Retinal Imaging in CNTF -Releasing Encapsulated Cell Implant Treated Patients for Early-stage Retinitis Pigmentosa

• ClinicalTrials.gov Identifier: NCT01530659
• Recruitment Status: Completed
• First Posted: February 10, 2012
• Results First Posted: February 14, 2023
• Last Update Posted: February 14, 2023
• Sponsor: Neurotech Pharmaceuticals
• Collaborator: University of California, San Francisco
• Information provided by (Responsible Party): Neurotech Pharmaceuticals

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Conditions: Retinitis Pigmentosa; Usher Syndrome Type 2; Usher Syndrome Type 3
• Interventions: Drug: NT-501; Procedure: Sham
• Enrollment: 22

Participant Flow

Recruitment Details

Eligible subjects were >18 years old with retinitis pigmentosa or Usher syndrome and adaptive optics scanning laser ophthalmoscopy (AOSLO) images in each eye with at least 7 regions having at least 50 contiguous unambiguous cones in the central 5.7 degrees of the macula at 2 baseline visits. Exclusion criteria included visual acuity worse than 20/40, lens opacity, > -6.00 D myopia, nystagmus, cystoid macular edema, retinal vascular disease, unstable fixation, and severe hearing loss.

Pre-assignment Details

Arm/Group Title	NT-501 Implant		Sham Surgery
Arm/Group Description	A pre-determined randomization scheme will be utilized to designate each of the patient's eyes as the primary eye (to receive the NT-501 implant) or the fellow eye (Control-to receive sham surgery). Primary eye will receive the NT-501 implant		A pre-determined randomization scheme will be utilized to designate each of the patient's eyes as the primary eye (to receive the NT-501 implant) or the fellow eye (Control-to receive sham surgery).
Period Title: Overall Study
	Number of participants	Number of units (Eyes)	Number of participants	Number of units (Eyes)
Started [1]	22	22	22	22
Completed	22	22	22	22
Not Completed	0	0	0	0
[1] 22 total participants and 44 eyes

Baseline Characteristics

Arm/Group Title		NT-501 Implant	Sham Surgery	Total
Arm/Group Description		A pre-determined randomization scheme will be utilized to designate each of the patient's eyes as the primary eye (to receive the NT-501 implant) or the fellow eye (Control-to receive sham surgery). Primary eye will receive the NT-501 implant	A pre-determined randomization scheme will be utilized to designate each of the patient's eyes as the primary eye (to receive the NT-501 implant) or the fellow eye (Control-to receive sham surgery).	Total of all reporting groups
Overall Number of Baseline Participants		22	22	22
Overall Number of Units Analyzed; Type of Units Analyzed: Eyes		22	22	44
Baseline Analysis Population Description		44 eyes of 22 patients were randomized to receive either NT-501 implant or sham surgery.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	22 participants	22 participants	22 participants
		39.8 (11.9)	39.8 (11.9)	39.8 (11.9)
Sex: Female, Male; Count of Units; Unit of measure: Eyes
	Number Analyzed	22 Eyes	22 Eyes	44 Eyes
	Female	9 40.9%	9 40.9%	18 40.9%
	Male	13 59.1%	13 59.1%	26 59.1%
Ethnicity (NIH/OMB); Count of Units; Unit of measure: Eyes
	Number Analyzed	22 Eyes	22 Eyes	44 Eyes
	Hispanic or Latino	2 9.1%	2 9.1%	4 9.1%
	Not Hispanic or Latino	20 90.9%	20 90.9%	40 90.9%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
Race (NIH/OMB); Count of Units; Unit of measure: Eyes
	Number Analyzed	22 Eyes	22 Eyes	44 Eyes
	American Indian or Alaska Native	1 4.5%	1 4.5%	2 4.5%
	Asian	2 9.1%	2 9.1%	4 9.1%
	Native Hawaiian or Other Pacific Islander	1 4.5%	1 4.5%	2 4.5%
	Black or African American	0 0.0%	0 0.0%	0 0.0%
	White	18 81.8%	18 81.8%	36 81.8%
	More than one race	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
Region of Enrollment; Measure Type: Number; Unit of measure: Eyes
United States	Number Analyzed	22 Eyes	22 Eyes	44 Eyes
		22	22	44

Outcome Measures

1. Primary Outcome

Title	Mean Change in Cone Spacing in Arcminutes (Z Score) of 2 Baseline Values Were Compared With Measurements Obtained at Post-op Month 36
Description	Average of cone spacing (nearest neighbor distance) at all regions of interest with at least 50 contiguous unambiguous cones identified over the central 5.7 degrees of the macula using confocal AOSLO at two baseline visits within each eye. Cone spacing measures were converted to Z scores based on normal mean values at similar distances from the fovea from a database of 27 age-similar normal eyes. The mean of 2 baseline cone spacing Z-score values were subtracted from the cone spacing Z score values obtained at post-op month 36 A Z-score of 0 represents the mean cone spacing value at the distance from the fovea measured from 27 healthy subjects. A Z-score greater than +2 represents an abnormally increased cone spacing value at the distance from the fovea where the measurement was performed. This suggests fewer cones are present than normal at that location.
Time Frame	Post-op Month 36

Outcome Measure Data

Analysis Population Description

Measure type: difference from mean baseline to 36 months in change between intervention and control eyes in mean cone spacing Z score averaged over regions of interest in each eye.

Arm/Group Title	NT-501 Implant	Sham Surgery
Arm/Group Description:	A pre-determined randomization scheme will be utilized to designate each of the patient's eyes as the primary eye (to receive the NT-501 implant) or the fellow eye (Control-to receive sham surgery). Primary eye will receive the NT-501 implant	A pre-determined randomization scheme will be utilized to designate each of the patient's eyes as the primary eye (to receive the NT-501 implant) or the fellow eye (Control-to receive sham surgery).
Overall Number of Participants Analyzed	22	22
Overall Number of Units Analyzed; Type of Units Analyzed: Eyes	22	22
Mean (Standard Deviation); Unit of Measure: Difference in change in Z score
	1.13 (1.03)	0.85 (1.78)

2. Secondary Outcome

Title	Difference in logMAR Visual Acuity Change Between CNTF- and Sham Treated Eyes
Description	Difference in change in logMAR visual acuity between NT-501 and contralateral sham-treated eyes. Change in visual acuity was measured based on the number of letters read on a vision chart using a standard protocol. The log of the mean angle of resolution (logMAR) was used to describe the size of the smallest letters that the patient could read. A logMAR value of 0.00 corresponds to visual acuity of 20/20, a logMAR value of 0.3 corresponds to visual acuity of 20/40, a logMAR value of 0.7 corresponds to visual acuity of 20/100, and a logMAR value of 1.00 corresponds to visual acuity of 20/200.
Time Frame	Post-op Month 36

Outcome Measure Data

Analysis Population Description

Difference in change in logMAR visual acuity between NT-501 and contralateral sham-treated eyes.

Arm/Group Title	NT-501 Implant	Sham Surgery
Arm/Group Description:	A pre-determined randomization scheme will be utilized to designate each of the patient's eyes as the primary eye (to receive the NT-501 implant) or the fellow eye (Control-to receive sham surgery). Primary eye will receive the NT-501 implant	A pre-determined randomization scheme will be utilized to designate each of the patient's eyes as the primary eye (to receive the NT-501 implant) or the fellow eye (Control-to receive sham surgery).
Overall Number of Participants Analyzed	22	22
Overall Number of Units Analyzed; Type of Units Analyzed: Eyes	22	22
Mean (Standard Deviation); Unit of Measure: logMAR
	0.004 (0.010)	0.014 (0.082)

Adverse Events

Time Frame	Serious and Other (Not Including Serious) Adverse Events were collected only for randomized participants through study completion, an average of 36 months. However, mortality is noted for one participant who passed away due to unrelated issues before being randomized.
Adverse Event Reporting Description	Non-ocular, Non-serious adverse events were not required to be collected per protocol. All-Cause Mortality and Non-Ocular Serious Adverse Events are reported at the participant level. Ocular Serious and Other (Not Including Serious) Adverse Events are presented with total number of eyes monitored/assessed as the at Risk population.
Arm/Group Title	NT-501 Implant		Sham Surgery		Prior to Randomization
Arm/Group Description	A pre-determined randomization scheme will be utilized to designate each of the patient's eyes as the primary eye (to receive the NT-501 implant) or the fellow eye (Control-to receive sham surgery). Primary eye will receive the NT-501 implant		A pre-determined randomization scheme will be utilized to designate each of the patient's eyes as the primary eye (to receive the NT-501 implant) or the fellow eye (Control-to receive sham surgery).		One participant was consented and enrolled but died before being randomized to receive the study intervention.
All-Cause Mortality
	NT-501 Implant		Sham Surgery		Prior to Randomization
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	0/22 (0.00%)		0/22 (0.00%)		1/1 (100.00%)
Serious Adverse Events
	NT-501 Implant		Sham Surgery		Prior to Randomization
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/22 (18.18%)		4/22 (18.18%)		0/0
Cardiac disorders
Reversible Cardiac Vasospasm *	1/22 (4.55%)		1/22 (4.55%)		0/0	0
Eye disorders
Total Eye Disorders *	4/22 (18.18%)	5	1/22 (4.55%)	1	0/0	0
Clinically Significant Cystoid Macular Edema †	1/22 (4.55%)		0/22 (0.00%)		0/0	0
Secondary Surgical Intervention (excluding Posterior Capsulotomy) † [1]	1/22 (4.55%)		1/22 (4.55%)		0/0	0
Ocular discomfort †	1/22 (4.55%)		0/22 (0.00%)		0/0	0
Reduced peripheral visual field †	1/22 (4.55%)		0/22 (0.00%)		0/0	0
Pregnancy, puerperium and perinatal conditions
Pregnancy *	1/22 (4.55%)		1/22 (4.55%)		0/0	0
* Indicates events were collected by non-systematic assessment; † Indicates events were collected by systematic assessment; [1] Bilateral cataract extraction at 30 months required early NT-501 implant removal.
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	NT-501 Implant		Sham Surgery		Prior to Randomization
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/22 (9.09%)		1/22 (4.55%)		0/0
Eye disorders
Epiretinal membrane †	1/22 (4.55%)		0/22 (0.00%)		/0
Musculoskeletal and connective tissue disorders
Pelvic fracture †	1/22 (4.55%)		1/22 (4.55%)		/0
† Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS 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.

Results Point of Contact

• Name/Title: Neurotech, Sr. Director of Clinical Operations
• Organization: Neurotech USA, Inc.
• Phone: 629-333-5804
• EMail: p.davis@neurotechusa.com

Publications:

Duncan JL, Zhang Y, Gandhi J, Nakanishi C, Othman M, Branham KE, Swaroop A, Roorda A. High-resolution imaging with adaptive optics in patients with inherited retinal degeneration. Invest Ophthalmol Vis Sci. 2007 Jul;48(7):3283-91. doi: 10.1167/iovs.06-1422.

Sieving PA, Caruso RC, Tao W, Coleman HR, Thompson DJ, Fullmer KR, Bush RA. Ciliary neurotrophic factor (CNTF) for human retinal degeneration: phase I trial of CNTF delivered by encapsulated cell intraocular implants. Proc Natl Acad Sci U S A. 2006 Mar 7;103(10):3896-901. doi: 10.1073/pnas.0600236103. Epub 2006 Feb 27.

Talcott KE, Ratnam K, Sundquist SM, Lucero AS, Lujan BJ, Tao W, Porco TC, Roorda A, Duncan JL. Longitudinal study of cone photoreceptors during retinal degeneration and in response to ciliary neurotrophic factor treatment. Invest Ophthalmol Vis Sci. 2011 Apr 6;52(5):2219-26. doi: 10.1167/iovs.10-6479.

• Responsible Party: Neurotech Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01530659
• Other Study ID Numbers: AOSLO-CNTF-FFB-01; FD-R-004100-01A1 ( Other Grant/Funding Number: FDA OOPD )
• First Submitted: January 19, 2012
• First Posted: February 10, 2012
• Results First Submitted: April 22, 2022
• Results First Posted: February 14, 2023
• Last Update Posted: February 14, 2023