A Study to Assess the Safety, Tolerability and Effectiveness of MT-0814 for the Treatment of Age-related Macular Degeneration

• Sponsor: Senju Pharmaceutical Co., Ltd. (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT03869684
• Collaborator: PPD (Industry)
• Enrollment: 13
• Locations: 13
• Arms: 3
• Actual Duration (Months): 13.9
• Patient Per Site: 1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Age-related macular degeneration (AMD) is the leading cause of blindness among adults in North America. The current standard of care for patients with exudative ("wet") AMD is anti-vascular endothelial growth factor (anti-VEGF) therapy which must be administered by an injection into the eye every 4-8 weeks. MT-0814 is being developed for the treatment of patients with exudative AMD, and could offer an alternative, safer and less burdensome therapy.

Condition or Disease	Intervention/Treatment	Phase
Age-related Macular Degeneration	Drug: MT-0814; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 13 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Double-Masked, Randomized, Multicenter, Placebo-Controlled, Parallel-Group Study to Assess the Safety, Tolerability, and Efficacy of MT-0814 for the Treatment of Patients With Age-Related Macular Degeneration
• Actual Study Start Date: Feb 25, 2019
• Actual Primary Completion Date: Mar 25, 2020
• Actual Study Completion Date: Apr 24, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: MT-0814 High dose	Drug: MT-0814; Randomly assigned dose
Experimental: MT-0814 Low dose MT-0814 plus placebo	Drug: MT-0814; Randomly assigned dose; Drug: Placebo; Placebo manufactured to mimic MT-0814
Placebo Comparator: Placebo	Drug: Placebo; Placebo manufactured to mimic MT-0814

Outcome Measures

Primary Outcome Measures

1. Change in Best-corrected Visual Acuity (BCVA) : Study Eye [Baseline and Week 12]

   Change from Baseline in BCVA. BCVA was measured using an eye chart and is reported as number of letters read correctly using Early Treatment of Diabetic Retinopathy Study (ETDRS) Scale (0 to 100 letters) in study eye. Lower number of letters read correctly, worse the vision. Study eye: eye that meets inclusion criteria. If both eyes meet all inclusion and exclusion criteria, the eye with the lower BCVA at Screening will be selected as the study eye. If both eyes meet all inclusion criteria and have identical BCVA at Screening, selection of the study eye will be at the investigator's discretion.

Secondary Outcome Measures

1. Change in Central Subfield Thickness (CSFT) : Study Eye [Baseline and Week 12]

   Change from Baseline in CSFT, measured by Optical Coherence Tomography (OCT). Study eye: eye that meets inclusion criteria. If both eyes meet all inclusion and exclusion criteria, the eye with the lower BCVA at Screening will be selected as the study eye. If both eyes meet all inclusion criteria and have identical BCVA at Screening, selection of the study eye will be at the investigator's discretion.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Must agree to sign informed consent form, and to comply with protocol requirements, including study visits.

• Must have clear optic media in the study eye that is capable of producing high-quality fundus images.

Exclusion Criteria:

• Has active CNV due to causes other than AMD in the study eye.

• Has retinal vascular disease or retinal degeneration other than AMD in the study eye.

• Has had intraocular surgery, cataract surgery or LASIK surgery on the study eye within 90 days prior to the study.

• Has had yttrium aluminum garnet (YAG) laser capsulotomy on the study eye within 30 days prior to the study.

• Has active inflammation, infection, or other severe ocular disease in either eye.

• Has aphakia in the study eye.

• Has uncontrolled glaucoma or a history of previous glaucoma filter surgery in either eye.

• Is a contact lens wearer and is unable to discontinue their use in both eyes for the duration of the study.

• Has a serious allergy to, or experienced a prior significant adverse reaction to fluorescein angiography (FA) or indocyanine green angiography (ICGA).

• Has participated in any other clinical trial and/or has taken any investigational drug or product within 90 days prior to the study.

Other protocol-defined inclusion/exclusion criteria could apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Senju Investigational Site	Peoria	Arizona	United States	85381
2	Senju Investigational Site	Phoenix	Arizona	United States	85053
3	Senju Investigational Site	Pasadena	California	United States	91107
4	Senju Investigational Site	Redlands	California	United States	92374
5	Senju Investigational Site	Altamonte Springs	Florida	United States	32701
6	Senju Investigational Site	Clearwater	Florida	United States	33761
7	Senju Investigational Site	Melbourne	Florida	United States	32901
8	Senju Investigational Site	Tallahassee	Florida	United States	32308
9	Senju Investigational Site	Arlington	Texas	United States	76012
10	Senju Investigational Site	Houston	Texas	United States	77030
11	Senju Investigational Site	San Antonio	Texas	United States	78240
12	Senju Investigational Site	The Woodlands	Texas	United States	77384
13	Senju Investigational Site	Murray	Utah	United States	84107

Sponsors and Collaborators

• Senju Pharmaceutical Co., Ltd.
• PPD

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Nov 29, 2019

More Information

Additional Information:

• FDA Safety Alerts and Recalls

Publications

None provided.

• Responsible Party: Senju Pharmaceutical Co., Ltd.
• ClinicalTrials.gov Identifier: NCT03869684
• Other Study ID Numbers: MT-0814/2-01
• First Posted: Mar 11, 2019
• Last Update Posted: Apr 20, 2021
• Last Verified: Mar 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Senju Pharmaceutical Co., Ltd.: Exudative; Wet; AMD; Age-related macular degeneration; Age related macular degeneration
• Additional relevant MeSH terms: Macular Degeneration

Study Results

Participant Flow

Arm/Group Title	Placebo	MT-0814 Low Dose	MT-0814 High Dose
Arm/Group Description	Placebo: Placebo manufactured to mimic MT-0814	MT-0814 plus placebo MT-0814: Randomly assigned dose Placebo: Placebo manufactured to mimic MT-0814	MT-0814: Randomly assigned dose
Period Title: Overall Study
STARTED	3	5	5
COMPLETED	1	2	2
NOT COMPLETED	2	3	3

Baseline Characteristics

Arm/Group Title	Placebo	MT-0814 Low Dose	MT-0814 High Dose	Total
Arm/Group Description	Placebo: Placebo manufactured to mimic MT-0814	MT-0814 plus placebo MT-0814: Randomly assigned dose Placebo: Placebo manufactured to mimic MT-0814	MT-0814: Randomly assigned dose	Total of all reporting groups
Overall Participants	3	5	5	13
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	2 66.7%	1 20%	0 0%	3 23.1%
>=65 years	1 33.3%	4 80%	5 100%	10 76.9%
Sex: Female, Male (Count of Participants)
Female	2 66.7%	4 80%	2 40%	8 61.5%
Male	1 33.3%	1 20%	3 60%	5 38.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%	0 0%
Not Hispanic or Latino	3 100%	5 100%	5 100%	13 100%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Whte	3 100%	5 100%	5 100%	13 100%
Other	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	3 100%	5 100%	5 100%	13 100%
Best-corrected Visual Acuity (BCVA) : Study eye (Letters) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Letters]	62.0 (10.82)	66.8 (7.98)	71.2 (4.15)	67.4 (7.74)
Central Subfield Thickness (CSFT) : Study eye (mm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mm]	0.2990 (0.04015)	0.3748 (0.05981)	0.3954 (0.08581)	0.3652 (0.07369)

Outcome Measures

1. Primary Outcome

Title	Change in Best-corrected Visual Acuity (BCVA) : Study Eye
Description	Change from Baseline in BCVA. BCVA was measured using an eye chart and is reported as number of letters read correctly using Early Treatment of Diabetic Retinopathy Study (ETDRS) Scale (0 to 100 letters) in study eye. Lower number of letters read correctly, worse the vision. Study eye: eye that meets inclusion criteria. If both eyes meet all inclusion and exclusion criteria, the eye with the lower BCVA at Screening will be selected as the study eye. If both eyes meet all inclusion criteria and have identical BCVA at Screening, selection of the study eye will be at the investigator's discretion.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

Full-analysis set (FAS): The FAS consisted of all participants who were randomly assigned to receive double-masked study drug and who have received at least 1 dose of study drug. All analyses using the FAS grouped participants according to randomly assigned treatment.

Arm/Group Title	Placebo	MT-0814 Low Dose	MT-0814 High Dose
Arm/Group Description	Placebo: Placebo manufactured to mimic MT-0814	MT-0814 plus placebo MT-0814: Randomly assigned dose Placebo: Placebo manufactured to mimic MT-0814	MT-0814: Randomly assigned dose
Measure Participants	3	5	5
Least Squares Mean (95% Confidence Interval) [letters]	0.4	0.3	0.1

2. Secondary Outcome

Title	Change in Central Subfield Thickness (CSFT) : Study Eye
Description	Change from Baseline in CSFT, measured by Optical Coherence Tomography (OCT). Study eye: eye that meets inclusion criteria. If both eyes meet all inclusion and exclusion criteria, the eye with the lower BCVA at Screening will be selected as the study eye. If both eyes meet all inclusion criteria and have identical BCVA at Screening, selection of the study eye will be at the investigator's discretion.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

Full-analysis set (FAS): The FAS consisted of all participants who were randomly assigned to receive double-masked study drug and who have received at least 1 dose of study drug. All analyses using the FAS grouped participants according to randomly assigned treatment.

Arm/Group Title	Placebo	MT-0814 Low Dose	MT-0814 High Dose
Arm/Group Description	Placebo: Placebo manufactured to mimic MT-0814	MT-0814 plus placebo MT-0814: Randomly assigned dose Placebo: Placebo manufactured to mimic MT-0814	MT-0814: Randomly assigned dose
Measure Participants	3	5	5
Least Squares Mean (95% Confidence Interval) [mm]	-0.0053	-0.0016	0.0026

Adverse Events

Time Frame	16 weeks
Adverse Event Reporting Description	Adverse events were analyzed in terms of Treatment-Emergent Adverse Events (TEAEs), which were defined as any event not present before exposure to study drug or any event already present that worsened in either intensity or frequency after exposure to the study drug.
Arm/Group Title	Placebo		MT-0814 Low Dose		MT-0814 High Dose
Arm/Group Description	Placebo: Placebo manufactured to mimic MT-0814		MT-0814 plus placebo MT-0814: Randomly assigned dose Placebo: Placebo manufactured to mimic MT-0814		MT-0814: Randomly assigned dose
All Cause Mortality
	Placebo		MT-0814 Low Dose		MT-0814 High Dose
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/5 (0%)		0/5 (0%)
Serious Adverse Events
	Placebo		MT-0814 Low Dose		MT-0814 High Dose
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/5 (0%)		2/5 (40%)
Investigations
Hepatic enzyme increased	0/3 (0%)	0	0/5 (0%)	0	1/5 (20%)	1
Liver function test increased	0/3 (0%)	0	0/5 (0%)	0	1/5 (20%)	1
Other (Not Including Serious) Adverse Events
	Placebo		MT-0814 Low Dose		MT-0814 High Dose
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/3 (100%)		5/5 (100%)		3/5 (60%)
Cardiac disorders
Tachycardia	0/3 (0%)	0	1/5 (20%)	2	0/5 (0%)	0
Mitral valve prolapse	0/3 (0%)	0	1/5 (20%)	1	0/5 (0%)	0
Arrhythmia	0/3 (0%)	0	0/5 (0%)	0	1/5 (20%)	1
Eye disorders
Cataract nuclear	1/3 (33.3%)	2	0/5 (0%)	0	0/5 (0%)	0
Eye pain	1/3 (33.3%)	1	0/5 (0%)	0	0/5 (0%)	0
Neovascular age-related macular degneration	0/3 (0%)	0	1/5 (20%)	1	1/5 (20%)	1
Retinal haemorrhage	0/3 (0%)	0	1/5 (20%)	1	0/5 (0%)	0
Subretinal fluid	0/3 (0%)	0	1/5 (20%)	1	0/5 (0%)	0
Dry age-related macular degeneration	0/3 (0%)	0	0/5 (0%)	0	1/5 (20%)	1
Gastrointestinal disorders
Nausea	1/3 (33.3%)	1	0/5 (0%)	0	1/5 (20%)	3
Vomiting	1/3 (33.3%)	1	0/5 (0%)	0	0/5 (0%)	0
Faeces discoloured	0/3 (0%)	0	1/5 (20%)	1	0/5 (0%)	0
Abdominal pain	0/3 (0%)	0	0/5 (0%)	0	1/5 (20%)	1
General disorders
Fatigue	1/3 (33.3%)	1	1/5 (20%)	1	1/5 (20%)	1
Investigations
Gamma-glutamyltransferase increased	1/3 (33.3%)	1	0/5 (0%)	0	1/5 (20%)	1
Alanine aminotransferase increased	0/3 (0%)	0	1/5 (20%)	2	1/5 (20%)	2
Aspartate aminotransferase increased	0/3 (0%)	0	1/5 (20%)	1	1/5 (20%)	2
C-reactive protein increased	0/3 (0%)	0	0/5 (0%)	0	1/5 (20%)	1
High density lipoprotein decreased	0/3 (0%)	0	0/5 (0%)	0	1/5 (20%)	1
Musculoskeletal and connective tissue disorders
Spinal osteoarthritis	0/3 (0%)	0	1/5 (20%)	1	0/5 (0%)	0
Nervous system disorders
Migraine	1/3 (33.3%)	1	0/5 (0%)	0	0/5 (0%)	0
Headache	1/3 (33.3%)	1	0/5 (0%)	0	0/5 (0%)	0
Tension headach	0/3 (0%)	0	0/5 (0%)	0	1/5 (20%)	1
Respiratory, thoracic and mediastinal disorders
Nasal congestion	0/3 (0%)	0	1/5 (20%)	1	0/5 (0%)	0

Limitations/Caveats

All of the efficacy and safety measurements applied in this study are widely used and generally recognized as reliable, accurate, and relevant.

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.