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

NCT01253317 | Completed Phase 1 Results DMC

• 1 other identifier: 10-08-0403
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

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. 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. 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. 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. 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. 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.

Conditions

Rett Syndrome

Keywords

Rett Syndrome; IGF-1; Increlex; Mecasermin; IGF1; MECP2; RTT

Outcome Measures

Primary Outcomes (2)

• Adverse Events

  biweekly during the MAD and every five weeks during the OLE

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

  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)

• Change From Pre-MAD Apnea Index at Post-OLE

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

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

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

Study Arms (1)

rhIGF-1

EXPERIMENTAL

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.

Drug: rhIGF-1

Interventions

rhIGF-1 DRUG

1\) Multiple ascending dose (MAD) period (4 weeks): 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 open-label extension period.

Also known as: Mecasermin (brand name Increlex)

rhIGF-1

Eligibility Criteria

• Age: 2 Years - 12 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

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

Study Sites (1)

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Related Links

• International Rett Syndrome Foundation website
• Autism Speaks website
• PNAS publication of phase 1 IGF-1 trial in RTT

MeSH Terms

Conditions

Rett Syndrome

Interventions

mecasermin

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

Results Point of Contact

• Title: Walter E. Kaufmann, MD
• Organization: Boston Children's Hospital

rettresearch@childrens.harvard.edu

617-355-5230

Study Officials

• Mustafa Sahin, MD, PhD

  Boston Children's Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor in Neurology, Harvard Medical School

Study Record Dates

• First Submitted: December 2, 2010
• First Posted: December 3, 2010
• Study Start: December 1, 2010
• Primary Completion: September 1, 2012
• Study Completion: January 1, 2013
• Last Updated: June 22, 2017
• Results First Posted: June 22, 2017

Record last verified: 2017-06

Locations

US (1)