Effect of nepafenac/dexamethasone fixed dose combination vs. its individual components (nepafenac and dexamethasone monotherapies) on postoperative inflammation after cataract surgery: a randomized, multicentre, blinded-assessor, parallel-group clinical study – NE.DE.F. STUDY

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Medivis S.r.l.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Eye Diseases [C11]

Trial duration

11 May 2026 → ongoing

Decision date (initial)

2026-02-27

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Efficacy, Pharmacokinetic, Safety

Primary efficacy objective: To demonstrate the superiority of NEPA/DEXA FDC treatment compared with its components instilled alone (i.e., NEPA and DEXA) in the time to resolution of ocular inflammation after cataract surgery.

Secondary objectives 3

1. Secondary efficacy objectives: To further evaluate the efficacy of NEPA/DEXA FDC in comparison with NEPA alone and DEXA alone on: - Postoperative ocular inflammation - Ocular symptoms - Ocular pain/discomfort - Central macular thickness - Use of rescue therapy during treatment.
2. Safety and tolerability objectives: To assess the safety and tolerability of the Investigational Medicinal Products (IMPs) throughout the trial, in terms of: - Adverse events - IOP - Visual acuity - Participant’s evaluation of drug tolerability.
3. Pharmacokinetic objective (PK sub-study): To assess the Pharmacokinetics (PK) of NEPA/DEXA FDC, NEPA and DEXA in a subset of participants at selected study site(s) related to the first IMP administration.

Conditions and MedDRA coding

Postoperative inflammation after cataract surgery

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Signed written informed consent.
2. Male or female, age ≥ 40 years.
3. Scheduled routine unilateral cataract surgery to be performed via phacoemulsification and posterior chamber intraocular lens implantation after screening. Of note, patients affected by cataract in both eyes could be enrolled if scheduled to undergo unilateral cataract surgery.
4. Patients willing to interrupt the use of contact lenses for the entire duration of the trial.
5. Patients able and willing to follow all trial procedures.
6. Females of childbearing potential must have a negative urine pregnancy test (dipstick) prior to the first IMP administration, and currently use or agree to use consistently and correctly (i.e., perfect use) a highly effective method of contraception for the individual patient and her partner(s) throughout the trial and for at least one full contraceptive cycle (when applicable). Highly effective methods of contraception include the following: a) implantable progestogen-only hormone contraception associated with inhibition of ovulation; b) Intrauterine Device (IUD); c) Intrauterine Hormone-releasing System (IUS); d) combined (oestrogen- and progestogen-containing) hormonal contraception associated with inhibition of ovulation (oral; intravaginal; transdermal), provided the patient has been using that hormonal contraceptive for an adequate period of time to ensure effectiveness; e) progestogen-only hormone contraception associated with inhibition of ovulation (oral; injectable), provided the patient has been using that hormonal contraceptive for an adequate period of time to ensure effectiveness; f) vasectomized partner, provided that the partner is the sole patient’s sexual partner and the absence of sperm has been confirmed; g) bilateral tubal occlusion or tubal ligation; h) sexual abstinence, defined as refraining from heterosexual intercourse during the entire period of risk associated with the IMP (i.e., up to 24h after the end of treatment). Barrier contraceptives (i.e., diaphragm or cervical cap with spermicide and/or condoms [male or female] with or without a spermicidal agent) are not considered highly effective methods of contraception, and thus must not be used as sole method of contraception. Of note, females who are either permanently sterilized (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy), or who are postmenopausal (at least 12 months of amenorrhea following cessation of all exogenous hormonal treatment) are not considered of childbearing potential.
7. Additional criteria for randomization (to be verified at Visit 2 after surgery): The participant has undergone unilateral cataract extraction via phacoemulsification and posterior chamber intraocular lens implantation in the study eye without any additional procedures or complications that would, in the opinion of the Investigator, interfere with trial procedures or confound trial objectives.

Exclusion criteria 13

1. Ocular conditions that, at the discretion of the Investigator, may interfere with the efficacy and/or safety evaluations (e.g., uveitis, diabetic retinopathy, retinal vasculitis, pseudo-exfoliation syndrome, intra-operative floppy iris syndrome, and any preoperative sign of intraocular inflammation in either eye).
2. Patients undergoing bilateral cataract surgery at the same time.
3. Ocular surgery in the study eye (including laser surgery) in the 3 months before screening.
4. Patients under treatment with prostaglandin analogues or intravitreal injections of anti-Vascular Endothelial Growth Factor (VEGF) drugs, the latter with the last anti-VGEF injections within 3 months before surgery and/or injections scheduled during surgery or the following 2 weeks.
5. Use of topical ocular, systemic, or inhaled NSAIDs within 1 week of surgery; use of topical ocular, inhaled, or systemic corticosteroids within 15 days of surgery; use of intraocular or periocular injection of steroids within 3 months of surgery. Of note, the use of low-dose acetylsalicylic acid for cardiovascular disease prevention is allowed.
6. Systemic diseases that may have an impact on would healing and/or affect the resolution of inflammation after cataract surgery, and thus could interfere with the results of the study, as judged by the Investigator.
7. Any condition that could interfere with the correct instillation of eye drops.
8. Monocular patients.
9. BCVA < 20/80 of the contralateral eye measured through Snellen 20 feet chart, equal to 0.25 decimal.
10. Known hypersensitivity to any component of the investigational products, procedural medications, salicylates or other NSAIDs.
11. Contraindications to ocular treatment with nepafenac (Nevanac®), dexamethasone (Dexavision®) or nepafenac/dexamethasone FDC as follows: - Uncontrolled eye infections: 1) epithelial Herpes simplex keratitis (dendritic keratitis), vaccinia, varicella zoster and other viral infections of the cornea and conjunctiva; 2) fungal and acute purulent bacterial infections, including Pseudomonas and mycobacterial infections; 3) amoebic keratitis - Perforation, ulceration and injury of cornea with uncompleted epithelialization - Known corticosteroid-induced intraocular hypertension.
12. Participation in a clinical study in the last month before screening or within 5 half-lives of the Investigational Medicinal Product (IMP) used in the previous studies, whichever is longer.
13. Pregnancy or breastfeeding throughout the whole study duration.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Primary efficacy endpoint: Time to resolution of postoperative anterior chamber inflammation after cataract surgery, as defined by an anterior chamber flare score of value = 0, equal or inferior to the preoperative value.

Secondary endpoints 18

1. Secondary efficacy endpoints: • Proportion of participants with resolution (flare score value = 0, equal or inferior to the preoperative value) of postoperative anterior chamber inflammation on postoperative Day 1, 3, 5, 7, 14 and 30
2. Secondary efficacy endpoints: • Change from baseline in the anterior chamber flare score value on postoperative Day 1, 3, 5, 7, 14 and 30
3. Secondary efficacy endpoints: • Change from baseline in the anterior chamber cells score on postoperative Day 1, 3, 5, 7, 14 and 30
4. Secondary efficacy endpoints: • Proportion of participants with absence of conjunctival hyperaemia, defined as a score equal to 0 on a 4-point Likert scale (range 0-3; 0 = none, 1 = mild, 2 = moderate, 3 = severe) on postoperative Day 1, 3, 5, 7, 14 and 30, as assessed by Slit Lamp Examination (SLE)
5. Secondary efficacy endpoints: • Proportion of participants with a Total Ocular Symptoms Score (TOSS) equal to 0 on postoperative Day 1, 3, 5, 7 and 14
6. Secondary efficacy endpoints: • Proportion of participants with no ocular pain/discomfort on postoperative Day 1, 3, 5, 7 and 14, defined as a score for ocular pain/discomfort equal to 0 on a 4-point Likert scale (range 0-3; 0 = none, 1 = mild, 2 = moderate, 3 = severe)
7. Secondary efficacy endpoints: • Change from baseline of central macular thickness (central subfield) on postoperative Day 30, as assessed by Optical Coherence Tomography (OCT)
8. Secondary efficacy endpoints: • Proportion of participants with central macular thickness (central subfield) >300 microns and cystic changes on OCT on postoperative Day 30
9. Secondary efficacy endpoints: • Proportion of participants using any rescue medication during treatment
10. Safety and tolerability endpoints: • Incidence of all Adverse Events (AEs), Adverse Drug Reactions (ADRs), Serious Adverse Events (SAEs)
11. Safety and tolerability endpoints: • Frequency of discontinuation of treatment due to AEs
12. Safety and tolerability endpoints: • Changes from baseline of IOP at each study visit
13. Safety and tolerability endpoints: • Proportion of participants with a significant increase (> 6 mmHg) in IOP vs. baseline at each study visit
14. Safety and tolerability endpoints: • Changes from baseline of Best Corrected Visual Acuity (BCVA) assessed through Snellen 20 feet chart at each study visit
15. Safety and tolerability endpoints: • Proportion of participants with 20/20 BCVA (Snellen 20 feet chart) on postoperative Day 14 and 30
16. Safety and tolerability endpoints: • Participant’s assessment of ocular complaints of burning, stinging and blurred vision on postoperative Day 1, 3, 5, 7 and 14 using a 4-point Likert scale (range 0-3; 0 = none, 1 = mild, 2 = moderate, 3 = severe)
17. Safety and tolerability endpoints: • Participant’s global evaluation of IMP tolerability on postoperative Day 14 using a 5-point Likert scale (range 0-4; 0 = poor, 1 = slight, 2 = moderate, 3 = good, 4 = excellent)
18. Pharmacokinetic endpoints (PK sub-study) • AUC0-t, AUC0-∞, area under the drug concentration-time curve • Cmax, maximum plasma concentration • Tmax, time of maximum plasma concentration

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 2

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Medivis S.r.l.

Sponsor organisation

Medivis S.r.l.

Address

Via Carnazza 34c

City

Tremestieri Etneo

Postcode

95030

Country

Italy

Scientific contact point

Organisation

Medivis S.r.l.

Contact name

Melina Cro

Public contact point

Organisation

Medivis S.r.l.

Contact name

Valentina Amico

Third parties 5

Locations

1 EU/EEA country · 8 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 23 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications