Efficacy and Safety Assessment of T4020 Versus Vehicule in Patients With Chronic Neurotrophic Keratitis or Corneal Ulcer

• Sponsor: Laboratoires Thea (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01794312
• Collaborator: (none)
• Enrollment: 152
• Location: 1
• Arms: 2
• Actual Duration (Months): 58.5
• Patients Per Site Per Month: 2.6

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the efficacy and safety of T4020 versus vehicle.

Condition or Disease	Intervention/Treatment	Phase
Keratitis; Corneal Ulcer	Device: T4020; Device: Vehicle	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 152 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Efficacy and Safety Assessment of T4020 Versus Vehicule in Patients With Chronic Neurotrophic Keratitis or Corneal Ulcer
• Actual Study Start Date: Feb 1, 2013
• Actual Primary Completion Date: Dec 19, 2017
• Actual Study Completion Date: Dec 19, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: T4020 One drop every 2 days	Device: T4020
Placebo Comparator: Vehicle One drop every 2 days	Device: Vehicle

Outcome Measures

Primary Outcome Measures

1. Number of Participants With a Reduction in Neurotrophic the Keratitis/Ulcer Area on Day28 [Day 28]

   Reduction in neurotrophic ulcer/keratitis area of 50% or more

Secondary Outcome Measures

1. Number of Participants With at Least One Treatment-emergent Adverse Event [From the first visit to the final visit performed by the patient + 1 month later, assessed up to 71 days]

   With at least one TEAE

2. Best Corrected Visual Acuity [Baseline and Day 28]

   Change from baseline in far best-corrected visual acuity (LogMAR) in the pathologic eye

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 95 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Adult patients diagnosed with one chronic keratitis/corneal ulcer

• Patients who signed and dated informed consent

Exclusion Criteria:

• Patient under 18 years

• Patient with a perforated corneal ulcer OR any risk of immediate perforation of corneal ulcer.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clinical Development Director	Clermont-Ferrand		France	63000

Sponsors and Collaborators

• Laboratoires Thea

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Dec 17, 2015

More Information

Publications

None provided.

• Responsible Party: Laboratoires Thea
• ClinicalTrials.gov Identifier: NCT01794312
• Other Study ID Numbers: LT4020-PIII-12/11
• First Posted: Feb 18, 2013
• Last Update Posted: Oct 23, 2019
• Last Verified: Oct 1, 2019

• Additional relevant MeSH terms: Corneal Ulcer; Keratitis; Ulcer

Study Results

Participant Flow

Arm/Group Title	T4020	Vehicle
Arm/Group Description	One drop every 2 days	One drop every 2 days
Period Title: Overall Study
STARTED	74	78
COMPLETED	68	67
NOT COMPLETED	6	11

Baseline Characteristics

Arm/Group Title	T4020	Vehicle	Total
Arm/Group Description	One drop every 2 days	One drop every 2 days	Total of all reporting groups
Overall Participants	74	78	152
Age (Count of Participants)
<=18 years	0 0%	1 1.3%	1 0.7%
Between 18 and 65 years	37 50%	32 41%	69 45.4%
>=65 years	37 50%	45 57.7%	82 53.9%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	62.2 (17)	65.2 (17.8)	63.8 (17.4)
Sex: Female, Male (Count of Participants)
Female	40 54.1%	42 53.8%	82 53.9%
Male	34 45.9%	36 46.2%	70 46.1%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (participants) [Number]
France	16 21.6%	20 25.6%	36 23.7%
Poland	12 16.2%	14 17.9%	26 17.1%
Turkey	8 10.8%	7 9%	15 9.9%
Belgium	6 8.1%	8 10.3%	14 9.2%
Italy	7 9.5%	6 7.7%	13 8.6%
Spain	7 9.5%	5 6.4%	12 7.9%
Greece	6 8.1%	6 7.7%	12 7.9%
Switzerland	4 5.4%	4 5.1%	8 5.3%
Netherlands	4 5.4%	4 5.1%	8 5.3%
Sweden	2 2.7%	1 1.3%	3 2%
United Kingdom	1 1.4%	2 2.6%	3 2%
Austria	0 0%	1 1.3%	1 0.7%
Portugal	1 1.4%	0 0%	1 0.7%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With a Reduction in Neurotrophic the Keratitis/Ulcer Area on Day28
Description	Reduction in neurotrophic ulcer/keratitis area of 50% or more
Time Frame	Day 28

Outcome Measure Data

Analysis Population Description

Modified Intent to treat (m-ITT): All randomised patients received at least 1 IMP dose, with at least 1 baseline and 1 post-baseline efficacy assessment. For the primary outcome measure, 4 patients (2 in the T4020 and Vehicle groups) had no data for the reduction from baseline of corneal ulcer/keratitis area and were not included in this analysis

Arm/Group Title	T4020	Vehicle
Arm/Group Description	One drop every 2 days	One drop every 2 days
Measure Participants	72	76
Count of Participants [Participants]	37 50%	44 56.4%

2. Secondary Outcome

Title	Number of Participants With at Least One Treatment-emergent Adverse Event
Description	With at least one TEAE
Time Frame	From the first visit to the final visit performed by the patient + 1 month later, assessed up to 71 days

Outcome Measure Data

Analysis Population Description

Safety Set

Arm/Group Title	T4020	Vehicle
Arm/Group Description	One drop every 2 days	One drop every 2 days
Measure Participants	74	78
Count of Participants [Participants]	25 33.8%	27 34.6%

3. Secondary Outcome

Title	Best Corrected Visual Acuity
Description	Change from baseline in far best-corrected visual acuity (LogMAR) in the pathologic eye
Time Frame	Baseline and Day 28

Outcome Measure Data

Analysis Population Description

Safety set

Arm/Group Title	T4020	Vehicle
Arm/Group Description	One drop every 2 days	One drop every 2 days
Measure Participants	74	78
Mean (Standard Deviation) [LogMAR]	-0.055 (0.362)	-0.035 (0.590)

Adverse Events

Time Frame	From the first visit to the final visit performed by the patient + 1 month later, assessed up to 71 days
Arm/Group Title	T4020		Vehicle
Arm/Group Description	One drop 4 times per week		One drop 4 times per week
All Cause Mortality
	T4020		Vehicle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/74 (0%)		0/78 (0%)
Serious Adverse Events
	T4020		Vehicle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/74 (4.1%)		7/78 (9%)
Eye disorders
Ulcerative keratitis	1/74 (1.4%)	1	0/78 (0%)	0
Keratitis	1/74 (1.4%)	1	0/78 (0%)	0
Corneal neovascularisation	0/74 (0%)	0	1/78 (1.3%)	1
Uveitis	0/74 (0%)	0	1/78 (1.3%)	1
Corneal perforation	0/74 (0%)	0	1/78 (1.3%)	1
Infections and infestations
Herpes Simplex ophthalmic	1/74 (1.4%)	1	0/78 (0%)	0
Corneal infection	0/74 (0%)	0	1/78 (1.3%)	1
Keratitis bacterial	0/74 (0%)	0	1/78 (1.3%)	1
Injury, poisoning and procedural complications
Femoral neck fracture	0/74 (0%)	0	1/78 (1.3%)	1
Surgical and medical procedures
Tooth extraction	0/74 (0%)	0	1/78 (1.3%)	1
Other (Not Including Serious) Adverse Events
	T4020		Vehicle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	25/74 (33.8%)		27/78 (34.6%)
Eye disorders
Ulcerative keratitis	3/74 (4.1%)	3	4/78 (5.1%)	4
Conjuncticitis allergic, diplopia	1/74 (1.4%)	1	1/78 (1.3%)	1
Keratitis	3/74 (4.1%)	3	1/78 (1.3%)	1
Eye pain	0/74 (0%)	0	3/78 (3.8%)	3
Eye irritation	2/74 (2.7%)	2	0/78 (0%)	0
Abnormal sensation in eye	1/74 (1.4%)	1	0/78 (0%)	0
Acanthamoeba keratitis	0/74 (0%)	0	1/78 (1.3%)	1
Conjunctival hemorrhage	1/74 (1.4%)	1	0/78 (0%)	0
Conjunctivitis	0/74 (0%)	0	1/78 (1.3%)	1
Conjunctivitis allergic	1/74 (1.4%)	1	0/78 (0%)	0
Corneal epithelium defect	0/74 (0%)	0	1/78 (1.3%)	1
Corneal erosion	0/74 (0%)	0	1/78 (1.3%)	1
Corneal neovascularisation	0/74 (0%)	0	1/78 (1.3%)	1
Corneal perforation	0/74 (0%)	0	1/78 (1.3%)	1
Diplopia	0/74 (0%)	0	1/78 (1.3%)	1
Dry eye	0/74 (0%)	0	1/78 (1.3%)	1
Foreign body sensation in eyes	1/74 (1.4%)	1	0/78 (0%)	0
Iridocyclitis	1/74 (1.4%)	1	0/78 (0%)	0
Neurotrophic keratopathy	1/74 (1.4%)	1	0/78 (0%)	0
Ocular hyperaemia	0/74 (0%)	0	1/78 (1.3%)	1
Punctate keratitis	1/74 (1.4%)	1	0/78 (0%)	0
Uveitis	0/74 (0%)	0	1/78 (1.3%)	1
Vision blurred	1/74 (1.4%)	1	0/78 (0%)	0
Visual acuity reduced	1/74 (1.4%)	1	0/78 (0%)	0
Vitreous floaters	1/74 (1.4%)	1	0/78 (0%)	0
General disorders
Instillation site reaction	0/74 (0%)	0	1/78 (1.3%)	1
Influenza like illness	0/74 (0%)	0	1/78 (1.3%)	1
Immune system disorders
Seasonal allergy	0/74 (0%)	0	1/78 (1.3%)	1
Infections and infestations
Hypopyon, Keratitis bacterial, Keratitis herpetic, Corneal infection, Dacryocanaliculitis, Dacryocys	3/74 (4.1%)	3	9/78 (11.5%)	9
Device related infection, Gastroenteritis, Oral herpes, Urinary tract infection	4/74 (5.4%)	4	0/78 (0%)	0
Injury, poisoning and procedural complications
Femoral neck fracture, Road traffic accident	1/74 (1.4%)	1	1/78 (1.3%)	1
Investigations
Vital dye staining cornea present	0/74 (0%)	0	1/78 (1.3%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	0/74 (0%)	0	1/78 (1.3%)	1
Nervous system disorders
Headache	0/74 (0%)	0	3/78 (3.8%)	3
Reproductive system and breast disorders
Begnin prostatic hyperplasia	1/74 (1.4%)	1	0/78 (0%)	0
Skin and subcutaneous tissue disorders
Nail bed bleeding	1/74 (1.4%)	1	0/78 (0%)	0
Surgical and medical procedures
Tooth extraction	0/74 (0%)	0	1/78 (1.3%)	1
Vascular disorders
Hyperaemia	0/74 (0%)	0	1/78 (1.3%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

All the results of the Trial are the sole and exclusive property of THEA, and cannot be used in whatever form without prior written agreement of THEA.