Trial Outcomes & Findings for A 4-Week Safety Study of Oral ELND005 in Young Adults With Down Syndrome Without Dementia (NCT NCT01791725)

Last Updated: 2019-11-04

Results Overview

For all AE summaries, if a patient had more than one AE within a preferred term, the patient was counted only once, at the maximum severity and with the closest relationship to study drug. If a patient had more than one AE within a SOC, the subject was similarly counted only once when reporting results for that SOC.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

23 participants

Primary outcome timeframe

4 weeks

Results posted on

2019-11-04

Participant Flow

Participant milestones

Participant milestones
Measure	ELND005 BID ELND005 250 mg BID ELND005	ELND005 QD ELND005 250 mg QD ELND005	Placebo Placebo BID Placebo
Overall Study STARTED	12	5	6
Overall Study COMPLETED	12	4	6
Overall Study NOT COMPLETED	0	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	ELND005 BID ELND005 250 mg BID ELND005	ELND005 QD ELND005 250 mg QD ELND005	Placebo Placebo BID Placebo
Overall Study Withdrawal by Subject	0	1	0

Baseline Characteristics

A 4-Week Safety Study of Oral ELND005 in Young Adults With Down Syndrome Without Dementia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	ELND005 BID n=12 Participants ELND005 250 mg BID ELND005	ELND005 QD n=5 Participants ELND005 250 mg QD ELND005	Placebo n=6 Participants Placebo BID Placebo	Total n=23 Participants Total of all reporting groups
Age, Continuous	26.3 years STANDARD_DEVIATION 7.43 • n=99 Participants	27.8 years STANDARD_DEVIATION 4.03 • n=107 Participants	30.0 years STANDARD_DEVIATION 5.93 • n=206 Participants	27.6 years STANDARD_DEVIATION 6.49 • n=7 Participants
Sex: Female, Male Female	3 Participants n=99 Participants	3 Participants n=107 Participants	3 Participants n=206 Participants	9 Participants n=7 Participants
Sex: Female, Male Male	9 Participants n=99 Participants	2 Participants n=107 Participants	3 Participants n=206 Participants	14 Participants n=7 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=99 Participants	0 Participants n=107 Participants	1 Participants n=206 Participants	2 Participants n=7 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	11 Participants n=99 Participants	5 Participants n=107 Participants	5 Participants n=206 Participants	21 Participants n=7 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Race (NIH/OMB) Asian	1 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	1 Participants n=7 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Race (NIH/OMB) Black or African American	1 Participants n=99 Participants	1 Participants n=107 Participants	0 Participants n=206 Participants	2 Participants n=7 Participants
Race (NIH/OMB) White	10 Participants n=99 Participants	4 Participants n=107 Participants	6 Participants n=206 Participants	20 Participants n=7 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Region of Enrollment United States	12 participants n=99 Participants	5 participants n=107 Participants	6 participants n=206 Participants	23 participants n=7 Participants
IQ Score	50.6 units on a scale STANDARD_DEVIATION 13.81 • n=99 Participants	63.3 units on a scale STANDARD_DEVIATION 19.62 • n=107 Participants	55.8 units on a scale STANDARD_DEVIATION 6.65 • n=206 Participants	54.3 units on a scale STANDARD_DEVIATION 13.75 • n=7 Participants

PRIMARY outcome

Timeframe: 4 weeks

Outcome measures

Outcome measures
Measure	ELND005 BID n=12 Participants ELND005 250 mg BID ELND005	ELND005 QD n=5 Participants ELND005 250 mg QD ELND005	Placebo n=6 Participants Placebo BID Placebo
Incidence of Adverse Events (TEAEs)	5 participants	2 participants	0 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and 4 weeks

Subjects with Abnormal Neurological Examination Results

Outcome measures

Outcome measures
Measure	ELND005 BID n=12 Participants ELND005 250 mg BID ELND005	ELND005 QD n=4 Participants ELND005 250 mg QD ELND005	Placebo n=6 Participants Placebo BID Placebo
Changes From Baseline in Abnormal Neurological Examination Results Baseline	4 participants	1 participants	3 participants
Changes From Baseline in Abnormal Neurological Examination Results Week 4	4 participants	1 participants	3 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and 4 Weeks

Mean Plasma ELND005 Concentrations- Cmax

Outcome measures

Outcome measures
Measure	ELND005 BID n=12 Participants ELND005 250 mg BID ELND005	ELND005 QD n=4 Participants ELND005 250 mg QD ELND005	Placebo n=6 Participants Placebo BID Placebo
Pharmacokinetic Assessment Mean Cmax, First Dose, Day 0	1.68 μg/mL Standard Deviation 0.90	2.61 μg/mL Standard Deviation 0.62	0 μg/mL Standard Deviation 0
Pharmacokinetic Assessment Mean Cmax, Last Dose, Day 28	6.33 μg/mL Standard Deviation 1.95	4.48 μg/mL Standard Deviation 1.13	0 μg/mL Standard Deviation 0

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and 4 Weeks

Rapid Assessment for Development Disabilities (RADD) The RADD test was developed from the low-difficulty items from published intelligence tests (Walsh et al 2007). It was specifically developed for evaluation of individuals with intellectual disabilities and developmental disabilities. It is a validated and reliable cognitive screening instrument that can be rapidly administered. The RADD is composed of 76 items. Each item is scored as 0 (incorrect) or 1 (correct).The test assesses a wide range of functional abilities including receptive and expressive language, orientation, registration, recall, attention, self identification, motor skills, imitation, abstract reasoning, number skills, comprehension and short-term memory to give a total score. Scores are from 0 to 76. A higher total score is correlated with a higher Cognitive Impairment level.

Outcome measures

Outcome measures
Measure	ELND005 BID n=12 Participants ELND005 250 mg BID ELND005	ELND005 QD n=4 Participants ELND005 250 mg QD ELND005	Placebo n=6 Participants Placebo BID Placebo
Cognitive Outcome (RADD Total Score) Day 0	58.7 units on a scale Standard Deviation 10.2	58.0 units on a scale Standard Deviation 15.6	62.2 units on a scale Standard Deviation 9.8
Cognitive Outcome (RADD Total Score) Week 4	59.1 units on a scale Standard Deviation 11.5	64.3 units on a scale Standard Deviation 13.5	62.8 units on a scale Standard Deviation 10.3

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and 4 weeks

Population: Subjects with NPI Score ≥1 at baseline

The Neuropsychiatric Inventory(NPI) (Cummings et al 1994) is a behavioral measure that assesses psychopathology in dementia patients. The NPI was administered at the Baseline Visit (Day 1) and at Day 28 (EOS) or ET. A decrease in score shows an improvement in symptoms.

Outcome measures

Outcome measures
Measure	ELND005 BID n=8 Participants ELND005 250 mg BID ELND005	ELND005 QD n=4 Participants ELND005 250 mg QD ELND005	Placebo n=3 Participants Placebo BID Placebo
Improvement in NPI Total Scores in Subjects With NPI Score ≥1 at Baseline Baseline	7 participants	0 participants	1 participants

Adverse Events

ELND005 BID

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

ELND005 QD

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	ELND005 BID n=12 participants at risk ELND005 250 mg BID ELND005	ELND005 QD n=5 participants at risk ELND005 250 mg QD ELND005	Placebo n=6 participants at risk Placebo BID Placebo
Cardiac disorders Bradycardia	8.3% 1/12 • Adverse events were recorded for each patient, starting from the time the consent form was signed until completion of the study.	0.00% 0/5 • Adverse events were recorded for each patient, starting from the time the consent form was signed until completion of the study.	0.00% 0/6 • Adverse events were recorded for each patient, starting from the time the consent form was signed until completion of the study.
Gastrointestinal disorders Diarrhoea	8.3% 1/12 • Adverse events were recorded for each patient, starting from the time the consent form was signed until completion of the study.	0.00% 0/5 • Adverse events were recorded for each patient, starting from the time the consent form was signed until completion of the study.	0.00% 0/6 • Adverse events were recorded for each patient, starting from the time the consent form was signed until completion of the study.
General disorders Catheter Site Pain	0.00% 0/12 • Adverse events were recorded for each patient, starting from the time the consent form was signed until completion of the study.	20.0% 1/5 • Adverse events were recorded for each patient, starting from the time the consent form was signed until completion of the study.	0.00% 0/6 • Adverse events were recorded for each patient, starting from the time the consent form was signed until completion of the study.
Immune system disorders Seasonal Allergy	8.3% 1/12 • Adverse events were recorded for each patient, starting from the time the consent form was signed until completion of the study.	0.00% 0/5 • Adverse events were recorded for each patient, starting from the time the consent form was signed until completion of the study.	0.00% 0/6 • Adverse events were recorded for each patient, starting from the time the consent form was signed until completion of the study.
Injury, poisoning and procedural complications Muscle Strain	0.00% 0/12 • Adverse events were recorded for each patient, starting from the time the consent form was signed until completion of the study.	20.0% 1/5 • Adverse events were recorded for each patient, starting from the time the consent form was signed until completion of the study.	0.00% 0/6 • Adverse events were recorded for each patient, starting from the time the consent form was signed until completion of the study.
Investigations Electrocardiogram abnormal	0.00% 0/12 • Adverse events were recorded for each patient, starting from the time the consent form was signed until completion of the study.	20.0% 1/5 • Adverse events were recorded for each patient, starting from the time the consent form was signed until completion of the study.	0.00% 0/6 • Adverse events were recorded for each patient, starting from the time the consent form was signed until completion of the study.
Nervous system disorders Resting Tremor	8.3% 1/12 • Adverse events were recorded for each patient, starting from the time the consent form was signed until completion of the study.	0.00% 0/5 • Adverse events were recorded for each patient, starting from the time the consent form was signed until completion of the study.	0.00% 0/6 • Adverse events were recorded for each patient, starting from the time the consent form was signed until completion of the study.
Psychiatric disorders Anger	0.00% 0/12 • Adverse events were recorded for each patient, starting from the time the consent form was signed until completion of the study.	20.0% 1/5 • Adverse events were recorded for each patient, starting from the time the consent form was signed until completion of the study.	0.00% 0/6 • Adverse events were recorded for each patient, starting from the time the consent form was signed until completion of the study.
Skin and subcutaneous tissue disorders Pseudofolliculitis barbae	8.3% 1/12 • Adverse events were recorded for each patient, starting from the time the consent form was signed until completion of the study.	0.00% 0/5 • Adverse events were recorded for each patient, starting from the time the consent form was signed until completion of the study.	0.00% 0/6 • Adverse events were recorded for each patient, starting from the time the consent form was signed until completion of the study.
Gastrointestinal disorders Oral Disorder	8.3% 1/12 • Adverse events were recorded for each patient, starting from the time the consent form was signed until completion of the study.	0.00% 0/5 • Adverse events were recorded for each patient, starting from the time the consent form was signed until completion of the study.	0.00% 0/6 • Adverse events were recorded for each patient, starting from the time the consent form was signed until completion of the study.
Nervous system disorders Restless leg syndrome	8.3% 1/12 • Adverse events were recorded for each patient, starting from the time the consent form was signed until completion of the study.	0.00% 0/5 • Adverse events were recorded for each patient, starting from the time the consent form was signed until completion of the study.	0.00% 0/6 • Adverse events were recorded for each patient, starting from the time the consent form was signed until completion of the study.

Additional Information

Aleksandra Pastrak,MD, PhD, VP of Clinical Development and Medical Officer

Transition Therapeutics Ireland Limited

Phone: +1 416 263 1227

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60