A study in subjects with rare inherited eye conditions caused by gene mutations to see if treatment with QLT091001 is safe and works to improve subjects' vision.

• Register: EUCTR
• Last refreshed on: 28 February 2019
• Main ID: EUCTR2013-005393-22-NL
• Date of registration: 20/09/2016
• Prospective Registration: Yes
• Primary sponsor: QLT Inc.
• Public title: A study in subjects with rare inherited eye conditions caused by gene mutations to see if treatment with QLT091001 is safe and works to improve subjects' vision.
• Scientific title: A Study of the Efficacy and Safety of QLT091001 in Subjects with Inherited Retinal Disease (IRD) Caused by Mutation in Retinal Pigment Epithelium Protein 65 (RPE65) or Lecithin:Retinol Acyltransferase (LRAT)
• Date of first enrolment: 04/01/2019
• Target sample size: 48
• Recruitment status: NA
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-005393-22
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: yes Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Brazil, Canada, Denmark, France, Germany, Netherlands, Switzerland, United Kingdom, United States

Contacts

• Name: Medical Affairs
• Affiliation: QLT Inc.

• Name: Medical Affairs
• Affiliation: QLT Inc.

Key inclusion & exclusion 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 o
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) <20 ng/mL.

8. Use of medications that may interact with alitretinoin, including tetracyclines, ketoconazole, and methotrexate within 60 days of screening.

9. Use of any medication that prolongs the QTc interval within 60 days of screening.

10. Prolongation of QTcB intervals as measured in baseline ECG (repeated demonstration [e.g., 2 of 3 assessments]) with average of >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: <70 bpm or >130 bpm
10-13 years: <45 bpm or >105 bpm
14 years and older: <40 bpm or >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 interpretati

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Eye Diseases [C11]

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 amaurosis System Organ Class: 10010331 - Congenital, familial and genetic disorders

Intervention(s)

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)/millilitre
Concentration type: equal
Concentration number: 20-
Pharmaceutical form of the placebo: Oral solution
Route of administration of the placebo: Oral use

Primary Outcome(s)

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 Objective: Not applicable

Timepoint(s) of evaluation of this end point: 12 months, course 12

Primary end point(s): Percent change from baseline in visual field volume in the study eye

Secondary Outcome(s)

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

Secondary ID(s)

2013-005393-22-DK

RETIRD04

Source(s) of Monetary Support

QLT Inc.