Pharmacodynamic Study of Emixustat Hydrochloride in Subjects With Macular Atrophy Secondary to Stargardt Disease

• Sponsor: Kubota Vision Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03033108
• Collaborator: (none)
• Enrollment: 23
• Location: 1
• Arms: 3
• Actual Duration (Months): 11
• Patients Per Site Per Month: 2.1

Study Details

Study Description

Brief Summary

This is a pharmacodynamics study of emixustat hydrochloride in subjects with macular atrophy secondary to Stargardt disease.

Condition or Disease	Intervention/Treatment	Phase
Stargardt Disease; Macular Atrophy	Drug: Emixustat	Phase 2

Detailed Description

This is a multicenter, randomized, masked study to characterize the pharmacodynamics, safety and tolerability of emixustat in subjects with macular atrophy secondary to Stargardt disease.

Study Design

• Study Type: Interventional
• Actual Enrollment: 23 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 2a Multicenter, Randomized, Masked Study Evaluating the Pharmacodynamics of Emixustat Hydrochloride in Subjects With Macular Atrophy Secondary to Stargardt Disease
• Actual Study Start Date: Jan 1, 2017
• Actual Primary Completion Date: Nov 1, 2017
• Actual Study Completion Date: Dec 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Emixustat Dose 1 lowest dose of once-daily oral emixustat	Drug: Emixustat; Once daily, tablet for oral administration; Other Names: emixustat hydrochloride
Experimental: Emixustat Dose 2 middle dose of once-daily oral emixustat	Drug: Emixustat; Once daily, tablet for oral administration; Other Names: emixustat hydrochloride
Experimental: Emixustat Dose 3 highest dose of once-daily oral emixustat	Drug: Emixustat; Once daily, tablet for oral administration; Other Names: emixustat hydrochloride

Outcome Measures

Primary Outcome Measures

1. Change in Electrical Response of the Retina to a Flash of Light, as Measured by Electroretinogram [Baseline and 1 month]

   Percent suppression compared to baseline of rod b-wave amplitude recovery after a photobleaching light.

Secondary Outcome Measures

1. Percentage of Subjects With Adverse Events, by Severity and Seriousness [1 month]

   Assessment of safety profile

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria, including, but not limited to:

• Clinical diagnosis of macular atrophy (MA) secondary to Stargardt disease (STGD) in one or both eyes

• At least 2 pathogenic mutations of the ABCA4 gene

• Early Treatment Diabetic Retinopathy Study BCVA of ≥ 20 letters (approximately ≥ 20/400 Snellen) in the study eye

• Adequate clarity of ocular media and adequate pupillary dilation to permit good quality imaging of MA in the study eye

• Able and willing to provide written informed consent before undergoing any study-related procedures

• Able to reliably administer oral medication by self or with available assistance

Exclusion Criteria, including, but not limited to:

• Macular atrophy associated with a condition other than STGD in either eye.

• Presence in either eye of an active ocular disease that in the opinion of the Investigator compromises or confounds visual function.

• History of any intraocular or ocular surface surgery in either eye within 3 months of screening.

• Current or previous participation in an interventional study to treat STGD using gene therapy or stem cell therapy at any time, or participation in an interventional study of a vitamin A derivative ≤3 months prior to screening.

• Pre-specified laboratory abnormalities at screening

• Presence of other medical or ophthalmic disease, physical examination finding, or clinical laboratory finding that in the opinion of the Investigator may contraindicate the use of an investigational drug and place the subject at risk

• Current or history of cancer (except for adequately treated basal cell or squamous cell carcinoma of the skin) within 1 year of screening

• History of myocardial infarction, stroke, unstable ischemic heart disease, uncontrolled cardiac arrhythmia, or hospitalization for congestive heart failure within 6 months of screening.

• Anticipated hospitalization for a medical/surgical procedure(s) that could result in interruption/premature cessation of study treatment or participation.

• Electrocardiogram with a clinically significant abnormal finding

• Female subjects who are pregnant or lactating

• Female subjects of childbearing potential or male subjects who are not surgically sterile who are not willing to practice a medically accepted method of birth control with their sexual partner from screening through 30 days after the final dose of study drug

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Dallas	Texas	United States	75231

Sponsors and Collaborators

• Kubota Vision Inc.

Investigators

• Study Director: Acucela Medical Director, MD, Kubota Vision Inc.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jul 13, 2017

More Information

Publications

None provided.

• Responsible Party: Kubota Vision Inc.
• ClinicalTrials.gov Identifier: NCT03033108
• Other Study ID Numbers: 4429-204
• First Posted: Jan 26, 2017
• Last Update Posted: May 19, 2021
• Last Verified: Apr 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Stargardt Disease; Macular Degeneration; Anetoderma; Atrophy

Study Results

Participant Flow

Recruitment Details	Subjects were recruited at 6 sites in the United States from January to September 2017

Arm/Group Title	Emixustat Dose 1	Emixustat Dose 2	Emixustat Dose 3
Arm/Group Description	lowest dose of once-daily oral emixustat Emixustat: Once daily, tablet for oral administration	middle dose of once-daily oral emixustat Emixustat: Once daily, tablet for oral administration	highest dose of once-daily oral emixustat Emixustat: Once daily, tablet for oral administration
Period Title: Overall Study
STARTED	7	9	7
COMPLETED	7	8	7
NOT COMPLETED	0	1	0

Baseline Characteristics

Arm/Group Title	Emixustat Dose 1	Emixustat Dose 2	Emixustat Dose 3	Total
Arm/Group Description	lowest dose of once-daily oral emixustat Emixustat: Once daily, tablet for oral administration	middle dose of once-daily oral emixustat Emixustat: Once daily, tablet for oral administration	highest dose of once-daily oral emixustat Emixustat: Once daily, tablet for oral administration	Total of all reporting groups
Overall Participants	7	9	7	23
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	53.6	54.3	46.3	51.6
Sex: Female, Male (Count of Participants)
Female	4 57.1%	1 11.1%	3 42.9%	8 34.8%
Male	3 42.9%	8 88.9%	4 57.1%	15 65.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 14.3%	0 0%	0 0%	1 4.3%
Not Hispanic or Latino	6 85.7%	9 100%	7 100%	22 95.7%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	1 11.1%	0 0%	1 4.3%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	2 28.6%	1 11.1%	1 14.3%	4 17.4%
White	5 71.4%	7 77.8%	6 85.7%	18 78.3%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	7 100%	9 100%	7 100%	23 100%
Number of ABCA4 gene mutations (Count of Participants)
One mutation	1 14.3%	2 22.2%	2 28.6%	5 21.7%
Two mutations	6 85.7%	7 77.8%	5 71.4%	18 78.3%

Outcome Measures

1. Primary Outcome

Title	Change in Electrical Response of the Retina to a Flash of Light, as Measured by Electroretinogram
Description	Percent suppression compared to baseline of rod b-wave amplitude recovery after a photobleaching light.
Time Frame	Baseline and 1 month

Outcome Measure Data

Analysis Population Description

Subjects with evaluable ERGs at both Baseline and Month 1

Arm/Group Title	Emixustat Dose 1	Emixustat Dose 2	Emixustat Dose 3
Arm/Group Description	lowest dose of once-daily oral emixustat Emixustat: Once daily, tablet for oral administration	middle dose of once-daily oral emixustat Emixustat: Once daily, tablet for oral administration	highest dose of once-daily oral emixustat Emixustat: Once daily, tablet for oral administration
Measure Participants	6	7	6
Median (Full Range) [percent suppression]	-12.23	68.00	96.69

2. Secondary Outcome

Title	Percentage of Subjects With Adverse Events, by Severity and Seriousness
Description	Assessment of safety profile
Time Frame	1 month

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Emixustat Dose 1	Emixustat Dose 2	Emixustat Dose 3
Arm/Group Description	lowest dose of once-daily oral emixustat Emixustat: Once daily, tablet for oral administration	middle dose of once-daily oral emixustat Emixustat: Once daily, tablet for oral administration	highest dose of once-daily oral emixustat Emixustat: Once daily, tablet for oral administration
Measure Participants	7	9	7
Subjects with 1 or more adverse events	6 85.7%	8 88.9%	6 85.7%
Subjects with 1 or more mild adverse events	5 71.4%	5 55.6%	4 57.1%
Subjects with 1 or more moderate adverse events	1 14.3%	2 22.2%	2 28.6%
Subjects with 1 or more severe adverse events	0 0%	1 11.1%	1 14.3%
Subjects with 1 or more serious adverse events	0 0%	0 0%	0 0%

Adverse Events

Time Frame	1 month
Arm/Group Title	Emixustat Dose 1		Emixustat Dose 2		Emixustat Dose 3
Arm/Group Description	lowest dose of once-daily oral emixustat Emixustat: Once daily, tablet for oral administration		middle dose of once-daily oral emixustat Emixustat: Once daily, tablet for oral administration		highest dose of once-daily oral emixustat Emixustat: Once daily, tablet for oral administration
All Cause Mortality
	Emixustat Dose 1		Emixustat Dose 2		Emixustat Dose 3
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/7 (0%)		0/9 (0%)		0/7 (0%)
Serious Adverse Events
	Emixustat Dose 1		Emixustat Dose 2		Emixustat Dose 3
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/7 (0%)		0/9 (0%)		0/7 (0%)
Other (Not Including Serious) Adverse Events
	Emixustat Dose 1		Emixustat Dose 2		Emixustat Dose 3
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/7 (85.7%)		8/9 (88.9%)		7/7 (100%)
Eye disorders
Delayed Dark Adaptation	1/7 (14.3%)		6/9 (66.7%)		4/7 (57.1%)
Erythropsia	1/7 (14.3%)		3/9 (33.3%)		1/7 (14.3%)
Vision blurred	2/7 (28.6%)		1/9 (11.1%)		1/7 (14.3%)
Photophobia	1/7 (14.3%)		2/9 (22.2%)		0/7 (0%)
Visual impairment	1/7 (14.3%)		1/9 (11.1%)		1/7 (14.3%)
Blindness day	0/7 (0%)		1/9 (11.1%)		1/7 (14.3%)
Chromatopsia	0/7 (0%)		0/9 (0%)		2/7 (28.6%)
Night blindness	0/7 (0%)		1/9 (11.1%)		1/7 (14.3%)
Xanthopsia	0/7 (0%)		1/9 (11.1%)		1/7 (14.3%)
Asthenopia	1/7 (14.3%)		0/9 (0%)		0/7 (0%)
Eye Pain	1/7 (14.3%)		0/9 (0%)		0/7 (0%)
Eye Pruritis	1/7 (14.3%)		0/9 (0%)		0/7 (0%)
Lenticular opacities	0/7 (0%)		0/9 (0%)		1/7 (14.3%)
Visual acuity reduced	0/7 (0%)		0/9 (0%)		1/7 (14.3%)
Infections and infestations
Upper respiratory tract infections	0/7 (0%)		1/9 (11.1%)		0/7 (0%)
Investigations
Blood bilirubin increased	0/7 (0%)		1/9 (11.1%)		1/7 (14.3%)
Blood creatine phosphokinase increased	0/7 (0%)		1/9 (11.1%)		1/7 (14.3%)
Nervous system disorders
Headache	0/7 (0%)		2/9 (22.2%)		2/7 (28.6%)
Visual field defect	1/7 (14.3%)		0/9 (0%)		0/7 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	1/7 (14.3%)		0/9 (0%)		0/7 (0%)
Rhinorrheoea	1/7 (14.3%)		0/9 (0%)		0/7 (0%)
Skin and subcutaneous tissue disorders
Dermatitis allergic	0/7 (0%)		1/9 (11.1%)		0/7 (0%)
Rash	0/7 (0%)		1/9 (11.1%)		0/7 (0%)

Limitations/Caveats

Small sample size and inherent, significant intersubject and intrasubject variability observed in electroretinography.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.