Study of Ataluren in Participants With Nonsense Mutation Aniridia

• Register: ClinicalTrials.gov
• Last refreshed on: 22 November 2021
• Main ID: NCT02647359
• Date of registration: 29/12/2015
• Prospective Registration: Yes
• Primary sponsor: PTC Therapeutics
• Public title: Study of Ataluren in Participants With Nonsense Mutation Aniridia STAR
• Scientific title: 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
• Date of first enrolment: January 31, 2016
• Target sample size: 39
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02647359
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 2

Countries of recruitment

Canada, United States

Contacts

• Name: Quintus Ngumah, OD, PhD
• Affiliation: PTC Therapeutics

Key inclusion & exclusion 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 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 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 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.



Age minimum: 2 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Aniridia

Intervention(s)

Drug: Placebo

Drug: Ataluren

Primary Outcome(s)

Change From Baseline in Maximum Reading Speed of Oculus Unitas (OU) (Both Eyes) at Week 48, as Measured Using the MNREAD Acuity Charts [Time Frame: Baseline, Week 48]

Secondary Outcome(s)

Change From Baseline in Reading Accessibility Index of OU at Week 48 [Time Frame: Baseline, Week 48]

Change From Baseline in Severity of Corneal Keratopathy at Week 48 as Graded by Duke Reading Center [Time Frame: Baseline, Week 48]

Change From Baseline in Maximum Reading Speed of Oculus Dexter (OD) (Right Eye) and Oculus Sinister (OS) (Left Eye) at Week 48 [Time Frame: Baseline, Week 48]

Change From Baseline in Iris Area at Week 48 [Time Frame: Baseline, Week 48]

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [Time Frame: Day 1 to Week 240]

Change From Baseline in Critical Print Size of OU, OD and OS at Week 48 [Time Frame: Baseline, Week 48]

Change From Baseline in BCVA at Week 240 (Sub-Study End of Study Visit) [Time Frame: Baseline, Week 240]

Change From Baseline in Best Corrected Visual Acuity (BCVA) at Week 48 [Time Frame: Baseline, Week 48]

Change From Baseline in Reading Accessibility Index of OD and OS at Week 48 [Time Frame: Baseline, Week 48]

Change From Baseline in Reading Acuity of OU, OD and OS at Week 48 [Time Frame: Baseline, Week 48]

Secondary ID(s)

PTC124-GD-028 ANI

Source(s) of Monetary Support

Please refer to primary and secondary sponsors