Study of Ataluren in Participants With Nonsense Mutation Aniridia
Condition: Aniridia
MeSH terms: Aniridia
Intervention: Ataluren; Placebo
Intervention description: Ataluren oral suspension will be administered as per the dose and schedule specified in the respective arms.; Placebo will be administered as per the schedule specified in the respective arm.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 39.0
Sex: All
Minimum age: 2 Years
Healthy volunteers: No

Summary:

      This study is designed to evaluate the effect of ataluren on Maximum Reading Speed as
      measured using the Minnesota Low Vision Reading Test (MNREAD) Acuity Charts 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.
    

Eligibility criteria:

        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 1 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 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 Screening by medical history and physical
             examination (including vital sign measurements).

          -  No clinically significant abnormality based upon laboratory assessments at 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 nor 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 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 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.