Overview
Sponsor-declared trial summary
Phase
Therapeutic exploratory (Phase II)
Status
Ended
Participants planned
317
Countries
1
Sites
4
Dry Eye
To evaluate the efficacy of 5 mcg/mL and 10 mcg/mL concentrations of the new formulation of rhNGF ophthalmic solution versus vehicle, in order to demonstrate superiority of at least one of the concentrations over vehicle in the improvement of ocular symptoms of dry eye in patients with dry eye disease (DED).
Key facts
- Sponsor
- Dompe' Farmaceutici S.p.A.
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Eye Diseases [C11]
- Trial duration
- 17 May 2024 → 4 Dec 2024
- Decision date (initial)
- 2024-04-12
- Transition trial
- No
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- Yes
- Funding sources
- Dompé farmaceutici S.p.A.
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Efficacy, Others, Safety
To evaluate the efficacy of 5 mcg/mL and 10 mcg/mL concentrations of the new formulation of rhNGF ophthalmic solution versus vehicle, in order to demonstrate superiority of at least one of the concentrations over vehicle in the improvement of ocular symptoms of dry eye in patients with dry eye disease (DED).
Secondary objectives 8
- To evaluate the efficacy of the new formulation of rhNGF ophthalmic solution in improving reflex tear production as compared to vehicle
- To evaluate the efficacy of the new formulation of rhNGF ophthalmic solution in improving tear film stability as compared to vehicle
- To evaluate the efficacy of the new formulation of rhNGF ophthalmic solution in improving ocular surface integrity (corneal and conjunctival epitheliopathy) as compared to vehicle
- To evaluate the efficacy of the new formulation of rhNGF ophthalmic solution in improving best corrected distance visual acuity (BCDVA) as compared to vehicle
- To evaluate the efficacy of the new formulation of rhNGF ophthalmic solution in improving associated symptoms of dry eye as compared to vehicle
- To evaluate the efficacy of the new formulation of rhNGF ophthalmic solution in improving quality of life as compared to vehicle
- To evaluate the safety of the new formulation of rhNGF ophthalmic solution
- To evaluate the tolerability of the new formulation of rhNGF ophthalmic solution
Conditions and MedDRA coding
Dry Eye
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 21.1 | PT | 10013774 | Dry eye | 100000004853 |
Study design 3 periods
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | Screening & Run-In period (day -12±2, Visit 1 to day 1 Visit 2) Procedures for inclusion will be performed at both Visit 1 (Screening) and Visit 2 (Baseline).
At Visit 1, eligible patients will be instructed to discontinue all topical ophthalmic medications and during the Run-In period they will only be allowed to use Study Product (vehicle) ophthalmic solution provided by the Sponsor.
The first eye drop of the Study Product (vehicle) will be applied, in both eyes of patients, at the site by the investigator during Visit 1. Patients will be instructed on how to prepare the Study Product (vehicle) daily at home and then how to self-administer one drop 3 times a day in both eyes.
A Patient Diary for the Run-In phase will be supplied to the patient. Investigators will document the first administration of the Study Product (vehicle) in the patient’s medical record following Visit 1 to confirm the first administration of the Study Product (vehicle).
|
Not Applicable | Double | [{"id":74053,"code":1,"name":"Subject"},{"id":74049,"code":5,"name":"Carer"},{"id":74050,"code":4,"name":"Analyst"},{"id":74052,"code":3,"name":"Monitor"},{"id":74051,"code":2,"name":"Investigator"}] | Run-In period: The first eye drop of the Study Product (vehicle) will be applied, in both eyes of patients, at the site by the investigator during Visit 1. Patients will be instructed on how to prepare the Study Product (vehicle) daily at home and then how to self-administer one drop 3 times a day in both eyes. No topical treatment allowed except for the Study Product vehicle ophthalmic solution provided by the Sponsor, 3 times a day, at approx. 6-hour intervals, in both eyes. |
| 2 | Treatment Period (day 1 Baseline Visit 2 to week 4, day 28 ± 1 Visit 4) The treatment period will start at Baseline visit (Visit 2, day 1) and the IMP will be administered as an eye drops solution to be prepared daily and administered by the patient TID at approximately 6-h intervals in both eyes for a treatment period of 4 weeks. During the 4 weeks of masked treatment only the administration of IMP is allowed. The use (number of drops/day) of IMP will be clearly documented in a Patient Diary and in the eCRF. Different administration frequencies will be recorded and considered as protocol deviation. The treatment period will be completed at Visit 4 (day 28 ±1) and it will be followed by a 4 weeks Follow-Up period.
|
Randomised Controlled | Double | [{"id":74058,"code":1,"name":"Subject"},{"id":74059,"code":5,"name":"Carer"},{"id":74056,"code":3,"name":"Monitor"},{"id":74055,"code":4,"name":"Analyst"},{"id":74057,"code":2,"name":"Investigator"}] | rhNGF 10µg/ml TID: arm with active IMP at the dose of 10µg/ml TID rhNGF 5µg/ml TID: arm with active IMP at the dose of 5µg/ml TID Vehicle TID: arm with veihcle TID |
| 3 | Follow-up Period (EoT Visit 4 at week 4 - to EoFU -EoS Visit 5 at week 8) During this Follow-Up period patients will be requested to administer preservative free artificial tears (AT) (NIMP) provided by the Sponsor TID at 6-h interval in both eyes for a 4-week period until Visit 5 (day 56 ±2, week 8). During the 4 weeks of Follow-Up period only the administration of AT provided by the Sponsor is allowed. The use of AT will be clearly documented in a Patient Diary and in the eCRF. Different administration frequencies will be recorded and considered as protocol deviation. Any topical ophthalmic concomitant treatment initiated during the Study period (between Visit 1 and Visit 5) must be documented on the concomitant medication log and represents a protocol deviation
|
2 | None | Artificial Tears: all pat take Artificial tears provided by the sponsor |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 7
- 1. Male or female aged ≥18 years of any race/ethnicity and eye color.
- 2. A diagnosis of dry eye disease at least 6 months before enrollment (current use or recommended use of artificial tears for the treatment of dry eye).
- 3. Dry eye disease characterized by the following clinical features: a. Symptoms Assessment in Dry Eye (SANDE) questionnaire Global Score ≥50, and b. Schirmer-I test without anesthesia >2 mm and <10 mm/5 minutes, and c. Total corneal fluorescein staining grade ≥3 (NEI scale) and/or total conjunctival lissamine green staining score ≥3 assessed by the NEI grading system, and d. Fluorescein tear film break-up time (fTBUT) < 10 seconds The same eye must have fulfilled all the above criteria
- 4. Best corrected distance visual acuity (BCDVA) score on ETDRS chart of ≥0.1 decimal units (≤1.0 logMAR) in each eye at the time of study enrollment
- 5. Negative pregnancy test in females of childbearing potential.
- 6. Only patients who satisfy 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 are performed; the informed consent form signed by patients and/or legal representatives must have been approved by the IRB for the current study.
- 7. Have the ability and willingness to comply with study procedures.
Exclusion criteria 20
- 1. 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.
- 2. Evidence of an active ocular infection in either eye.
- 3. Presence of any other ocular disorder or condition requiring topical ocular medication during the entire duration of the study.
- 4. Possibility of the need for ocular surgery at the time of inclusion in the study or anticipated ocular surgery expected during the participation in the study.
- 5. History of severe systemic allergy or severe ocular allergy (including seasonal conjunctivitis, AKC, VKC) or chronic conjunctivitis and/or keratitis other than dry eye.
- 6. Ocular scarring due to irradiation, alkali burns, Stevens-Johnson syndrome and ocular cicatricial pemphigoid.
- 7. Destruction of conjunctival goblet cells such as in Vitamin A deficiency.
- 8. Severe blepharitis or obvious inflammation of the lid margin.
- 9. Intraocular inflammation defined as Tyndall score >0
- 10. Medical history of tumor malignancy in the previous 3 years
- 11. Systemic disease not stabilized within 1 month before the screening visit (eg, diabetes with glycemia out of range, thyroid malfunction) or judged by the investigator to be incompatible with the study (eg, current systemic infections) or with a condition incompatible with the frequent assessment required by the study
- 12. History of a serious adverse reaction or significant hypersensitivity to any drug or chemically related compounds or had a clinically significant allergy to drugs, foods, topical anesthetic eye drop or other local anesthetics or other materials, including ocular vital dyes, tropicamide eye drops, commercial artificial tears.
- 13. Known or suspected allergy to sesame and other seeds, tree nuts, and/or peanuts, and/or any other component of the new rhNGF formulation.
- 14. Fertile patients (ie, not surgically sterilized, or postmenopausal women for at least 1 year) are excluded from participation in the study if they do not practice abstinence from heterosexual intercourse as per usual and customary lifestyle, or are unwilling to use an acceptable form of contraception such as condom with spermicidal cream or jelly for males, or for females if they meet any one of the following conditions: a. Currently pregnant (positive urine pregnancy test at screening or baseline visits) or planning to become pregnant during the duration of the treatment phase of the clinical trial. b. Patient is breastfeeding. c. Unwilling to use birth control measures such as mechanical barrier methods (spermicide in conjunction with a barrier such as a condom or diaphragm or intrauterine device) during the entire course of and 30 days after the study treatment period, or, d. Unwilling to continue to use highly effective birth control measures such as hormonal contraceptives (oral, implanted, transdermal, or injected) during the entire course of and 30 days after the study treatment period.
- 15. 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.
- 16. Contact lenses or punctum plug use in either eye during the Run-In, treatment, and follow-up phases of the study (previous use is not an exclusion criterion but must be removed and discontinued at the screening visit).
- 17. Medical history of drug addiction or alcohol abuse (>1 drink /day for women and >2 drinks /day for men following USDA dietary Guidelines 2020-2025).
- 18. Any prior ocular surgery including but not limited to amniotic membrane transplant, refractive (PTK/LASIK/Epi-LASIK/LASEK/SMILE), palpebral, cataract surgery, trabeculectomy, vitrectomy and pan-retinal photocoagulation (PRP) within 90 days before the screening visit.
- 19. Participation in a clinical trial with a new active substance, including medical devices, during the previous 60 days.
- 20. Participation in another clinical trial study at the same time as the present study.
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- The primary efficacy endpoint is the mean change from baseline to Week 8 in symptoms of dry eye assessed by SANDE Global Score [Time Frame: week 8 (V5)].
Secondary endpoints 17
- ● Proportion of patients improving to Schirmer-I test without anesthesia ≥10mm/5min in the Study Eye [Time Frame: at week 4 (V4)]
- ● Mean change from baseline in Schirmer-I score without anesthesia in the Study Eye [Time frame: at week 4 (V4)]
- ● Mean change from baseline in total corneal fluorescein staining (NEI scale) in the Study Eye as assessed by the investigator [Time Frame: at week 4 (V4)]
- ● Mean change from baseline in Schirmer-I score without anesthesia in the Study Eye [Time frame: at week 8 (V5)]
- ● Proportion of patients improving to Schirmer-I test without anesthesia ≥10mm/5min in the Study Eye [Time Frame: at week 8 (V5)]
- ● Mean change from baseline in fluorescein tear break-up time (fTBUT)- in the Study Eye [Time Frame: at weeks 4 (V4) and 8 (V5)]
- ● Mean change from baseline in symptoms questionnaire (SANDE) scores for severity and frequency [Time Frame: at weeks 4 (V4) and 8 (V5)]
- ● Mean change from baseline in symptoms of dry eye assessed by SANDE Global Score [Time Frame: at week 4 (V4)]
- ● Mean change from baseline in total conjunctival lissamine green staining (NEI scale) in the Study eye as assessed by the investigator [Time Frame: at week 4 (V4)]
- ● Mean change from baseline in ocular pain assessed by the OPAS questionnaire’s pain scale [Time Frame: at weeks 4 (V4) and 8 (V5)]
- ● Mean change from baseline in best corrected distance visual acuity (BCDVA) [Time Frame: at weeks 4 (V4) and 8 (V5)]
- ● Mean change from baseline of QoL assessed by the OPAS questionnaire’s QoL score [Time Frame: at weeks 4 (V4) and 8 (V5)]
- ● Safety will be monitored by the incidence and frequency of Treatment-Emergent Adverse Events (TEAEs) assessed throughout the study including Run-In period.
- ● Mean change from baseline in corneal endothelial cell density in both eyes performed at sites that have a specular microscope [Time Frame: at week 8 (V5)]
- ● Change from baseline in the proportion of patients with vitritis, retinal or vitreal hemorrhages, increase in cup-to-disc ratio, retinal or posterior vitreal detachment, retinal tears, or maculopathy on dilated fundus exam (DFE) in both eyes [Time Frame: at week 8 (V5)]
- ● Mean change from baseline in bulbar conjunctival redness in both eyes (VBR 10 score) [Time Frame: at weeks 4 (V4) and 8 (V5)]
- ● Treatment discontinuation rate due to tolerability issues.
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 2
PRD10698738 · Product
- Active substance
- Cenegermin
- Pharmaceutical form
- EYE DROPS, SOLUTION
- Route of administration
- OPHTHALMIC USE
- Max daily dose
- 0.6 µg microgram(s)
- Max total dose
- 16.8 µg microgram(s)
- Max treatment duration
- 28 Day(s)
- Authorisation status
- Not Authorised
- MA holder
- DOMPÉ FARMACEUTICI SPA
- Paediatric formulation
- No
- Orphan designation
- No
PRD10698634 · Product
- Active substance
- Cenegermin
- Pharmaceutical form
- EYE DROPS, SOLUTION
- Route of administration
- OPHTHALMIC USE
- Max daily dose
- 1.2 µg microgram(s)
- Max total dose
- 33.6 µg microgram(s)
- Max treatment duration
- 28 Day(s)
- Authorisation status
- Not Authorised
- MA holder
- DOMPÉ FARMACEUTICI SPA
- Paediatric formulation
- No
- Orphan designation
- No
Placebo 2
N/A · Product
- Other product name
- N/A
- Pharmaceutical form
- N/A
- ATC code
- N/A — N/A
- Marketing authorisation
- N/A
- MA holder
- N/A
- MA country
- Iceland
- Paediatric formulation
- No
N/A · Product
- Other product name
- N/A
- Pharmaceutical form
- N/A
- ATC code
- N/A — N/A
- Marketing authorisation
- N/A
- MA holder
- N/A
- MA country
- Iceland
- Paediatric formulation
- No
Auxiliary 3
SCP138896 · ATC
- Active substance
- Fluorescein Sodium
- Substance synonyms
- FLUORESCEIN DISODIUM
- Route of administration
- OPHTHALMIC USE
- Max daily dose
- 1 Gtt drop(s)
- Max total dose
- 10 Gtt drop(s)
- Max treatment duration
- 2 Day(s)
- Authorisation status
- Authorised
- ATC code
- S01HA02 — OXYBUPROCAINE
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP15547822 · ATC
- Active substance
- Calcium Chloride
- Route of administration
- ROUTE OF ADMINISTRATION NOT APPLICABLE
- Max daily dose
- 9999999999 ml millilitre(s)
- Max total dose
- 9999999999 ml millilitre(s)
- Max treatment duration
- 999999 Day(s)
- Authorisation status
- Authorised
- ATC code
- A12CA01 — SODIUM CHLORIDE
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP149232 · ATC
- Active substance
- Tropicamide
- Route of administration
- OPHTHALMIC USE
- Max daily dose
- 2 Gtt drop(s)
- Max total dose
- 4 Gtt drop(s)
- Max treatment duration
- 2 Day(s)
- Authorisation status
- Authorised
- ATC code
- S01FA06 — TROPICAMIDE
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Dompe' Farmaceutici S.p.A.
- Sponsor organisation
- Dompe' Farmaceutici S.p.A.
- Address
- Via San Martino 12
- City
- Milan
- Postcode
- 20122
- Country
- Italy
Scientific contact point
- Organisation
- Dompe' Farmaceutici S.p.A.
- Contact name
- Marta Sacchetti, Global Head of Clinical Development Ophthalmology & Neurotrophins
Public contact point
- Organisation
- Dompe' Farmaceutici S.p.A.
- Contact name
- Flavio Mantelli, MD, PhD Chief Medical Officer
Third parties 11
| Organisation | City, country | Duties |
|---|---|---|
| Euromed Pharma Services S.r.l. ORG-100032339
|
Grezzago, Italy | Other |
| Medidata Solutions Inc. ORG-100016256
|
New York, United States | Other |
| Lsne-Leon S.L. ORG-100017708
|
Leon, Spain | Other |
| 4g Clinical LLC ORG-100042775
|
Wellesley, United States | Interactive response technologies (IRT) |
| PPD Development LP ORG-100011560
|
Wilmington, United States | On site monitoring, Code 10, Code 11, Code 12, Code 13, Code 14, Interactive response technologies (IRT), Code 5, Data management, E-data capture, Code 8, Code 9 |
| Patheon Italia S.p.A. ORG-100011736
|
Ferentino, Italy | Code 14, Other |
| Merit CRO Inc. ORG-100042167
|
Madison, United States | Other |
| Depo-pack S.r.l. ORG-100013780
|
Saronno, Italy | Other |
| Symbiosis Pharmaceutical Services Limited ORG-100018722
|
Stirling, United Kingdom | Other |
| Pharma Quality Europe S.r.l. ORG-100046604
|
Reggello, Italy | Other |
| Optymedge LLC ORG-100045359
|
Milwaukee, United States | Other |
Locations
1 EU/EEA country · 4 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Italy | Ended | 126 | 4 |
| Rest of world
United States
|
— | 191 | — |
Investigational sites
Fondazione Policlinico Universitario Campus Bio-Medico
Oftalmologia, Via Alvaro Del Portillo N 200, 00128, Rome
Multimedica S.p.A.
Clinica Oculistica, Via San Vittore 12, 20123, Milan
Azienda Ospedaliero-Universitaria Policlinico Umberto I
Organi di Senso, Viale Del Policlinico 155, 00161, Rome
Azienda Ospedaliera Universitaria Gaetano Martino Messina
UOC Oftalmologia, Via Consolare Valeria N 1, 98124, Messina
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Italy | 2024-05-17 | 2024-11-22 | 2024-05-17 | 2024-09-13 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Summary of results Art. 37(4) CTR
| Title | Submission date | Status | Type |
|---|---|---|---|
| Summary of Results NGF0123 SUM-111333
|
2025-12-16T12:18:30 | Submitted | Summary of Results |
Layperson summary Annex V
| Title | Submission date | Status | Type |
|---|---|---|---|
| Lay Person Summary of Results NGF0123 | 2025-12-16T12:19:32 | Submitted | Laypersons Summary of Results |
Documents 8 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Laypersons summary of results (for publication) | Lay Person Summary of Results NGF0123 | 1 |
| Protocol (for publication) | D1_Dompe_NGF0123_Protocol_2023-507561-26-00_Public | 3.0 |
| Protocol (for publication) | D4_Dompe_NGF0123_OPAS questionnaire_Part I_IN_EN_Public | N/A |
| Protocol (for publication) | D4_Dompe_NGF0123_SANDE questionnaire_Part I_IN_ITA_Public | N/A |
| Protocol (for publication) | D4_Dompe_NGF0123_US1696830 Topical Anesthetic Response Test_Part I_IN_ITA_Public | N/A |
| Summary of results (for publication) | Summary of Results NGF0123 | 1 |
| Synopsis of the protocol (for publication) | D1_Dompe_NGF0123_Protocol synopis_2023-507561-26-00_EN_Public | 3.0 |
| Synopsis of the protocol (for publication) | D1_Dompe_NGF0123_Protocol synopis_2023-507561-26-00_IT_Public | 3.0 |
Application history
3 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2023-12-05 | Italy | Acceptable 2024-04-09
|
2024-04-12 |
| 2 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2024-05-08 | Italy | Acceptable 2024-04-09
|
2024-05-08 |
| 3 | NON SUBSTANTIAL MODIFICATION | NSM-3 | 2024-08-02 | Italy | Acceptable 2024-04-09
|
2024-08-02 |