged 18 years and older. Participants are required to have a history of self-reported symptoms of dry eye disease for at least three months, confirmed by a clinical diagnosis at the screening visit. The trial does not involve a vulnerable population. The sponsor has not provided information regarding the total number of participants. Selection criteria include specific clinical measures such as a tear film break-up time of 10 seconds or less and an ocular surface staining score greater than 1 on the Oxford scale. Participants must also have an OSDI test score of 23 or higher. The trial population was selected based on these criteria, ensuring that all participants have signed informed consent and are willing to attend all study visits and procedures. No specific lifestyle considerations such as diet or physical activity are highlighted in the trial details.
Plans and Procedures
This clinical trial is designed as a **randomized**, parallel-group, **double-blind** study to evaluate the efficacy and safety of PRGF eye drops in patients with **dry eye disease**. The trial will compare the investigational product, PRGF eye drops, administered four times daily for 12 weeks, against artificial tear eye drops containing 0.3% **hypromellose**. The study is categorized as a low-intervention trial, adhering to the provisions of RD 1090/2015, and is expected to conclude by January 2026, with recruitment starting in October 2024.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age (at least 18 years), a history of dry eye symptoms for a minimum of three months, and specific clinical assessments like tear film break-up time and ocular surface staining. Following the screening, participants will attend follow-up visits at 2 and 12 weeks to assess both efficacy and safety endpoints. These include the subjective evolution of symptoms using the OSDI questionnaire, changes in ocular surface staining, and global tolerance assessments by both the investigator and the patient. The end-of-study visit will coincide with the 12-week follow-up, marking the completion of the participant's involvement in the trial.
The expected duration of participant involvement is approximately 12 weeks, with conditions for early termination including the occurrence of significant adverse events or withdrawal of consent. The primary endpoints focus on the efficacy of symptom improvement and safety through adverse event monitoring, while secondary endpoints include demographic and clinical variables, changes in visual acuity, tear quantity, and intraocular pressure. The trial's design ensures rigorous assessment of the investigational product's performance compared to standard treatment, providing valuable insights into its potential benefits for patients with dry eye disease.
Treatment
The clinical trial involves the administration of **Plasma rich in growth factors** (PRGF) as the experimental treatment. This product is formulated as **eye drops** and contains the active substance **platelet concentrate**, which is a structurally diverse substance derived from blood. The eye drops are manufactured by Biotechnology Institute I Mas D S.L. and are administered via the **ophthalmic route**. The dosage regimen involves the application of 0.4 ml daily, with a maximum total dose of 33.6 ml over a treatment period of 12 weeks. The primary objective is to evaluate the safety and efficacy of PRGF in patients with dry eye disease.
As a comparator treatment, the trial utilizes **Artific 3,20 mg/ml colirio en solución**, which is also formulated as **eye drops, solution**. The active substance in this product is **hypromellose**, a polymer, and it is produced by Bausch & Lomb, S.A. The administration is via the **ophthalmic route**, with a daily dose of 0.4 ml and a maximum total dose of 33.6 ml over a 12-week period. This comparator serves to evaluate the superiority of PRGF over standard artificial tear treatments in managing dry eye disease.
Additionally, **Hidrathea 9 mg/ml colirio en solución** is used as another comparator. This product is an **eye drops, solution** containing **sodium chloride** as the active substance, a chemical compound. Manufactured by Laboratorios Thea S.A., it is administered through the **ophthalmic route**. The dosing schedule includes a daily dose of 0.4 ml, with a maximum total dose of 5.6 ml over a 2-week period. This treatment is included to provide a baseline comparison for the efficacy of PRGF in the short-term management of dry eye disease.
Efficacy
The efficacy of the investigational product in this clinical trial will be assessed through several primary and secondary endpoints. The primary efficacy endpoints include the subjective evolution of patients' symptomatology using the Ocular Surface Disease Index (OSDI) questionnaire at 12 weeks and the change in ocular surface staining at 12 weeks using the Oxford scale. These assessments will provide insights into the improvement of symptoms associated with dry eye disease.
Secondary efficacy endpoints will further evaluate the treatment's impact. These include the subjective evolution of patients' symptomatology using the OSDI questionnaire at 2 weeks, changes in ocular surface staining at 2 weeks using the Oxford scale, and changes in global pathology symptoms with respect to severity and frequency at 2 and 12 weeks using the Visual Analog Scale (VAS). Additionally, changes in best corrected visual acuity (LogMAR VA) at 2 and 12 weeks, changes in tear quantity at 2 and 12 weeks using Schirmer's test, changes in time to tear film breakage (TBUT) at 2 and 12 weeks, and intraocular pressure (IOP) at 2 and 12 weeks will be measured.
The efficacy assessments will be conducted at specified timepoints, including weeks 2 and 12, to monitor the progression and response to treatment. The use of validated scales such as the OSDI, Oxford scale, and VAS ensures the reliability and accuracy of the data collected. These tools are integral in quantifying the subjective and objective changes in symptoms and ocular health, providing a comprehensive evaluation of the treatment's efficacy in patients with dry eye disease.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Patients aged at least 18 years
- Patients with a history of self-reported DED symptoms for a minimum period of 3 months, supported by a clinical diagnosis of DED at the time of the screening visit, with the following items being met, in at least one eye: a. Tear film break-up time ≤ 10 seconds. b. Ocular surface staining > 1 on Oxford scale.
- OSDI test ≥ 23.
- Patients who have previously signed informed consent.
- Willingness to perform all study visits and procedures.
Exclusion Criteria
- Ocular conditions/diseases 1. Any ocular abnormality other than EOS that interferes with the ocular surface including: trauma, post-radiation keratitis, infectious keratitis, Stevens-Johnson syndrome, graft-versus-host disease, ocular herpes, dacryocystitis, etc. As well as known chronic diseases that clinically compromise visual function: glaucoma, macular degeneration, proliferative diabetic retinopathy, and clinically significant primary or secondary cataracts. 2. Patients in whom the implantation of punctal plugs is anticipated during the study should be excluded. However, patients with punctal plugs placed before (> 1 month) the screening visit are eligible for enrollment; however, the plugs must remain in place during the course of the study. 3. Active non-infectious ocular inflammation (e.g., uveitis, scleritis, peripheral ulcerative keratitis) at the time of screening. 4. Any ocular disease other than EOS requiring chronic topical ocular treatment during the course of the study. 5. History of severe systemic allergy or ocular allergy (including seasonal conjunctivitis) or chronic conjunctivitis/keratitis other than that associated with dry eye. 6. Use of contact lenses, nasal stimulation device (True Tear®), moisture goggles and/or amniotic membrane without sutures, during the study (prior use is not an exclusion criterion, but must be discontinued at the screening visit). 7. Any prior ocular surgery (including refractive surgery, keratoplasties, palpebral, cataract, conjunctival surgeries, corneal transplantation), if performed within 90 days prior to the screening visit. These procedures are not allowed during the course of the study. 8. Abnormal eyelid anatomy, abnormalities in the nasolacrimal drainage system or blink dysfunction in either eye affecting palpebral function. 9. Conjunctival disorders affecting tear stability, e.g. conjunctival neoplasms.
- Ocular treatments 10. Use of topical anti-inflammatory medication such as topical corticosteroids, lifitegrast, cyclosporine (e.g. Restasis®, Ikervis®, magistral formula), tacrolimus, NSAIDs, in either eye during the study (prior use is not an exclusion criterion, but these treatments should be discontinued during the course of the study). 11. Use of autologous serum or other hematic derivatives in either eye during the course of the study (prior use is not an exclusion criterion, but this treatment must be discontinued during the course of the study). 12. Use of any type of artificial tears other than those provided by the study sponsor during the course of the study.
- Systemic conditions/diseases or treatments 13. Presence of blood disorders related to platelet or coagulation alterations. 14. Patients with uncontrolled autoimmune diseases at the time of the screening visit in the study, or patients with active systemic infectious processes. Patients positive for blood-borne infectious diseases (HBV, HCV, HIV, syphilis, etc.). 15. Any changes within 30 days after the screening visit, or any anticipated changes during the course of the study, in the dosage of systemic medications that could worsen dry eye [e.g., estrogen-progesterone or other estrogen derivatives (postmenopausal women only), pilocarpine, isotretinoin, tetracycline, antihistamines, tricyclic antidepressants, anxiolytics, antimuscarinics, beta-blocking agents, phenothiazines, omega-3, systemic corticosteroids, systemic immunosuppressants, etc]. These treatments are allowed during the study, provided they remain stable during the course of the study. 16. Illness not stabilized within 30 days prior to the screening visit (e.g., diabetes with out-of-range blood glucose, thyroid malfunction, uncontrolled autoimmune disease, active systemic infections) or any that, in the investigator's judgment, is incompatible with the study. 17. Presence or history of severe systemic allergy. 18. Known hypersensitivity to any of the components of the study drugs or used in the procedures (e.g., fluorescein, lissamine green, etc.). 19. History of uncontrolled neoplastic disease within the last 5 years. 20. Pregnancy or breastfeeding at the initial visit. 21. Women of childbearing age who are not taking effective contraceptive measures, as outlined in the CTFG "Recommendations Regarding Contraception and Pregnancy Testing in Clinical Trials" V 1.1, throughout the conduct of the study treatment periods and up to 2 weeks after the study. Postmenopausal women (two years without menstruation) do not need to use any method of birth control. 22. History or presence of general systemic condition or serious ocular condition that the investigator determines may confound study results or increase risk to the patient.
- Compliance/administrative 23. History of drug addiction or alcohol abuse (more than 4 standard drinks per day) within the past 2 years. 24. Presence or history of any systemic or ocular disorder, condition or disease that could possibly interfere with the performance of the required study procedures or the interpretation of study results. 25. Participation in a clinical trial with an investigational product within the last 30 days. 26. Participation in another clinical trial at the same time as the present study.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Spain | Not Yet Recruiting | 01 Oct 2024 | 54 |
Sites & Investigators
Research sites
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 |
|---|---|---|---|---|---|---|
Hidrathea 9 mg/ml colirio en solución | Comparator | COLIRIO EN SOLUCIÓN | OPHTHALMIC USE | 0.4 | 2 | PRD320308 |
Plasma rich in growth factors | Test | EYE DROPS | OPHTHALMIC USE | 0.4 | 12 | PRD11318462 |
Artific 3,20 mg/ml colirio en solución | Comparator | COLIRIO EN SOLUCIÓN | OPHTHALMIC USE | 0.4 | 12 | PRD5834546 |