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    The EU Clinical Trials Register currently displays   43881   clinical trials with a EudraCT protocol, of which   7295   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

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    Summary
    EudraCT Number:2021-006456-14
    Sponsor's Protocol Code Number:K321301
    National Competent Authority:Germany - BfArM
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2023-01-25
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedGermany - BfArM
    A.2EudraCT number2021-006456-14
    A.3Full title of the trial
    A Double-Masked, Randomized, Placebo-Controlled, Parallel-Group, 12-Week Administration With Two-Week Gradual Dose Taper Phase and
    38-Week Follow-Up Phase, Phase 3 Study to Investigate the Safety and Efficacy of Ripasudil (K-321) Eye Drops After Descemetorhexis in Subjects with Fuchs Endothelial Corneal Dystrophy
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Study to Investigate the Safety and Effectiveness of Ripasudil (K-321) Eye Drops After Descemetorhexis in Subjects with Fuchs Endothelial Corneal Dystrophy
    A.4.1Sponsor's protocol code numberK321301
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorKowa Research Institute, Inc.
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportKowa Research Institute, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationKowa Research Institute, Inc.
    B.5.2Functional name of contact pointKelsey Behrens
    B.5.3 Address:
    B.5.3.1Street Address430 Davis Drive, Suite 200
    B.5.3.2Town/ cityMorrisville
    B.5.3.3Post codeNC 27560
    B.5.3.4CountryUnited States
    B.5.4Telephone number01770356-8690
    B.5.6E-mailkbehrens@kowaus.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameRipasudil
    D.3.2Product code K-321
    D.3.4Pharmaceutical form Eye drops, solution
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOphthalmic use (Noncurrent)
    Ocular use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNRIPASUDIL
    D.3.9.2Current sponsor codeK-321
    D.3.9.3Other descriptive nameRipasudil
    D.3.9.4EV Substance CodeSUB185276
    D.3.10 Strength
    D.3.10.1Concentration unit % percent
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number0.4
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboEye drops
    D.8.4Route of administration of the placeboOphthalmic use (Noncurrent)
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    In Fuchs endothelial corneal dystrophy (FECD), there is an increased rate of loss of endothelial cells, starting in the centre of Descemet’s membrane and spreading to the periphery, resulting in excrescences known as guttae, which are a marker of the condition. Guttae may coalesce and inhibit the migration of endothelial cells. Eventually the corneal endothelium ceases to function effectively, and the cornea begins to cloud, leading to blindness.
    E.1.1.1Medical condition in easily understood language
    Fuchs endothelial corneal dystrophy (FECD)
    E.1.1.2Therapeutic area Diseases [C] - Eye Diseases [C11]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10011005
    E.1.2Term Corneal dystrophy
    E.1.2System Organ Class 10010331 - Congenital, familial and genetic disorders
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To investigate the effect of K-321 on the time to improvement in best corrected visual acuity (BCVA) by Early Treatment Diabetic Retinopathy Study (ETDRS) letter score of ≥40 letters during the first 12 weeks after descemetorhexis in subjects with FECD.
    E.2.2Secondary objectives of the trial
    The key secondary objective of this study is to investigate the effect of K-321 on:
    • The time to improvement in BCVA by ETDRS letter score of ≥20 letters.
    • The time to achievement of BCVA by ETDRS letter score of ≥70 letters.
    • Central corneal ECD.

    The secondary objectives (efficacy) of this study are to investigate the effect of K-321 on:
    • The time to complete clearance of corneal edema in both areas (epithelial, stromal)
    • The time to return of central corneal thickness to less than or equal to baseline level
    • The time to failure of therapy (defined as events of rescue treatments other than keratoplasty, study drug discontinuation due to lack of efficacy, and withdrawal from the study due to lack of efficacy)
    • On the time to undergo rescue therapy (keratoplasty) or rescue treatment.

    The secondary objective (safety) of this study is as follows:
    • To assess the safety and tolerability of K-321 in subjects with FECD after descemetorhexis.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Pre-DSO Criteria
    Each subject who is planning to undergo DSO must meet all of the following criteria to be enrolled in the study:
    1. Is at least 18 years old at the screening visit (Visit 1)
    2. Has a diagnosis of FECD at Visit 1
    3. Has confluent central guttae in the study eye that can be removed by descemetorhexis of a circular area of 5.5 mm diameter or less (at Visit 1)
    4. Study eye with BCVA of 75 letters or fewer by ETDRS testing (Snellen equivalent of 20/32 or worse) at Visit 1.
    5. Can understand the written informed consent, provides signed and witnessed written informed consent, and agrees to comply with protocol requirements before any study-specific assessments are performed.

    Post-DSO Criteria
    6. The study eye descemetorhexis at Visit 2 is confirmed to have excised a central area with confluent guttae and a diameter of 4.5 to 5.5 mm.
    E.4Principal exclusion criteria
    Subjects meeting any of the following criteria will be excluded from the study:
    1. Is a female subject of childbearing potential and any of the following is true:
    a. is pregnant or lactating/breastfeeding, or
    b. is not surgically sterile, not post-menopausal (no menses for the previous 12 months), or not practicing an effective method of birth control as determined by the Investigator
    [If a subject is female and of childbearing potential, she must have a negative urine pregnancy test result at Visit 2 before the descemetorhexis. Women of childbearing potential must also agree to use effective contraception throughout the study. A female of childbearing potential is defined as a woman who has experienced menarche and has not undergone successful surgical sterilization or is not post-menopausal, and a post-menopausal woman is defined as having had no menses for the previous 12 months (without a known cause)]
    2. Has a study eye with confluent guttae in the periphery or confluent guttae outside the stripped area (individual guttae are allowed) after descemetorhexis
    (Note that subjects may have individual or a small number of guttae remaining outside the stripped area, but there should be no areas with confluent guttae remaining after the descemetorhexis. For example, a subject who has five to ten guttae remaining in a few spots around the circumference of the descemetorhexis would not be excluded by this criterion.)
    3. Has a study eye with baseline (pre-DSO) peripheral ECD ungradable for any area (nasal, temporal, superior, and inferior) due to any reason other than a medical reason
    4. Has a study eye with a history of cataract surgery within 90 days of Visit 1
    5. Has a study eye with a history of any previous intraocular surgery other than for cataract prior to Visit 1
    6. Has a non-study eye with a history of any previous intraocular surgery within 30 days of Visit 1
    7. Plans to receive any surgical treatment on the study eye, other than the study descemetorhexis, during the duration of the study
    8. Plans to receive any surgical treatment for FECD or cataract on the non-study eye during either the screening or treatment period
    9. Has advanced corneal stromal edema, which is defined as the presence of widespread haze or bullae on slit lamp examination at Visits 1 and 2
    10. Has a study eye with central corneal thickness ≥ 670 μm at Visits 1 and 2
    11. Has known severe comorbidities that may interfere with descemetorhexis
    12. Has any clinically significant ocular condition, other than FECD, cataract, primary open-angle glaucoma* or dry eye in the study eye that requires medication or ocular surgery
    (* Only primary open-angle glaucoma is allowed, NOT angle closure or any secondary glaucomas. Use of a single glaucoma medication, except for any carbonic anhydrase inhibitor [CAI] or ROCK inhibitor, is acceptable. Prior YAG-laser surgery is acceptable, but incisional surgery and micro invasive glaucoma surgery are not allowed.)
    13. Has diabetes with poor blood sugar control, defined as hemoglobin A1c (HbA1c) value > 8.5% at Visit 1
    14. Has used either collagen shield or contact lenses in either one eye or both eyes within 7 days of Visit 1
    15. Is unwilling to stop use of either collagen shield or contact lenses for the duration of the study
    16. Has hypersensitivity to any ophthalmic medication used for diagnosis or treatment, including eye drops containing antibiotic(s) or glucocorticoid(s)
    17. Has known hypersensitivity to any component of the study drugs
    18. Has previously used ripasudil
    19. Has used netarsudil or eye drops and ointments containing ≥ 2% sodium chloride within 14 days prior to Visit 1
    20. Has participated in any investigational drug or device clinical studies within 30 days of Visit 1 or is planning to participate in any investigational drug or device clinical studies during the study period.
    21. Has a positive urine test result for drugs of abuse or alcohol at screening; however, drugs prescribed to treat current medical conditions are allowed
    22. Is a member or a family member of the professional or ancillary personnel working at the study site or the Sponsor involved in the study
    23. Has a concomitant medical or psychological condition that could interfere with study participation or is otherwise not suitable for entry into the study in the opinion of the Investigator.
    24. Is using any prohibited prescription or over-the-counter (OTC) medications or devices and is unwilling or unable to discontinue these medications or devices for the required time period before entry into the study
    25. Is committed to an institution by virtue of an order issued either by the judicial or the administrative authorities
    26. Has any ocular disease that may affect visual acuity in the study eye, such as glaucoma that has progressed to the central visual field, age-related macular degeneration, diabetic macular edema, amblyopia, etc
    E.5 End points
    E.5.1Primary end point(s)
    The primary efficacy endpoint is the Time to ≥40 ETDRS letter improvement in BCVA during the first 12 weeks after descemetorhexis.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Week 12
    E.5.2Secondary end point(s)
    The secondary efficacy endpoints are:
    • Time to ≥20 ETDRS letter improvement during the first 12 weeks after descemetorhexis.
    • Time to achievement of ≥70 ETDRS letters during the first 12 weeks after descemetorhexis.
    • Central corneal ECD change from baseline at Week 12.
    • Time to complete clearance of corneal edema in both areas (epithelial, stromal) during the first 12 weeks and during the 52-week period after descemetorhexis.
    • Time to return of central corneal thickness to less than or equal to baseline level during the first 12 weeks and during the 52-week period after descemetorhexis.
    • Time to failure of therapy (defined as events of rescue keratoplasty, rescue treatments other than keratoplasty, study drug discontinuation due to lack of efficacy, and withdrawal from the study due to lack of efficacy) during the 52-week period after descemetorhexis.
    • Time to undergo rescue therapy (keratoplasty) or rescue treatment during the 52-week period after descemetorhexis.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Week 12 and Week 52
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned8
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA20
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Canada
    United Kingdom
    United States
    Denmark
    Germany
    Spain
    E.8.7Trial has a data monitoring committee No
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    The end-of-study (EOS) is defined as a subject considered to have completed the study if he/she has completed the 12-week treatment and the 40-week follow-up period, including the last scheduled procedure shown in the Schedule of Events (Table 1). The common study end date is defined as the date of the last visit of the last subject in the study globally.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years1
    E.8.9.1In the Member State concerned months4
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months4
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 46
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 54
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state30
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 30
    F.4.2.2In the whole clinical trial 100
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    Standard of Care, as deemed appropriate by investigator
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2023-05-10
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2023-03-27
    P. End of Trial
    P.End of Trial StatusOngoing
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