Inherited retinal disease (IRD) phenotypically diagnosed as Leber congenital amaurosis (LCA) or retinitis pigmentosa (RP) caused by mutations in the retinal pigment epithelium protein 65 (RPE65) or lecithin:retinol acyltransferase (LRAT) genes MedDRA version: 19.0 Level: PT Classification code 10038914 Term: Retinitis pigmentosa System Organ Class: 10010331 - Congenital, familial and genetic disorders MedDRA version: 19.0 Level: PT Classification code 10070667 Term: Leber's congenital amaurosi
Conditions
Interventions
Product Name: QLT091001
Product Code: QLT091001
Pharmaceutical Form: Oral solution
INN or Proposed INN: Zuretinol Acetate
Other descriptive name: QLT091001
Concentration unit: mg/ml milligram(s)/milli
Sponsors
QLT Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female subjects of any race with IRD (phenotypically diagnosed as LCA or RP by an ocular geneticist or ophthalmologist) caused by pathologic autosomal recessive mutation in RPE65 or LRAT (as determined by a fully accredited certified central genotyping laboratory). 2. Naïve to treatment with QLT091001, gene therapy and surgical implantation of prosthetic retinal chips or sub-retinal injections. 3. 6 to 40 years of age, inclusive. 4. Ability to concentrate and fixate adequately to complete visual field evaluations. 5. In at least one eye and in the same eye: • ETDRS HLHC BCVA of better than 1.5 logMAR (=10 letters at 1 meter); BCVA can be measured a maximum of 3 times between screening (Day -42) and baseline (Day -1) in order to obtain 2 reliable assessments (both assessments must meet the criterion), and • Continuous central visual field solid angle of 0.023-1.130 steradians (corresponding visual field diameter of approximately 10-70 degrees) in each of at least 3 isopters on kinetic perimetry (peripheral islands allowed); perimetry can be assessed a maximum of 6 times between screening (Day -42) and baseline (Day -1) in order to obtain 3 reliable assessments (all 3 assessments must meet the criterion) 6. Pregnancy testing and contraception: • Before study treatment: Females of child-bearing potential must not be pregnant or lactating, must have negative serum pregnancy tests (=25 mIU/mL sensitivity) at screening (i.e., =19 days before Day -1, and on Day -1) and must have been practicing a highly effective method of birth control for at least 1 month. Highly effective methods of birth control include: -Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal) -Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable) -Intrauterine device (IUD) -Intrauterine hormone-releasing system (IUS) -Bilateral tubal occlusion -Vasectomized partner -True abstinence, when this is in line with the preferred and usual lifestyle of the subject (periodic abstinence [e.g., calendar, ovulation, symptothermal post-ovulation methods] and withdrawal are not acceptable methods of contraception) A woman is considered to be of child-bearing potential unless she meets at least one of the following criteria: - Previous bilateral salpingo-oophorectomy or hysterectomy - Premature ovarian failure confirmed by a specialist - XY genotype, Turner syndrome, uterine agenesis - Post-menopausal, defined as 12 consecutive months with no menses without alternative medical cause • During the study: - Females of child-bearing potential must be willing to receive contraceptive counseling before each treatment course. - If the subject is a female under 18 years of age, the legal guardian(s) must agree with the use of contraception. - Females of child-bearing potential must practice a highly effective method of birth control (as described above) during the treatment phase of the study and for 2 months after finishing the last dose of study drug. True abstinence during the trial is defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments (during the treatment phase and for 2 months after finishing the last dose of study drug); periodic abstinence [e.g., calendar ovulation, symptothermal post-ovulation methods], declaration of ab
Exclusion criteria
Exclusion criteria: 1. Presence of any concurrent ocular disease that would affect study outcomes (e.g., severe cataracts; subjects can be enrolled 3 months after successful cataract surgery). 2. Presence of extensive degenerative pigmentary changes throughout the majority of the posterior pole and peripheral retina. This includes both hyper and hypopigmentary (atrophic) changes as determined by the Investigator. 3. Use of any prescription or investigational oral retinoid medication (e.g., isotretinoin or acitretin) within 6 months of screening. 4. Intolerance to previous retinoid medication. 5. Use of any supplements containing =10,000 IU vitamin A within 60 days of screening. 6. Use of any medication that affects bone metabolism within 6 months of screening. 7. Circulating 25-hydroxy vitamin D (25-OHD) 450 milliseconds. 11. History of risk factors for torsade de pointes (e.g., heart failure, hypokalemia, history or family history of Long QT Syndrome), and Wolff-Parkinson-White syndrome. 12. History of diabetes, chronic hyperlipidemia, pancreatitis, hepatitis, cirrhosis, liver failure, or hypervitaminosis A. 13. History of idiopathic elevation of intracranial pressure. 14. Subjects with any of the following findings at screening: • Uncontrolled blood pressure upon repeated measurement (i.e., 2 measurements) taken in a sitting or supine position of the following (by age group): 6-9 years: 120/80 mmHg or higher 10-13 years: 132/83 mmHg or higher 14 years and older: 140/90 mmHg or higher • Resting heart rate upon repeated measurement of the following (unless the subject has a known and documented consistent lower heart rate): 6-9 years: 130 bpm 10-13 years: 105 bpm 14 years and older: 100 bpm • Fasting alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2 times the upper limit of the clinical laboratory value normal range (upon repeated measurement). • Fasting total cholesterol, triglycerides, or LDL >2 times the upper limit of the clinical laboratory value normal range (upon repeated measurement). • Thyroid function tests (upon repeated measurement) indicating uncontrolled thyroid disease in the Investigator’s opinion. • Serum retinol clinical laboratory value above 98 µg/dL or the upper limit of normal, whichever is higher (upon repeated measurement). 15. Known and documented allergy to soy. 16. In the Investigator’s opinion, any severe acute or chronic medical condition, psychiatric condition, physical examination finding or laboratory abnormality that may increase the risk associated with study participation or administration of study treatment, or interfere with the interpretation of study results. 17. Subjects who are actively participating in an experimental therapy study or who have received another experimental therapy within 60 days of screening. 18. Subjects who have lumbar spine bone mineral density worse than -2Z.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: Not applicable;Primary end point(s): Percent change from baseline in visual field volume in the study eye;Timepoint(s) of evaluation of this end point: 12 months, course 12;Main Objective: To evaluate the efficacy, tolerability, pharmacokinetics (PK), and safety of oral QLT091001 in subjects with IRD phenotypically diagnosed as Leber congenital amaurosis (LCA) or retinitis pigmentosa (RP) caused by RPE65 or LRAT gene mutations | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: 12 months, course 12;Secondary end point(s): Secondary Efficacy: • Change from baseline in visual field volume in the study eye • Visual field volume in the study eye • Proportion of subjects with increase in visual field volume in the study eye of at least 10% in Course 12, and proportion of subjects with increase in visual field volume in the study eye of at least 20% in Course 12 • Change from baseline in HLHC BCVA (ETDRS at 4 meters or 1 meter) in the study eye • Change from baseline in LLLC BCVA (ETDRS at 4 meters or 1 meter) in the study eye • Patient reported outcomes | — |
Countries
Brazil, Canada, Denmark, France, Germany, Netherlands, Switzerland, United Kingdom, United States
Contacts
Public ContactMedical Affairs
QLT Inc.
Outcome results
None listed