Trial Outcomes & Findings for Pilot Study of X-82 in Patients With Wet AMD (NCT NCT01674569)

Last Updated: 2018-08-07

Results Overview

The best corrected visual acuity by the Early Treatment Diabetic Retinopathy Study (ETDRS) method was determined at baseline and at various times during the study. The ETDRS method records the number of letters of decreasing size on a chart that a subject can read from a defiend distance. During the study the ETDRS visual acuity was used to monitor the need for rescue therapy. The primary endpoint of the study was the change from baseline visual ETDRS visual acuity at 6 months. It was calculated by subtracting the baseline visual acuity from the visual acuity at 6 months for each individual subject. A positive change from baseline indicates improvement in visual acuity.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

35 participants

Primary outcome timeframe

6 months

Results posted on

2018-08-07

Participant Flow

Subjects with wet age related macular degeneration were enrolled at 5 US retinal clinics between November 2012 and March 2015

110 subjects were screened for entry into the study. 52 did not meet inclusion criteria, 19 declined to participate and 4 were excluded for other reasons

Participant milestones

Participant milestones
Measure	50 mg X82 Alternate Days Participants were assigned to 50 mg X-82 on alternate days for 24 weeks. After treatment discontinuation subjects were followed for an additional 4 weeks.	50 mg X82 QD Participants were assigned to 50 mg X-82 QD for 24 weeks. After treatment discontinuation subjects were followed for an additional 4 weeks.	100 mg X82 on Alternate Days Participants were assigned to 100 mg X-82 on alternate days for 24 weeks. After treatment discontinuation subjects were followed for an additional 4 weeks.	100 mg X82 QD Participants were assigned to 100 mg X-82 QD for 24 weeks. After treatment discontinuation subjects were followed for an additional 4 weeks.	200 mg X82 QD Participants were assigned to 200 mg X-82 QD for 24 weeks. After treatment discontinuation subjects were followed for an additional 4 weeks.	300 mg X82 QD Participants were assigned to 300 mg X-82 QD for 24 weeks. After treatment discontinuation subjects were followed for an additional 4 weeks.
Overall Study STARTED	3	8	4	10	7	3
Overall Study COMPLETED	3	5	2	9	5	1
Overall Study NOT COMPLETED	0	3	2	1	2	2

Reasons for withdrawal

Reasons for withdrawal
Measure	50 mg X82 QD Participants were assigned to 50 mg X-82 QD for 24 weeks. After treatment discontinuation subjects were followed for an additional 4 weeks.	100 mg X82 on Alternate Days Participants were assigned to 100 mg X-82 on alternate days for 24 weeks. After treatment discontinuation subjects were followed for an additional 4 weeks.	100 mg X82 QD Participants were assigned to 100 mg X-82 QD for 24 weeks. After treatment discontinuation subjects were followed for an additional 4 weeks.	200 mg X82 QD Participants were assigned to 200 mg X-82 QD for 24 weeks. After treatment discontinuation subjects were followed for an additional 4 weeks.	300 mg X82 QD Participants were assigned to 300 mg X-82 QD for 24 weeks. After treatment discontinuation subjects were followed for an additional 4 weeks.
Overall Study Adverse Event	2	0	1	2	2
Overall Study Protocol Violation	1	1	0	0	0
Overall Study Withdrawal by Subject	0	1	0	0	0

Baseline Characteristics

Pilot Study of X-82 in Patients With Wet AMD

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dose Escalation of X-82 and Ranibizumab Rescue n=35 Participants Groups of participants were assigned to 1 of 6 X-82 doses over 24weeks,with an additional 4 weeks for follow-up. The dose escalated from one level to the next in the absence of any dose-limiting toxicity (DLT) defined as a drug-related safety event during the first 2 weeks of treatment that was severe enough to require removal of the participant from the study. The escalating X82 oral dose regimens were 50 mg alternate days, 50 mg daily, 100 mg alternate days, 100mg daily, 200mg daily, and 300mg daily.
Age, Continuous	76.8 years STANDARD_DEVIATION 8.5 • n=5 Participants
Sex: Female, Male Female	19 Participants n=5 Participants
Sex: Female, Male Male	16 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants
Race (NIH/OMB) White	33 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	35 participants n=5 Participants
Best corrected visual acuity	62.4 Number of letters STANDARD_DEVIATION 12.6 • n=5 Participants

PRIMARY outcome

Timeframe: 6 months

Population: The mean and standard deviation was calculated for all subjects who completed 6 months of treatment with oral X82

Outcome measures

Outcome measures
Measure	All Completers n=25 Participants All subjects who successfully completed 6 months of treatment with oral X82
Change From Baseline Visual Acuity at 6 Months	3.8 number of letters Standard Deviation 9.6

Adverse Events

Dose Escalation of X-82 and Ranibizumab Rescue

Serious events: 3 serious events

Other events: 28 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Dose Escalation of X-82 and Ranibizumab Rescue n=35 participants at risk Groups of participants were assigned to 1 of 6 X-82 doses over 24 weeks,with an additional 4 weeks for follow-up. The dose escalated from one level to the next in the absence of any dose-limiting toxicity (DLT) defined as a drug-related safety event during the first 2 weeks of treatment that was severe enough to require removal of the participant from the study. The escalating X82 oral dose regimens were 50 mg alternate days, 50 mg daily, 100 mg alternate days, 100mg daily, 200mg daily, and 300mg daily.
Cardiac disorders Chest pain	2.9% 1/35 • Number of events 1 • Adverse events were recorded for the duration of the study beginning at participant randomization and continuing till participant completion of the study. The participation of individual subjects in the study ranged from 1-7 months. Since the sample size for each dose group of X82 was limited, the frequency of adverse events are reported for all patients enrolled in the study.
Renal and urinary disorders Acute renal failure	2.9% 1/35 • Number of events 1 • Adverse events were recorded for the duration of the study beginning at participant randomization and continuing till participant completion of the study. The participation of individual subjects in the study ranged from 1-7 months. Since the sample size for each dose group of X82 was limited, the frequency of adverse events are reported for all patients enrolled in the study.
Cardiac disorders Congestive heart failure	2.9% 1/35 • Number of events 1 • Adverse events were recorded for the duration of the study beginning at participant randomization and continuing till participant completion of the study. The participation of individual subjects in the study ranged from 1-7 months. Since the sample size for each dose group of X82 was limited, the frequency of adverse events are reported for all patients enrolled in the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) multiple myeloma	2.9% 1/35 • Number of events 1 • Adverse events were recorded for the duration of the study beginning at participant randomization and continuing till participant completion of the study. The participation of individual subjects in the study ranged from 1-7 months. Since the sample size for each dose group of X82 was limited, the frequency of adverse events are reported for all patients enrolled in the study.

Other adverse events

Other adverse events
Measure	Dose Escalation of X-82 and Ranibizumab Rescue n=35 participants at risk Groups of participants were assigned to 1 of 6 X-82 doses over 24 weeks,with an additional 4 weeks for follow-up. The dose escalated from one level to the next in the absence of any dose-limiting toxicity (DLT) defined as a drug-related safety event during the first 2 weeks of treatment that was severe enough to require removal of the participant from the study. The escalating X82 oral dose regimens were 50 mg alternate days, 50 mg daily, 100 mg alternate days, 100mg daily, 200mg daily, and 300mg daily.
Gastrointestinal disorders Diarrhoea	14.3% 5/35 • Adverse events were recorded for the duration of the study beginning at participant randomization and continuing till participant completion of the study. The participation of individual subjects in the study ranged from 1-7 months. Since the sample size for each dose group of X82 was limited, the frequency of adverse events are reported for all patients enrolled in the study.
Gastrointestinal disorders Nausea	14.3% 5/35 • Adverse events were recorded for the duration of the study beginning at participant randomization and continuing till participant completion of the study. The participation of individual subjects in the study ranged from 1-7 months. Since the sample size for each dose group of X82 was limited, the frequency of adverse events are reported for all patients enrolled in the study.
Gastrointestinal disorders Gastrointestinal reflux	5.7% 2/35 • Adverse events were recorded for the duration of the study beginning at participant randomization and continuing till participant completion of the study. The participation of individual subjects in the study ranged from 1-7 months. Since the sample size for each dose group of X82 was limited, the frequency of adverse events are reported for all patients enrolled in the study.
Gastrointestinal disorders Vomiting	5.7% 2/35 • Adverse events were recorded for the duration of the study beginning at participant randomization and continuing till participant completion of the study. The participation of individual subjects in the study ranged from 1-7 months. Since the sample size for each dose group of X82 was limited, the frequency of adverse events are reported for all patients enrolled in the study.
Infections and infestations Urinary tract infection	14.3% 5/35 • Adverse events were recorded for the duration of the study beginning at participant randomization and continuing till participant completion of the study. The participation of individual subjects in the study ranged from 1-7 months. Since the sample size for each dose group of X82 was limited, the frequency of adverse events are reported for all patients enrolled in the study.
General disorders Fatigue	14.3% 5/35 • Adverse events were recorded for the duration of the study beginning at participant randomization and continuing till participant completion of the study. The participation of individual subjects in the study ranged from 1-7 months. Since the sample size for each dose group of X82 was limited, the frequency of adverse events are reported for all patients enrolled in the study.
Infections and infestations Sinusitis	11.4% 4/35 • Adverse events were recorded for the duration of the study beginning at participant randomization and continuing till participant completion of the study. The participation of individual subjects in the study ranged from 1-7 months. Since the sample size for each dose group of X82 was limited, the frequency of adverse events are reported for all patients enrolled in the study.
Infections and infestations Nasopharyngitis	5.7% 2/35 • Adverse events were recorded for the duration of the study beginning at participant randomization and continuing till participant completion of the study. The participation of individual subjects in the study ranged from 1-7 months. Since the sample size for each dose group of X82 was limited, the frequency of adverse events are reported for all patients enrolled in the study.
Hepatobiliary disorders Alanine amino transferase elevation	8.6% 3/35 • Adverse events were recorded for the duration of the study beginning at participant randomization and continuing till participant completion of the study. The participation of individual subjects in the study ranged from 1-7 months. Since the sample size for each dose group of X82 was limited, the frequency of adverse events are reported for all patients enrolled in the study.
Hepatobiliary disorders Aspartate amino transferase elevation	8.6% 3/35 • Adverse events were recorded for the duration of the study beginning at participant randomization and continuing till participant completion of the study. The participation of individual subjects in the study ranged from 1-7 months. Since the sample size for each dose group of X82 was limited, the frequency of adverse events are reported for all patients enrolled in the study.
General disorders decrease body weight	5.7% 2/35 • Adverse events were recorded for the duration of the study beginning at participant randomization and continuing till participant completion of the study. The participation of individual subjects in the study ranged from 1-7 months. Since the sample size for each dose group of X82 was limited, the frequency of adverse events are reported for all patients enrolled in the study.
Musculoskeletal and connective tissue disorders muscle spasma	8.6% 3/35 • Adverse events were recorded for the duration of the study beginning at participant randomization and continuing till participant completion of the study. The participation of individual subjects in the study ranged from 1-7 months. Since the sample size for each dose group of X82 was limited, the frequency of adverse events are reported for all patients enrolled in the study.
Musculoskeletal and connective tissue disorders arthritis	5.7% 2/35 • Adverse events were recorded for the duration of the study beginning at participant randomization and continuing till participant completion of the study. The participation of individual subjects in the study ranged from 1-7 months. Since the sample size for each dose group of X82 was limited, the frequency of adverse events are reported for all patients enrolled in the study.
General disorders Headache	11.4% 4/35 • Adverse events were recorded for the duration of the study beginning at participant randomization and continuing till participant completion of the study. The participation of individual subjects in the study ranged from 1-7 months. Since the sample size for each dose group of X82 was limited, the frequency of adverse events are reported for all patients enrolled in the study.
General disorders Dizziness	5.7% 2/35 • Adverse events were recorded for the duration of the study beginning at participant randomization and continuing till participant completion of the study. The participation of individual subjects in the study ranged from 1-7 months. Since the sample size for each dose group of X82 was limited, the frequency of adverse events are reported for all patients enrolled in the study.
Gastrointestinal disorders Dysgeusia	5.7% 2/35 • Adverse events were recorded for the duration of the study beginning at participant randomization and continuing till participant completion of the study. The participation of individual subjects in the study ranged from 1-7 months. Since the sample size for each dose group of X82 was limited, the frequency of adverse events are reported for all patients enrolled in the study.
Cardiac disorders hypertension	5.7% 2/35 • Adverse events were recorded for the duration of the study beginning at participant randomization and continuing till participant completion of the study. The participation of individual subjects in the study ranged from 1-7 months. Since the sample size for each dose group of X82 was limited, the frequency of adverse events are reported for all patients enrolled in the study.

Additional Information

Sr Vice President, Development

Tyrogenex, Inc

Phone: 240-403-7153

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place