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Study of Ataluren in Participants With Nonsense Mutation Aniridia (STAR)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02647359
Recruitment Status : Active, not recruiting
First Posted : January 6, 2016
Last Update Posted : June 12, 2019
Sponsor:
Information provided by (Responsible Party):
PTC Therapeutics

Tracking Information
First Submitted Date  ICMJE December 29, 2015
First Posted Date  ICMJE January 6, 2016
Last Update Posted Date June 12, 2019
Actual Study Start Date  ICMJE January 31, 2016
Estimated Primary Completion Date February 21, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 23, 2019)
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: Day 1 to Week 240 ]
Original Primary Outcome Measures  ICMJE
 (submitted: January 4, 2016)
Safety as assessed by systemic and ocular adverse events [ Time Frame: 96 weeks ]
Change History Complete list of historical versions of study NCT02647359 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 23, 2019)
  • Change From Baseline in Visual Acuity at Week 48 [ Time Frame: Baseline, Week 48 ]
  • Change From Baseline in Severity of Corneal Keratopathy at Week 48 [ Time Frame: Baseline, Week 48 ]
  • Change From Baseline in Iris Area at Week 48 [ Time Frame: Baseline, Week 48 ]
  • Change From Baseline in Visual Acuity at Week 240 (Sub-Study End of Treatment Visit) [ Time Frame: Baseline, Week 240 ]
    This endpoint will be assessed only for the cohort of participants who enroll into the sub-study.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 4, 2016)
  • Visual acuity as assessed by the Early Treatment Diabetic Retinopathy Study (ETDRS) chart [ Time Frame: 48 weeks ]
  • Severity of corneal keratopathy as assessed by slit lamp examination and macro photography [ Time Frame: 48 weeks ]
  • Iris area [ Time Frame: 48 weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Ataluren in Participants With Nonsense Mutation Aniridia
Official Title  ICMJE STAR: A Phase 2, Multicenter, Randomized, Double-Masked, Placebo-Controlled Study of the Safety and Efficacy of Ataluren (PTC124) for the Treatment of Nonsense Mutation Aniridia
Brief Summary This study is designed to characterize the systemic and ocular safety profile of ataluren when administered chronically in participants with nonsense mutation aniridia. This study involves a 4-week screening period, a 144-week treatment period (Stage 1: Weeks 1 to 48 [double-masked treatment] and Stage 2: Weeks 49 to 144 [open label treatment]), an optional 96-week open label extension sub-study, and a 4-week post-treatment follow-up period (either study completion or early termination). Participants that choose not to participate in the sub-study will be required to complete the post-treatment follow-up visit at the end of the Stage 2 open-label extension.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Aniridia
Intervention  ICMJE
  • Drug: Ataluren
    Ataluren oral suspension will be administered as per the dose and schedule specified in the respective arms.
    Other Names:
    • PTC124
    • Translarna
  • Drug: Placebo
    Placebo will be administered as per the schedule specified in the respective arm.
Study Arms  ICMJE
  • Experimental: Ataluren
    Participants will receive ataluren orally 3 times a day (TID) at a dose of 10 milligrams per kilogram (mg/kg) in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 48 weeks in Stage 1 (double-masked period) and for additional 96 weeks in Stage 2 (open-label extension period). Participants, who complete Stage 2 and agree to continue in open-label sub-study, will continue to receive ataluren treatment at same dose as mentioned above, for 96 weeks or until commercial availability of ataluren for this indication, whichever is first, or until a positive risk-benefit assessment in this indication is not demonstrated.
    Intervention: Drug: Ataluren
  • Placebo Comparator: Placebo
    Participants will receive placebo matching to ataluren TID orally in the morning, at midday, and in the evening for 48 weeks in Stage 1 (double-masked period) and ataluren orally TID at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for additional 96 weeks in Stage 2 (open-label extension period). Participants, who complete Stage 2 and agree to continue in open-label sub-study, will continue to receive ataluren treatment at same dose as mentioned above, for 96 weeks or until commercial availability of ataluren for this indication, whichever is first, or until a positive risk-benefit assessment in this indication is not demonstrated.
    Interventions:
    • Drug: Ataluren
    • Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: August 2, 2017)
39
Original Estimated Enrollment  ICMJE
 (submitted: January 4, 2016)
36
Estimated Study Completion Date  ICMJE February 21, 2022
Estimated Primary Completion Date February 21, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Evidence of signed and dated informed consent document(s) indicating that the study candidate (and/or a parent/legal guardian) has been informed of all pertinent aspects of the study. Note: If the study candidate is considered a child under local regulation, a parent or legal guardian must provide written consent prior to initiation of study screening procedures and the study candidate may be required to provide written assent. The rules of the responsible institutional review board/independent ethics committee (IRB/IEC) regarding whether one or both parents must provide consent and the appropriate ages for obtaining consent and assent from the participant should be followed.
  • Body weight greater than or equal to (>=) 12 kilograms (kg).
  • Documentation of the presence of a nonsense mutation in 1 allele of the PAX6 gene as determined by genotyping performed at a laboratory certified by the College of American Pathologists (CAP), or under the Clinical Laboratory Improvement Act/Amendment (CLIA), or by an equivalent organization.
  • Clinical diagnosis of aniridia.
  • Willingness and ability to comply with scheduled visits, drug administration plan, study procedures, and study restrictions.
  • Good general health, as determined at Visit 1 (Screening) by medical history and physical examination (including vital sign measurements).
  • No clinically significant abnormality based upon laboratory assessments at Visit 1 (Screening), in the opinion of the investigator.
  • Female participants of childbearing potential are eligible for the study but must be willing to use adequate (at least 1 form of) contraceptive methods as described below during the study treatment period (starting from the day of first dose of study drug and ending 60 days after the last dose of study drug). Childbearing potential is defined as participants who have experienced menarche and who are neither postmenopausal or have been permanently sterilized.

    1. Hormonal methods of contraception (including oral and transdermal contraceptives, injectable progesterone, progestin subdermal implants, progesterone-releasing intrauterine devices [IUDs]) initiated at least 14 days prior to the first dose of study drug
    2. Abstinence
    3. Placement of a copper-containing IUD
    4. Condom with spermicidal foam/gel/film/cream/suppository
    5. Postmenopausal at least 12 months prior to first dose of study drug or permanently sterilized (for example, tubal occlusion, hysterectomy, bilateral salpingectomy)
    6. Male partner who has had a vasectomy for at least 3 months prior to the first dose of study drug
  • Male participants with partners of childbearing potential must agree to use adequate (at least 1 form of) contraception as described below during the study treatment period (starting from the day of first dose of study drug and ending 60 days after the last dose of study drug).

    1. Abstinence
    2. Vasectomy for at least 3 months prior to first dose of study drug or surgically sterile
    3. Without a vasectomy, must use a condom with spermicidal foam/gel/film/cream suppository

Exclusion Criteria:

  • Participants participating in any drug or device clinical investigation within 90 days prior to Visit 1 (Screening) or who anticipate participating in any other drug or device clinical investigation within the duration of this study.
  • Exposure to ataluren within 90 days prior to Visit 1 (Screening).
  • Surgery within 30 days prior to enrollment.
  • Female participants who are pregnant or breastfeeding. Female participants of childbearing potential must have a negative pregnancy test (beta-human chorionic gonadotropin [beta-HCG]) at screening and must use adequate (at least 1 form of) contraceptive methods.
  • Active ocular infection or inflammation.
  • Prior or ongoing medical condition (for example, concomitant illness, alcoholism, drug abuse, psychiatric condition), medical history, physical findings, or laboratory abnormality that, in the investigator's opinion, could adversely affect the safety of the participant, makes it unlikely that the course of study drug administration or follow-up would be completed, or could impair the assessment of study results.
  • Participants with a positive result for hepatitis B, hepatitis C, or human immunodeficiency virus at Visit 1 (Screening).
  • Ongoing warfarin, phenytoin, or tolbutamide therapy.
  • Ongoing intravenous (IV) aminoglycoside or IV vancomycin use.
  • Ongoing systemic cyclosporine therapy. Note: Topical cyclosporine therapy is permitted.
  • Known hypersensitivity to any of the ingredients or excipients of the study drug (polydextrose, polyethylene glycol 3350, poloxamer 407, mannitol 25C, crospovidone XL10, hydroxyethyl cellulose, vanilla, colloidal silica, or magnesium stearate).
  • 20/200 or worse visual acuity in the better eye with best correction.
  • Participants who are monocular.
  • Participants with a history of complications due to ocular surgery that could interfere with the study procedures or assessment of study endpoints.
  • Participants with any other significant ocular or systemic disease that the Investigator determines could interfere with the study.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 2 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02647359
Other Study ID Numbers  ICMJE PTC124-GD-028 ANI
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party PTC Therapeutics
Study Sponsor  ICMJE PTC Therapeutics
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Quintus Ngumah, OD, PhD PTC Therapeutics
PRS Account PTC Therapeutics
Verification Date May 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP