Trial Outcomes & Findings for Treatment of Rett Syndrome With rhIGF-1 (Mecasermin [rDNA]Injection) (NCT NCT01253317)
NCT ID: NCT01253317
Last Updated: 2017-06-22
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
12 participants
Primary outcome timeframe
biweekly during the MAD and every five weeks during the OLE
Results posted on
2017-06-22
Participant Flow
Participant milestones
| Measure |
Open-label IGF-1 Treatment
Twelve girls with MECP2 mutations participated in the 4-week multiple ascending dose (MAD) period of open-label treatment with IGF-1 (mecasermin). The MAD focused on obtaining PK data, determining cerebrospinal fluid (CSF) penetration, evaluating safety and tolerability, and estimating feasibility of automated cardiorespiratory measures as biomarkers. Mecasermin was escalated over a 4-week period, beginning with twice daily injections of 40 mcg/kg the first week, 80 mcg/kg the second week, and 120 mcg/kg during the third and fourth weeks. CSF samples were obtained prior to initiating treatment and after completing the fourth week.
10 of these subjects went on to complete the open label extension (OLE). The OLE was designed to obtain additional information on safety, tolerability, and cardiorespiratory measures after 20-weeks of treatment, as well as preliminary data on neurologic and behavioral parameters. During the 20-week OLE subjects were evaluated every 5 weeks.
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|---|---|
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Overall Study
STARTED
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12
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Overall Study
COMPLETED
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10
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Overall Study
NOT COMPLETED
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2
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Reasons for withdrawal
| Measure |
Open-label IGF-1 Treatment
Twelve girls with MECP2 mutations participated in the 4-week multiple ascending dose (MAD) period of open-label treatment with IGF-1 (mecasermin). The MAD focused on obtaining PK data, determining cerebrospinal fluid (CSF) penetration, evaluating safety and tolerability, and estimating feasibility of automated cardiorespiratory measures as biomarkers. Mecasermin was escalated over a 4-week period, beginning with twice daily injections of 40 mcg/kg the first week, 80 mcg/kg the second week, and 120 mcg/kg during the third and fourth weeks. CSF samples were obtained prior to initiating treatment and after completing the fourth week.
10 of these subjects went on to complete the open label extension (OLE). The OLE was designed to obtain additional information on safety, tolerability, and cardiorespiratory measures after 20-weeks of treatment, as well as preliminary data on neurologic and behavioral parameters. During the 20-week OLE subjects were evaluated every 5 weeks.
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Overall Study
Adverse Event
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2
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Baseline Characteristics
Treatment of Rett Syndrome With rhIGF-1 (Mecasermin [rDNA]Injection)
Baseline characteristics by cohort
| Measure |
Open-label IGF-1 Treatment
n=12 Participants
Twelve girls with MECP2 mutations participated in the 4-week multiple ascending dose (MAD) period of open-label treatment with IGF-1 (mecasermin). The MAD focused on obtaining PK data, determining cerebrospinal fluid (CSF) penetration, evaluating safety and tolerability, and estimating feasibility of automated cardiorespiratory measures as biomarkers. Mecasermin was escalated over a 4-week period, beginning with twice daily injections of 40 mcg/kg the first week, 80 mcg/kg the second week, and 120 mcg/kg during the third and fourth weeks. CSF samples were obtained prior to initiating treatment and after completing the fourth week.
10 of these subjects went on to complete the open label extension (OLE). The OLE was designed to obtain additional information on safety, tolerability, and cardiorespiratory measures after 20-weeks of treatment, as well as preliminary data on neurologic and behavioral parameters. During the 20-week OLE subjects were evaluated every 5 weeks.
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|---|---|
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Age, Categorical
<=18 years
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12 Participants
n=5 Participants
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Age, Categorical
Between 18 and 65 years
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0 Participants
n=5 Participants
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Age, Categorical
>=65 years
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0 Participants
n=5 Participants
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Sex: Female, Male
Female
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12 Participants
n=5 Participants
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Sex: Female, Male
Male
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0 Participants
n=5 Participants
|
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Race (NIH/OMB)
American Indian or Alaska Native
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0 Participants
n=5 Participants
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Race (NIH/OMB)
Asian
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2 Participants
n=5 Participants
|
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Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
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0 Participants
n=5 Participants
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Race (NIH/OMB)
Black or African American
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0 Participants
n=5 Participants
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Race (NIH/OMB)
White
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10 Participants
n=5 Participants
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Race (NIH/OMB)
More than one race
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0 Participants
n=5 Participants
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Race (NIH/OMB)
Unknown or Not Reported
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0 Participants
n=5 Participants
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Ethnicity (NIH/OMB)
Hispanic or Latino
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0 Participants
n=5 Participants
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Ethnicity (NIH/OMB)
Not Hispanic or Latino
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12 Participants
n=5 Participants
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Ethnicity (NIH/OMB)
Unknown or Not Reported
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0 Participants
n=5 Participants
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Region of Enrollment
United States
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12 participants
n=5 Participants
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PRIMARY outcome
Timeframe: biweekly during the MAD and every five weeks during the OLEPopulation: Subjects that had the same adverse event more than once are counted only one time using the closest relationship to study medication.
Outcome measures
| Measure |
4-week Multiple Ascending Dose (MAD)
n=12 Participants
Twelve girls with MECP2 mutations participated in the 4-week multiple ascending dose (MAD) period of open-label treatment with IGF-1 (mecasermin). The MAD focused on obtaining PK data, determining cerebrospinal fluid (CSF) penetration, and evaluating safety and tolerability of IGF-1.
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20-week Open Label Extension (OLE)
n=10 Participants
10 subjects that previously participated in the MAD went on to complete the OLE and were monitoring for safety of prolonged treatment (20 weeks).
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Adverse Events
Possibly related adverse events
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2 Adverse events
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17 Adverse events
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Adverse Events
Unrelated adverse events
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4 Adverse events
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4 Adverse events
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Adverse Events
Probably related adverse events
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2 Adverse events
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9 Adverse events
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PRIMARY outcome
Timeframe: 60 minutes pre-dose and 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 8.0, and 12.0 hours post-dose on days 1, 8, 15 and 29.Outcome measures
| Measure |
4-week Multiple Ascending Dose (MAD)
n=12 Participants
Twelve girls with MECP2 mutations participated in the 4-week multiple ascending dose (MAD) period of open-label treatment with IGF-1 (mecasermin). The MAD focused on obtaining PK data, determining cerebrospinal fluid (CSF) penetration, and evaluating safety and tolerability of IGF-1.
|
20-week Open Label Extension (OLE)
10 subjects that previously participated in the MAD went on to complete the OLE and were monitoring for safety of prolonged treatment (20 weeks).
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Pharmacokinetic (PK) Profile - Areas Under the Curve (AUCt)
Day 1: 40 mcg/kg dose
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2050.0 ng.h/mL
Standard Error 235.2
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—
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Pharmacokinetic (PK) Profile - Areas Under the Curve (AUCt)
Day 29: 120 mcg/kg dose
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3348.9 ng.h/mL
Standard Error 261.9
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—
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SECONDARY outcome
Timeframe: pre-MAD (baseline) to post-OLE (after 20 weeks of IGF-1 treatment)Population: Two subjects enrolled in the MAD did not continue participation in the OLE and one subject was excluded from the analysis because, upon further medical record review, she did not meet diagnostic criteria for Rett syndrome.
Apnea indices were compared from pre-MAD (prior to initiating treatment) to post-OLE (after 20 weeks of IGF-1 therapy). A negative value indicates a reduction in apnea index; representing an improved outcome. Apnea Index is defined as the number of apneas (≥ 10 seconds in length) occuring within one hour. The Apnea Index is calculated by dividing the number of qualifying apneic events by the number of hours in which they occurred. An apnea index greater than or equal to 5 is considered clinically significant by the American Academy of Sleep Medicine (AASM).
Outcome measures
| Measure |
4-week Multiple Ascending Dose (MAD)
n=9 Participants
Twelve girls with MECP2 mutations participated in the 4-week multiple ascending dose (MAD) period of open-label treatment with IGF-1 (mecasermin). The MAD focused on obtaining PK data, determining cerebrospinal fluid (CSF) penetration, and evaluating safety and tolerability of IGF-1.
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20-week Open Label Extension (OLE)
10 subjects that previously participated in the MAD went on to complete the OLE and were monitoring for safety of prolonged treatment (20 weeks).
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|---|---|---|
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Change From Pre-MAD Apnea Index at Post-OLE
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-7.12 apneas per hour
Standard Error 4.58
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—
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SECONDARY outcome
Timeframe: Pre-OLE (visit 1) and post-OLE (after 20 weeks of IGF-1 therapy)Population: The ADAMS was not completed during the MAD.
The Anxiety Depression and Mood Scale (ADAMS) is completed by the parent/caregiver and consists of 29 items which are scored on a 4-point rating scale that combines frequency and severity ratings. The Social Avoidance subscale \[0 = best; 20 = worst\] of the ADAMS is reported as a secondary outcome measure. A negative value indicates a decrease in the Social Avoidance subscale; which represents an improved outcome.
Outcome measures
| Measure |
4-week Multiple Ascending Dose (MAD)
n=10 Participants
Twelve girls with MECP2 mutations participated in the 4-week multiple ascending dose (MAD) period of open-label treatment with IGF-1 (mecasermin). The MAD focused on obtaining PK data, determining cerebrospinal fluid (CSF) penetration, and evaluating safety and tolerability of IGF-1.
|
20-week Open Label Extension (OLE)
10 subjects that previously participated in the MAD went on to complete the OLE and were monitoring for safety of prolonged treatment (20 weeks).
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|---|---|---|
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Change in Social Avoidance Subscale Scores on the ADAMS From Pre-OLE to Post-OLE
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-1.44 units on a scale
Standard Error 0.84
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—
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Adverse Events
Open-label IGF-1 Treatment
Serious events: 1 serious events
Other events: 12 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Open-label IGF-1 Treatment
n=12 participants at risk
Twelve girls with MECP2 mutations participated in the 4-week multiple ascending dose (MAD) period of open-label treatment with IGF-1 (mecasermin). The MAD focused on obtaining PK data, determining cerebrospinal fluid (CSF) penetration, evaluating safety and tolerability, and estimating feasibility of automated cardiorespiratory measures as biomarkers. Mecasermin was escalated over a 4-week period, beginning with twice daily injections of 40 mcg/kg the first week, 80 mcg/kg the second week, and 120 mcg/kg during the third and fourth weeks. CSF samples were obtained prior to initiating treatment and after completing the fourth week.
10 of these subjects went on to complete the open label extension (OLE). The OLE was designed to obtain additional information on safety, tolerability, and cardiorespiratory measures after 20-weeks of treatment, as well as preliminary data on neurologic and behavioral parameters. During the 20-week OLE subjects were evaluated every 5 weeks.
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Respiratory, thoracic and mediastinal disorders
Respiratory distress
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8.3%
1/12 • Number of events 1 • During the MAD and OLE (approximately 1 year, 4 months)
AEs were assessed by guidelines published by the National Institutes of Health, National Cancer Institute, Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 Published: May 28, 2009 (v4.03: June 14, 2010)
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Other adverse events
| Measure |
Open-label IGF-1 Treatment
n=12 participants at risk
Twelve girls with MECP2 mutations participated in the 4-week multiple ascending dose (MAD) period of open-label treatment with IGF-1 (mecasermin). The MAD focused on obtaining PK data, determining cerebrospinal fluid (CSF) penetration, evaluating safety and tolerability, and estimating feasibility of automated cardiorespiratory measures as biomarkers. Mecasermin was escalated over a 4-week period, beginning with twice daily injections of 40 mcg/kg the first week, 80 mcg/kg the second week, and 120 mcg/kg during the third and fourth weeks. CSF samples were obtained prior to initiating treatment and after completing the fourth week.
10 of these subjects went on to complete the open label extension (OLE). The OLE was designed to obtain additional information on safety, tolerability, and cardiorespiratory measures after 20-weeks of treatment, as well as preliminary data on neurologic and behavioral parameters. During the 20-week OLE subjects were evaluated every 5 weeks.
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|---|---|
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Endocrine disorders
Polydipsia
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50.0%
6/12 • Number of events 6 • During the MAD and OLE (approximately 1 year, 4 months)
AEs were assessed by guidelines published by the National Institutes of Health, National Cancer Institute, Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 Published: May 28, 2009 (v4.03: June 14, 2010)
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Respiratory, thoracic and mediastinal disorders
Upper respiratory tract infection
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16.7%
2/12 • Number of events 2 • During the MAD and OLE (approximately 1 year, 4 months)
AEs were assessed by guidelines published by the National Institutes of Health, National Cancer Institute, Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 Published: May 28, 2009 (v4.03: June 14, 2010)
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Respiratory, thoracic and mediastinal disorders
Tonsillar Hypertrophy
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16.7%
2/12 • Number of events 2 • During the MAD and OLE (approximately 1 year, 4 months)
AEs were assessed by guidelines published by the National Institutes of Health, National Cancer Institute, Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 Published: May 28, 2009 (v4.03: June 14, 2010)
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Respiratory, thoracic and mediastinal disorders
Snoring
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41.7%
5/12 • Number of events 5 • During the MAD and OLE (approximately 1 year, 4 months)
AEs were assessed by guidelines published by the National Institutes of Health, National Cancer Institute, Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 Published: May 28, 2009 (v4.03: June 14, 2010)
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Gastrointestinal disorders
Vomiting
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16.7%
2/12 • Number of events 5 • During the MAD and OLE (approximately 1 year, 4 months)
AEs were assessed by guidelines published by the National Institutes of Health, National Cancer Institute, Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 Published: May 28, 2009 (v4.03: June 14, 2010)
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Gastrointestinal disorders
Salivary hypersecretion
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16.7%
2/12 • Number of events 2 • During the MAD and OLE (approximately 1 year, 4 months)
AEs were assessed by guidelines published by the National Institutes of Health, National Cancer Institute, Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 Published: May 28, 2009 (v4.03: June 14, 2010)
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Skin and subcutaneous tissue disorders
Nonscarring hair loss
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16.7%
2/12 • Number of events 2 • During the MAD and OLE (approximately 1 year, 4 months)
AEs were assessed by guidelines published by the National Institutes of Health, National Cancer Institute, Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 Published: May 28, 2009 (v4.03: June 14, 2010)
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Reproductive system and breast disorders
Precocious puberty
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33.3%
4/12 • Number of events 4 • During the MAD and OLE (approximately 1 year, 4 months)
AEs were assessed by guidelines published by the National Institutes of Health, National Cancer Institute, Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 Published: May 28, 2009 (v4.03: June 14, 2010)
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Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place