Clinical Trial Results:
Efficacy and Safety Assessment of T4030 Eye Drops versus Ganfort® UD
in Ocular Hypertensive or Glaucomatous Patients.
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Summary
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EudraCT number |
2020-003979-18 |
Trial protocol |
FR PL HU BG BE ES IT |
Global end of trial date |
13 Apr 2023
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Results information
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Results version number |
v1(current) |
This version publication date |
10 Nov 2023
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First version publication date |
10 Nov 2023
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
LT4030-301
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04898387 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Laboratoires Thea
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Sponsor organisation address |
12 rue Louis Blériot, Clermont-Ferrand, France, 63017
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Public contact |
Research and Development Department, Laboratoires THEA, Sandrine.Guyon@theapharma.com
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Scientific contact |
Research and Development Department, Laboratoires THEA, Sandrine.Guyon@theapharma.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
11 Jul 2023
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
13 Apr 2023
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Global end of trial reached? |
Yes
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Global end of trial date |
13 Apr 2023
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To demonstrate the non-inferiority of T4030 (unpreserved fixed combination of bimatoprost 0.01% and timolol 0.1%) with Ganfort UD (unpreserved fixed combination of bimatoprost 0.03% and timolol 0.5% eye drops) in terms of efficacy.
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Protection of trial subjects |
Protection of trial subjects:
Different assessments were done during subject visits in order to ensure subject safety:
• Assessment of the conjunctival hyperaemia on McMonnies photographic scale in each eye.
• Corneal fluorescein staining according to Oxford grading scheme in each eye.
• Far Best Corrected Visual Acuity in each eye.
• Ocular tolerance assessed by the investigator and by the patient.
• Ocular and systemic AE reporting.
All AEs experienced by a patient, irrespective of the suspected causality, was monitored until the event has resolved or stabilised at a level acceptable to the investigator and Medical expert, until there is a satisfactory explanation for the changes observed.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
26 Mar 2021
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Poland: 86
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Country: Number of subjects enrolled |
Spain: 18
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Country: Number of subjects enrolled |
United Kingdom: 11
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Country: Number of subjects enrolled |
Belgium: 6
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Country: Number of subjects enrolled |
Bulgaria: 149
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Country: Number of subjects enrolled |
Czechia: 7
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Country: Number of subjects enrolled |
France: 1
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Country: Number of subjects enrolled |
Hungary: 9
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Country: Number of subjects enrolled |
Italy: 51
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Country: Number of subjects enrolled |
India: 85
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Country: Number of subjects enrolled |
Ukraine: 15
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Country: Number of subjects enrolled |
Russian Federation: 58
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Country: Number of subjects enrolled |
Tunisia: 58
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Worldwide total number of subjects |
554
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EEA total number of subjects |
327
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
282
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From 65 to 84 years |
264
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85 years and over |
8
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Recruitment
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Recruitment details |
554 patients (from 645 screened patients) were randomised in the study: 554 patients in the intent-to-treat (ITT) set, 553 in the Safety set, 550 in the modified-ITT (mITT) set and 508 in the per-protocol (PP) set. The recuitment started on 26-MAR-2021 and was completed on 9-Nov -2022 and the last pateint completed tcompleted on 13-Apr-2023 | |||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
Patient with both eyes with diagnosed OHT or open-angle glaucoma currently treated with a first-line monotherapy and insufficiently controlled in the opinion of the investigator, and requiring a dual therapy (bitherapy). Incl/Excl criteria checked at screening visit, then patients discontinued their current treatment to start wash-out period. | |||||||||||||||||||||||||||
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Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Single blind | |||||||||||||||||||||||||||
Roles blinded |
Investigator [1] | |||||||||||||||||||||||||||
Blinding implementation details |
The 2 different treatment kits (T4030 and Ganfort) were identical in external packaging. The identity of the IMP given to each patient was not known by the masked investigator or masked authorised collaborator in charge of the ophthalmic examination and questionnaires, or individuals from the Sponsor in charge of medical evaluation of the data. The masked investigator delegated the recording of used and unused IMPs, to the hospital pharmacy or to a trained collaborator
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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T4030 | |||||||||||||||||||||||||||
Arm description |
T4030 : PF fixed combination bimatoprost 0.01% and timolol 0.1% eye drops presented in UD The patient administered the assigned treatment T4030 once daily at 20:00 (±1 h) in the conjunctival cul-de-sac of each eye for the 3-month treatment period from the randomisation visit (Day 1; Visit #2) to the final visit (Week 12; Day 85±7 days; Visit #4). | |||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||
Investigational medicinal product name |
T4030
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Eye gel in single-dose container
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Routes of administration |
Ocular use
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Dosage and administration details |
The patient administered the assigned treatment (T4030) once daily at 20:00 (±1 h) in the conjunctival cul-de-sac of each eye for 12 weeks.
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Arm title
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Ganfort | |||||||||||||||||||||||||||
Arm description |
Ganfort : PF fixed combination bimatoprost 0.03% and timolol 0.5% eye drops presented in UD The patient administered the assigned treatment Ganfort once daily at 20:00 (±1 h) in the conjunctival cul-de-sac of each eye for the 3-month treatment period from the randomisation visit (Day 1; Visit #2) to the final visit (Week 12; Day 85±7 days; Visit #4). | |||||||||||||||||||||||||||
Arm type |
Active comparator | |||||||||||||||||||||||||||
Investigational medicinal product name |
Ganfort
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Eye gel in single-dose container
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Routes of administration |
Ocular use
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Dosage and administration details |
The patient administered the assigned treatment (Ganfort) once daily at 20:00 (±1 h) in the conjunctival cul-de-sac of each eye for 12 weeks.
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| Notes [1] - The roles blinded appear inconsistent with a simple blinded trial. Justification: The identity of the IMP given to each patient was not known by the masked investigator or masked authorised collaborator in charge of the ophthalmic examination and questionnaires, or individuals from the Sponsor in charge of medical evaluation of the data. The masked investigator delegated the recording of used and unused IMPs, to the hospital pharmacy or to a trained collaborator |
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Baseline characteristics reporting groups
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Reporting group title |
T4030
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Reporting group description |
T4030 : PF fixed combination bimatoprost 0.01% and timolol 0.1% eye drops presented in UD The patient administered the assigned treatment T4030 once daily at 20:00 (±1 h) in the conjunctival cul-de-sac of each eye for the 3-month treatment period from the randomisation visit (Day 1; Visit #2) to the final visit (Week 12; Day 85±7 days; Visit #4). | ||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Ganfort
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Reporting group description |
Ganfort : PF fixed combination bimatoprost 0.03% and timolol 0.5% eye drops presented in UD The patient administered the assigned treatment Ganfort once daily at 20:00 (±1 h) in the conjunctival cul-de-sac of each eye for the 3-month treatment period from the randomisation visit (Day 1; Visit #2) to the final visit (Week 12; Day 85±7 days; Visit #4). | ||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
mITT T4030
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Subject analysis set type |
Modified intention-to-treat | ||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
T4030 arm : All randomised patients having received at least one dose of IMP T4030 with at least one baseline and one post-randomisation efficacy assessment on treatment and considered as-randomised.
m-ITT set will be the primary population for efficacy analysis
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Subject analysis set title |
mITT Ganfort
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Subject analysis set type |
Modified intention-to-treat | ||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Ganfort arm : All randomised patients having received at least one dose of IMP Ganfort with at least one baseline and one post-randomisation efficacy assessment on treatment and considered as-randomised.
m-ITT set will be the primary population for efficacy analysis
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End points reporting groups
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Reporting group title |
T4030
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Reporting group description |
T4030 : PF fixed combination bimatoprost 0.01% and timolol 0.1% eye drops presented in UD The patient administered the assigned treatment T4030 once daily at 20:00 (±1 h) in the conjunctival cul-de-sac of each eye for the 3-month treatment period from the randomisation visit (Day 1; Visit #2) to the final visit (Week 12; Day 85±7 days; Visit #4). | ||
Reporting group title |
Ganfort
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Reporting group description |
Ganfort : PF fixed combination bimatoprost 0.03% and timolol 0.5% eye drops presented in UD The patient administered the assigned treatment Ganfort once daily at 20:00 (±1 h) in the conjunctival cul-de-sac of each eye for the 3-month treatment period from the randomisation visit (Day 1; Visit #2) to the final visit (Week 12; Day 85±7 days; Visit #4). | ||
Subject analysis set title |
mITT T4030
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Subject analysis set type |
Modified intention-to-treat | ||
Subject analysis set description |
T4030 arm : All randomised patients having received at least one dose of IMP T4030 with at least one baseline and one post-randomisation efficacy assessment on treatment and considered as-randomised.
m-ITT set will be the primary population for efficacy analysis
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Subject analysis set title |
mITT Ganfort
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Subject analysis set type |
Modified intention-to-treat | ||
Subject analysis set description |
Ganfort arm : All randomised patients having received at least one dose of IMP Ganfort with at least one baseline and one post-randomisation efficacy assessment on treatment and considered as-randomised.
m-ITT set will be the primary population for efficacy analysis
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End point title |
Change from baseline in IOP | ||||||||||||
End point description |
The primary efficacy endpoint is the change from Baseline (Day 1) to Week 12 in IOP at 08:00 in the study eye.
The study eye is defined as the eligible eye with the highest IOP at baseline at 08:00. In case of no IOP difference between both eyes, the right eye will be considered as the study eye.
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End point type |
Primary
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End point timeframe |
The primary efficacy endpoint is the change from Baseline (Day 1) to Week 12 in IOP at 08:00 in the study eye.
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Statistical analysis title |
Change from Baseline in IOP at 08:00 at week 12 | ||||||||||||
Statistical analysis description |
To assess the efficacy of T4030, on the change from Baseline in IOP at 08:00, a Mixed Model for Repeated Measures (MMRM) approach was used.
The model will include as fixed factors, treatment, scheduled visit time point (Week 6 and Week 12), baseline IOP as covariates, treatment by visit interaction, baseline IOP by visit interaction, and patient as random factor. The Restricted Maximum Likelihood (REML) estimation approach will be used, and the default covariance structure will be unstructured.
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Comparison groups |
mITT T4030 v mITT Ganfort
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Number of subjects included in analysis |
550
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority [1] | ||||||||||||
Method |
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Parameter type |
Adjusted Mean Difference | ||||||||||||
Point estimate |
-0.04
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Confidence interval |
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95% | ||||||||||||
sides |
2-sided
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lower limit |
-0.51 | ||||||||||||
upper limit |
0.43 | ||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
0.24
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| Notes [1] - The non-inferiority testing will be performed based on a two-sided 95% CI on the mean difference in change from baseline in IOP after 12 weeks of treatment. |
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Adverse events information
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Timeframe for reporting adverse events |
Adverse event reporting from start of the treatement (Day 1) until follow-up Phone call (4 weeks±7 days after the last Investigational Medicinal Product (IMP) instillation)
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
24.0
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Reporting groups
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Reporting group title |
Safety Set T4030
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Reporting group description |
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Reporting group title |
Safety Set Ganfort
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
