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Trial · Interventional

CompletedPhase 1Results postedRegistry data

Treatment of Rett Syndrome With rhIGF-1 (Mecasermin [rDNA]Injection)

NCTNCT01253317 (opens ClinicalTrials.gov in a new tab)Other id10-08-0403
Open at ClinicalTrials.govAsk about this trial

Overview

Status
Completed
Phase
Phase 1
Enrollment
12 participants (actual)
Sponsor
Boston Children's Hospital · Other
Design
Allocation not applicable · Open label (no masking)
Countries
1 country

United States

Start
Dec 2010
Primary completion
Sept 2012
Completion
Jan 2013
First posted
3 Dec 2010 (estimated)
Last update posted
22 Jun 2017
Conditions
Rett Syndrome

Timeline

1 trial · 1 completed · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
20102011201220132014
  1. Ph 1

    Treatment of Rett Syndrome With rhIGF-1 (Mecasermin [rDNA]Injection)

    NCT01253317

    Dec 2010 to Jan 2013

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

The investigators are recruiting children for a research study using a medication known as IGF-1 (mecasermin or INCRELEX) to see if it improves the health of children with Rett syndrome (RTT). To participate in the study your child must be female, between the ages of 2 to 12 and have a genetic diagnosis (MECP2 deletion or mutation) of Rett Syndrome. As you may know, there is no treatment for this illness. Currently, the standard management of Rett syndrome is supportive, which means attempting to prevent complications and treatment of symptoms. This study involves testing an investigational drug, which means that even though IGF-1 is approved by the Food and Drug Administration (FDA) for use in children, it has not been used before to treat Rett syndrome specifically. Information from this research will help determine whether the drug should be approved by the FDA in the future for the treatment of Rett Syndrome. There are five major goals to this study: 1. As one of the features of Rett Syndrome is unstable vital signs, the investigators are trying to determine if IGF-1 has any effect on normalizing your child's pulse, blood pressure and breathing pattern. 2. The safety of IGF-1 in children with Rett syndrome. The study personnel will ask you to complete a medication diary and side effect reporting form on a regular basis. They will assist you in completing this by telephone interviews. Your child will undergo 2 lumbar punctures performed at the bedside in the clinical research facility. In addition, laboratory tests will be performed throughout the study to evaluate the safety of IGF-1. These will be blood tests similar to those provided in routine clinical care. Your child will undergo regular non-invasive comprehensive physical examinations including neurological and eye examination, tonsil evaluation, electrocardiograms (ECG), measurement of height, weight and head circumference. 3. IGF-1 may improve your child's behavior, communication and speech. In order to measure this, the investigators will evaluate your child once during each month of treatment with neurodevelopmental assessments and a neurological exam. Investigators will also ask you about her behavior and day-to-day functioning through a structured parental interview and questionnaires. 4. We will examine your child's cortical function through use of electroencephalography (EEG) in conjunction with presentation of visual and auditory stimuli. EEG is a non-invasive way of recording the electrical activity of your child's brain. 5. Children with Rett Syndrome sometimes experience "flushing" in their cheeks or have exceptionally cold hands or feet and/or abnormal perspiration. The Qsensor® is a non-invasive device worn on a fabric bracelet that continually measures your child's perspiration level and body temperature. We would like to use the Qsensor® to determine whether or not IGF-1 improves these symptoms. .

Interventions

  • rhIGF-1Drug

Arms1

  • Experimental

    rhIGF-1

    Subjects will receive escalating twice-daily doses of IGF-1 over 4 weeks (40 µg/kg, 80 µg/kg, 120 µg/kg) and then continue treatment at 120 µg/kg BID for 20 weeks should they choose to enroll in the OLE.

Primary outcomes2

Outcomes the sponsor listed as primary.

  1. Adverse Events

    Time frame · biweekly during the MAD and every five weeks during the OLE

  2. Pharmacokinetic (PK) Profile - Areas Under the Curve (AUCt)

    Time frame · 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.

Secondary outcomes(2)

  1. Change From Pre-MAD Apnea Index at Post-OLE

    Time frame · pre-MAD (baseline) to post-OLE (after 20 weeks of IGF-1 treatment)

    Registry description

    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).

  2. Change in Social Avoidance Subscale Scores on the ADAMS From Pre-OLE to Post-OLE

    Time frame · Pre-OLE (visit 1) and post-OLE (after 20 weeks of IGF-1 therapy)

    Registry description

    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.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeNumber· biweekly during the MAD and every five weeks during the OLE

Adverse Events

GroupValue (Adverse events)
4-week Multiple Ascending Dose (MAD)4
20-week Open Label Extension (OLE)4
Primary outcomeMean· 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.

Pharmacokinetic (PK) Profile - Areas Under the Curve (AUCt)

GroupValue (ng.h/mL)Spread
Open-label IGF-1 Treatment2050.0235.2
Secondary and other outcome results(2)
Secondary outcomeMean· pre-MAD (baseline) to post-OLE (after 20 weeks of IGF-1 treatment)

Change From Pre-MAD Apnea Index at Post-OLE

GroupValue (apneas per hour)Spread
MAD and OLE Treatment Periods-7.124.58
Secondary outcomeMean· Pre-OLE (visit 1) and post-OLE (after 20 weeks of IGF-1 therapy)

Change in Social Avoidance Subscale Scores on the ADAMS From Pre-OLE to Post-OLE

GroupValue (units on a scale)Spread
20-week Open Label Extension (OLE)-1.440.84

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
Open-label IGF-1 TreatmentTwelve 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.–1 / 1212 / 12

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies0

Studies that cite this trial.

No study cites this trial.

Eligibility

Who could join, as posted.

Sex
Female
Age
from 2 Years up to 12 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
Inclusion Criteria: * female * with RTT (typical or variant) as defined using the internationally agreed 2010 RettSearch criteria. * genetically defined mutation or deletion of the MECP2 gene. * Girls will have the following prepubertal status: (1) Tanner stage 1 or 2 breast development; (2) Tanner stage 1 or 2 pubic hair development; (3) and younger than 12 years by bone age. * Chronological age must be 2 years or older Exclusion Criteria: * prior therapeutic use of IGF-1, growth hormone, Lupron® or sex steroids * allergy to the trial product * co-morbid or chronic illness beyond that known to be associated with Rett Syndrome: diabetes mellitus, fatty acid oxidation disorder, chromosomal aneuploidy, syndromes associated with high risk of malignancy, current or previous exposure to spinal irradiation or history of malignancy. * severe scoliosis (defined as a spinal curve of 70 degrees or more as measured on clinical and radiological examination)

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