Trial Outcomes & Findings for Pharmacological Treatment of Rett Syndrome With Glatiramer Acetate (Copaxone) (NCT NCT02153723)

NCT ID: NCT02153723

Last Updated: 2018-11-05

Results Overview

To perform quantitative gait assessments a computerized walkway (457 × 90.2 × 0.64cm) with embedded pressure sensors (GAIT Rite system) was used. Subjects walked on the walkway for two trials, while wearing comfortable footwear.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

10 participants

Primary outcome timeframe

Baseline and Final week of treatment (week 32)

Results posted on

2018-11-05

Participant Flow

All participants were recruited between Aug 2014-Jan 2015, from the population treated at the Rett Center at Montefiore. Of 11 screened subjects, 10 met the inclusion/exclusion criteria and completed the trial. One patient was excluded due to prolonged QTc. Data analysis was performed after the first 10 participants completed the study.

Participant milestones

Participant milestones
Measure
Copaxone
Dose escalation: Study drug will be administered once a week for 4 weeks, twice a week for 4 weeks and daily for 24 weeks. Drug is administered as a subcutaneous injection. Glatiramer Acetate
Overall Study
STARTED
10
Overall Study
COMPLETED
10
Overall Study
NOT COMPLETED
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Pharmacological Treatment of Rett Syndrome With Glatiramer Acetate (Copaxone)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Copaxone
n=10 Participants
Dose escalation: Study drug will be administered once a week for 4 weeks, twice a week for 4 weeks and daily for 24 weeks. Drug is administered as a subcutaneous injection. Glatiramer Acetate
Age, Categorical
<=18 years
9 Participants
n=5 Participants
Age, Categorical
Between 18 and 65 years
1 Participants
n=5 Participants
Age, Categorical
>=65 years
0 Participants
n=5 Participants
Sex: Female, Male
Female
10 Participants
n=5 Participants
Sex: Female, Male
Male
0 Participants
n=5 Participants
Region of Enrollment
United States
10 participants
n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Final week of treatment (week 32)

Population: All 10 patients were females with genetically confirmed Rett syndrome. All were at least 10 years old and ambulatory (walking without assistance at the time of their enrollment).

To perform quantitative gait assessments a computerized walkway (457 × 90.2 × 0.64cm) with embedded pressure sensors (GAIT Rite system) was used. Subjects walked on the walkway for two trials, while wearing comfortable footwear.

Outcome measures

Outcome measures
Measure
Copaxone
n=10 Participants
Dose escalation: Study drug will be administered once a week for 4 weeks, twice a week for 4 weeks and daily for 24 weeks. Drug is administered as a subcutaneous injection. Glatiramer Acetate
Gait Velocity as Measured by GAITRite System
Baseline
62.7 cm/sec
Interval 42.3 to 103.2
Gait Velocity as Measured by GAITRite System
Final week of treatment (week 32)
84.3 cm/sec
Interval 58.1 to 119.3

SECONDARY outcome

Timeframe: Baseline and during final week of treatment (week 32)

Population: One of the 10 enrolled patients experienced panic attack during the respiratory function testing so that session was discontinued. This left 9 participants for final analysis.

Breath hold index is defined as number of breath holds/hour. Respirations were monitored with sleep monitoring equipment during the daytime at the polysomnography laboratory with additional oronasal airflow, electromyography (EMG), EEG and video monitoring to confirm wakefulness during the period of study.

Outcome measures

Outcome measures
Measure
Copaxone
n=9 Participants
Dose escalation: Study drug will be administered once a week for 4 weeks, twice a week for 4 weeks and daily for 24 weeks. Drug is administered as a subcutaneous injection. Glatiramer Acetate
Breath Hold Index (Number of Breath Holds Per Hour; Assessed in the Sleep Monitoring Lab)
Baseline
3.8 number of breath holds/hour
Interval 2.3 to 7.3
Breath Hold Index (Number of Breath Holds Per Hour; Assessed in the Sleep Monitoring Lab)
Final week of treatment (week 32)
1.6 number of breath holds/hour
Interval 0.3 to 2.0

SECONDARY outcome

Timeframe: Baseline and Final week of treatment (week 32)

Population: One of the 10 enrolled patients experienced panic attack during the respiratory function testing so that session was discontinued. This left 9 participants for final analysis.

Breath Hold Time is defined as percentage of time spent holding the breath in a specific time unit. It is measured by a standard medical technique where belts are placed on the chest and abdomen to record movement and sensors are used to record nasal flow. Wake respiration was monitored with sleep monitoring equipment during the daytime at the polysomnography laboratory with additional oronasal airflow, EMG, EEG and video monitoring to confirm wakefulness during the period of study.

Outcome measures

Outcome measures
Measure
Copaxone
n=9 Participants
Dose escalation: Study drug will be administered once a week for 4 weeks, twice a week for 4 weeks and daily for 24 weeks. Drug is administered as a subcutaneous injection. Glatiramer Acetate
Breath Hold Time (Assessed in the Sleep Monitoring Lab)
Baseline
1.8 percentage of time
Interval 0.8 to 2.3
Breath Hold Time (Assessed in the Sleep Monitoring Lab)
Final week of treatment (week 32)
0.4 percentage of time
Interval 0.1 to 0.8

SECONDARY outcome

Timeframe: Baseline and Final week of treatment (week 32)

Population: Only 7 of the 10 recruited participants were able to complete the cognitive assessment. The remaining 3 participants could not be tested due to technical reasons.

Eye-tracking is considered an indication of visual memory. Eye-tracking data was recorded at 300 Hz sampling rate using a Tobii T300 computer (Tobii Technology, Danderyd, Sweden). The actual data given by the computer represents the percentage of time spent looking at a novel visual target - this is called the novelty score. Visual memory, as indexed by the novelty score, is the percentage of time spent looking at a novel target during the test ("visual paired comparison paradigm"). Duration of testing was 2 minutes.

Outcome measures

Outcome measures
Measure
Copaxone
n=7 Participants
Dose escalation: Study drug will be administered once a week for 4 weeks, twice a week for 4 weeks and daily for 24 weeks. Drug is administered as a subcutaneous injection. Glatiramer Acetate
Visual Memory Novelty Score as Assessed by TX300 Tobii Computer.
Baseline
42.4 percentage of time
Interval 39.5 to 61.0
Visual Memory Novelty Score as Assessed by TX300 Tobii Computer.
Final week of treatment (week 32)
62.4 percentage of time
Interval 55.7 to 65.8

SECONDARY outcome

Timeframe: Baseline and Final week of treatment (week 32)

Population: Only 7 of the 10 recruited participants were able to complete the cognitive assessment. The remaining 3 participants could not be tested due to technical reasons.

Visual attention is indexed by duration and number of fixations on novel target on testing. The standard method of assessing visual attention in neuropsychology is by measuring: A)number of fixations (how many times the subject looks at each of the 2 visual targets). The higher number of fixations, the more attentive the subject to that visual target. B) duration of fixations in seconds (the longer the fixation the more attentive). Duration of fixations correlates with intelligence: the smarter the person is the shorter his fixations are. Eye-tracking data was recorded at 300 Hz sampling rate using a Tobii T300 (Tobii Technology AB, Danderyd, Sweden). The measured index is called the Novelty Score which indicates the percentage of time spent looking at novel visual target. Duration of testing session was 2 minutes.

Outcome measures

Outcome measures
Measure
Copaxone
n=7 Participants
Dose escalation: Study drug will be administered once a week for 4 weeks, twice a week for 4 weeks and daily for 24 weeks. Drug is administered as a subcutaneous injection. Glatiramer Acetate
Visual Attention (Number of Fixations) Assessed by Eye-tracking TX300 Tobii Computer.
Baseline
19.4 number of fixations
Interval 8.0 to 20.8
Visual Attention (Number of Fixations) Assessed by Eye-tracking TX300 Tobii Computer.
Final week of treatment (week 32)
16.2 number of fixations
Interval 11.0 to 27.4

SECONDARY outcome

Timeframe: Baseline and Final week of treatment (week 32)

Population: Only 7 of the 10 recruited participants were able to complete the cognitive assessment. The remaining 3 participants could not be tested due to technical reasons.

The standard method of assessing visual attention in neuropsychology is by measuring: A)number of fixations (how many times the subject looks at each of the 2 visual targets). The higher number of fixations, the more attentive the subject to that visual target. B) duration of fixations in seconds (the longer the fixation the more attentive). Duration of fixations correlates with intelligence: the smarter the person is the shorter his fixations are. Eye-tracking data was recorded at 300 Hz sampling rate using a Tobii T300 (Tobii Technology AB, Danderyd, Sweden). The measured index is called the Novelty Score which indicates the percentage of time spent looking at novel visual target. Visual attention is indexed by number of fixations on novel target on test. Duration of testing session was 2 minutes.

Outcome measures

Outcome measures
Measure
Copaxone
n=7 Participants
Dose escalation: Study drug will be administered once a week for 4 weeks, twice a week for 4 weeks and daily for 24 weeks. Drug is administered as a subcutaneous injection. Glatiramer Acetate
Visual Attention (Fixation Length) Assessed by Eye-tracking TX300 Tobii Computer.
Baseline
0.46 seconds
Interval 0.26 to 0.64
Visual Attention (Fixation Length) Assessed by Eye-tracking TX300 Tobii Computer.
Final week of treatment (week 32)
0.35 seconds
Interval 0.18 to 0.46

Adverse Events

Copaxone

Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Copaxone
n=10 participants at risk
Dose escalation: Study drug will be administered once a week for 4 weeks, twice a week for 4 weeks and daily for 24 weeks. Drug is administered as a subcutaneous injection. Glatiramer Acetate
Musculoskeletal and connective tissue disorders
laboratory result (elevated CPK) without clinical correlate, transitory
10.0%
1/10 • Number of events 1

Additional Information

Aleksandra Djukic

Montefiore Medical Center

Phone: 718 920 4378

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place