Treatment of Rett Syndrome With Recombinant Human IGF-1

NCT01777542 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: IRB-P00005610
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Investigators are recruiting children for a clinical trial using the medication recombinant human IGF-1 (a.k.a. mecasermin or INCRELEX) to see if it improves the health of children with Rett syndrome (RTT). While IGF-1 is approved by the Food \& Drug Administration (FDA) for certain use in children, it is considered an investigational drug in this trial because it has not previously been used to treat RTT. Information from this study will help determine if IGF-1 effectively treats RTT but will not necessarily lead to FDA approval of IGF-1 as a treatment for RTT.

Conditions

Rett Syndrome

Keywords

Rett syndrome; RTT; IGF-1; autism spectrum disorder

Outcome Measures

Primary Outcomes (10)

• Rett Syndrome Behavior Questionnaire (RSBQ) - Fear/Anxiety Subscale

  The RSBQ is an informant/parent-completed measure of abnormal behaviors typically observed in individuals with RTT, which is completed by a parent/caregiver/LAR. Each item, grouped into eight domains/factors: General mood, Breathing problems, Body rocking and expressionless face, Hand behaviors, Repetitive face movements, Night-time behaviors, Fear/anxiety and Walking/standing), is scored on a Likert scale of 0-2, according to how well the item describes the individual's behavior. A score of "0" indicates the described item is "not true," a score of "1" indicates the described item is "somewhat or sometimes true," and a score of "2" indicates the described item is "very true or often true." The total sum of items in each subscale is reported. For the fear/anxiety subscale, the sum total could be between 0-8. The higher the sum total score, the greater the frequency of fear/anxiety behaviors.

  Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends

• Anxiety, Depression, and Mood Scale (ADAMS) - Social Avoidance Subscale

  The ADAMS is completed by the parent/caregiver/LAR and consists of 29 items which are scored on a 4-point rating scale that combines frequency and severity ratings. The instructions ask the rater to describe the individual's behavior over the last six months on the following scale: "0" if the behavior has not occurred, "1" if the behavior occurs occasionally or is a mild problem, "2" if the behavior occurs quite often or is moderate problem, or "3" if the behavior occurs a lot or is a severe problem. The Social Avoidance subscale of the ADAMS will be used as a primary outcome measure for this trial. The range for this subscale is 0-21. The higher the subscale score, the more problematic the behavior.

  Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends

• Clinical Global Impression - Severity (CGI-S)

  This scale is used to judge the severity of the subject's disease prior to entry into the study. The clinician will rate the severity of behavioral symptoms at baseline on a 7-point scale from not impaired to the most impaired. The scores that correspond to each possible grouping are as follows: 1=Normal, not at all impaired; 2=Borderline impaired; 3=Mildly impaired; 4=Moderately impaired; 5=Markedly impaired; 6=Severely impaired; 7=The most impaired. The possible range for reported scores is 1-7.

  Every 10 weeks during each of the two 20-week treatment periods

• Clinical Global Impression - Improvement (CGI-I)

  Each time the patient was seen after the study intervention was initiated, the clinician compared the patient's overall clinical condition to the CGI-S score obtained at the baseline (visit 1) visit. Based on information collected, the clinician determined if any improvement occurred on the following 7-point scale: 1=Very much improved since the initiation of treatment; 2=Much improved; 3=Minimally improved; 4=No change from baseline (the initiation of treatment); 5=Minimally worse; 6=Much worse; 7=Very much worse since the initiation of treatment. The possible range for reported scores is 1-7.

  Every 10 weeks during each of the two 20-week treatment periods

• Parental Global Impression - Severity (PGI-S)

  The PGI-S is the parent version of the CGI-S. Parents/caregivers/LAR are asked to rate the severity of their child's symptoms at baseline on a 7-point scale from not at all impaired to the most impaired. The parents/caregivers/LAR will complete the PGI-S at each study visit. The scores that correspond to each possible grouping are as follows: 1=Normal, not at all impaired; 2=Borderline impaired; 3=Mildly impaired; 4=Moderately impaired; 5=Markedly impaired; 6=Severely impaired; 7=The most impaired. The possible range for reported scores is 1-7.

  Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends

• Parental Global Impression - Improvement (PGI-I)

  As part of each visit after the study intervention was initiated, the parent/caregiver was asked to compare the patient's overall clinical condition to the score obtained at the baseline (visit 1) visit. Based on information collected, the clinician determined if any improvement occurred on the following 7-point scale: 1=Very much improved since the initiation of treatment; 2=Much improved; 3=Minimally improved; 4=No change from baseline (the initiation of treatment); 5=Minimally worse; 6=Much worse; 7=Very much worse since the initiation of treatment. The possible range for reported scores is 1-7.

  Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends

• Parent Targeted Visual Analog Scale (PTSVAS) - Scale 1

  The parent or caretaker identifies the three most troublesome, RTT-specific, "target" symptoms, such as inattention or breath-holding. This allows the problems that are of concern to parents and the family to be targeted in the trial. In this study the caregiver will choose three target symptoms at baseline and then rate changes in severity of each target symptom on a visual analog scale (VAS). The VAS is a 10 cm line, where a target symptom is anchored on one end with the description "the best it has ever been" and on the other with the description "the worst it has ever been." The parent was asked to marked on the line where they felt their child's symptoms currently fit best. This mark was measured as recorded as a numeric value from 0.00-10.00 cm. The higher the value, the worse the symptom.

  Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends

• Parent Targeted Visual Analog Scale (PTSVAS) - Scale 2

  The parent or caretaker identifies the three most troublesome, RTT-specific, "target" symptoms, such as inattention or breath-holding. This allows the problems that are of concern to parents and the family to be targeted in the trial. In this study the caregiver will choose three target symptoms at baseline and then rate changes in severity of each target symptom on a visual analog scale (VAS). The VAS is a 10 cm line, where a target symptom is anchored on one end with the description "the best it has ever been" and on the other with the description "the worst it has ever been." The parent was asked to marked on the line where they felt their child's symptoms currently fit best. This mark was measured as recorded as a numeric value from 0.00-10.00 cm. The higher the value, the worse the symptom.

  Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends

• Parent Targeted Visual Analog Scale (PTSVAS) - Scale 3

  The parent or caretaker identifies the three most troublesome, RTT-specific, "target" symptoms, such as inattention or breath-holding. This allows the problems that are of concern to parents and the family to be targeted in the trial. In this study the caregiver will choose three target symptoms at baseline and then rate changes in severity of each target symptom on a visual analog scale (VAS). The VAS is a 10 cm line, where a target symptom is anchored on one end with the description "the best it has ever been" and on the other with the description "the worst it has ever been." The parent was asked to marked on the line where they felt their child's symptoms currently fit best. This mark was measured as recorded as a numeric value from 0.00-10.00 cm. The higher the value, the worse the symptom.

  Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends

• Kerr Clinical Severity Scale

  The Kerr clinical severity scale (Kerr scale) is a quantitative measure of global disease severity. The Kerr scale is a summation of individual items related to Rett syndrome phenotypic characteristics. The items are based on the severity or degree of abnormality of each characteristic on a discrete scale (0, 1, 2) with the highest level corresponding to the most severe or most abnormal presentations. The possible range of scores is 0-48. The higher the score, the more severe the symptoms.

  At the start and end of each 20-week treatment period

Secondary Outcomes (7)

• Rett Syndrome Behavior Questionnaire (RSBQ)

  Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends

• Anxiety, Depression, and Mood Scale (ADAMS)

  Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends

• Mullen Scales of Early Learning (MSEL)

  At the start and end of each 20-week treatment period

• Vineland Adaptive Behavior Scales, Second Edition (VABS-II)

  At the start and end of each 20-week treatment period

• Communication and Symbolic Behavior Scales - Developmental Profile (CSBS-DP)

  Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends

Study Arms (2)

Treatment Period 1

ACTIVE COMPARATOR

One half of subjects will be randomly assigned to receive Recombinant Human Insulin Growth Factor 1 (rhIGF-1) , and the other half of subjects will be randomly assigned to receive placebo.

Drug: Recombinant Human Insulin Growth Factor 1 (rhIGF-1); Drug: Placebo

Treatment Period 2

PLACEBO COMPARATOR

Subjects that initially received Recombinant Human Insulin Growth Factor 1 (rhIGF-1) will now receive placebo, and subjects that initially received placebo will now receive Recombinant Human Insulin Growth Factor 1 (rhIGF-1).

Drug: Recombinant Human Insulin Growth Factor 1 (rhIGF-1); Drug: Placebo

Interventions

Recombinant Human Insulin Growth Factor 1 (rhIGF-1) DRUG

Subjects will receive twice daily subcutaneous injections of IGF-1.

Also known as: mecasermin [rDNA] injection, Increlex

Treatment Period 1; Treatment Period 2

Placebo DRUG

Subjects will receive twice daily subcutaneous injections of a saline solution (placebo).

Also known as: saline

Treatment Period 1; Treatment Period 2

Eligibility Criteria

• Age: 2 Years - 10 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Diagnosis of "classic" (or "typical") Rett Syndrome
• Genetic documentation of MECP2 mutation
• Subject must be post-regression (Hagberg Stage 2)
• Subject and caregiver's primary language must be English
• Subject must reside in North America (US and Canada)
• Caregiver must have internet access and be able to complete questionnaires online and communicate via email
• Subject is stable on current medications for at least 4 weeks
• Subject's regimen of non-pharmacological interventions (physical therapy, speech therapy, etc.) is stable for at least 90 days

You may not qualify if:

• Severe scoliosis (curvature \>40 degrees)
• Bone-age greater than 11 years
• Cardiomegaly (enlarged heart)
• Tanner stage 2 or higher breast development
• Allergy to IGF-1
• Prior use of IGF-1, growth hormone, or sex steroids

Sponsors & Collaborators

• Boston Children's Hospital: lead
• International Rett Syndrome Foundation: collaborator

Study Sites (1)

Boston Children's Hospital

Boston, Massachusetts, 02215, United States

Location

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MeSH Terms

Conditions

Rett Syndrome; Autism Spectrum Disorder

Interventions

mecasermin; DNA, Ribosomal; Injections; Sodium Chloride

Condition Hierarchy (Ancestors)

X-Linked Intellectual Disability; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Heredodegenerative Disorders, Nervous System; Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

DNA; Nucleic Acids; Nucleic Acids, Nucleotides, and Nucleosides; Drug Administration Routes; Drug Therapy; Therapeutics; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Results Point of Contact

• Title: Dr. Mustafa Sahin, Director of Translational Neuroscience Center
• Organization: Boston Children's Hospital

ResearchTNC@childrens.harvard.edu

617-919-6258

Study Officials

• Mustafa Sahin, MD, PhD

  Boston Children's Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Neurology

Study Record Dates

• First Submitted: January 23, 2013
• First Posted: January 29, 2013
• Study Start: January 1, 2013
• Primary Completion: July 1, 2016
• Study Completion: November 1, 2016
• Last Updated: March 26, 2018
• Results First Posted: March 26, 2018

Record last verified: 2018-03

Locations

US (1)