An Open Label, Exploratory Study to Investigate the Treatment Effect of Glatiramer Acetate on Girls Woth Rett Syndrome

An Open Label, Exploratory Study to Investigate the Treatment Effect og Glatiramer Acetate (Copaxone ®) on Girls Woth Rett Syndrome

Primary Objective: To test the hypothesis that 6 months treatment with glatiramer acetate (GA) decreases epileptiform activity in young girls with Rett syndrome.

Primary Safety Objective:To evaluate the safety and tolerability of 6 months treatment with GA in these patients.

Secondary Objectives:

1. To test the hypothesis that 6 months treatment with glatiramer acetate (GA) improves respiratory dysfunction.
2. To evaluate the effect of GA treatment on general behaviour communication, hand stereotyping, feeding, sleep and other autonomic symptoms: gastrointestinal and cardiac.
3. To assess the effect of GA treatment on bodily development.

Primary Endpoint:Improvement of epileptiform activity as recorded in a 24-hours EEG.

Primary Safety Endpoint:Frequency and severity of treatment-related AEs (including safety lab parameters).

Secondary Endpoints:

1. Improvement in the scoring of breath holds and hyperventilation, as measured with non-invasive respiratory inductance plethysmography (NoxT3 device) and parents' diaries.
2. Changes in general behaviour, communication, feeding and motor skills as assessed by the investigator (based on Kerr and Naidu validated severity scores) and recorded in parents' diary.
3. Decrease in seizure frequency as reported in parents' diary.
4. Improvement in sleep schedule as recorded in a sleep diary.
5. Change in height and weight. Population:Ten girls, 6 to 15 years old, diagnosed with Rett syndrome (RTT) Study Design:This is a single - center, exploratory, open-label, study in 10 girls diagnosed with RTT. The study will consist of four parts: Screening and baseline assessments, initial and final dose-setting period, treatment period and end-of study follow-up.

Investigational Product:Glatiramer Acetate (Copaxone® , Teva Pharmaceutical Industries Ltd.) Sample Size Consideration: The planned sample size of 10 patients was considered adequate by the investigator for this phase I exploratory proof-of-concept study. The study is not expected to show statistical significance or statistical power, only a trend for the study endpoints. Each patient will serve as her own control.

Duration of Study: Approximately 8 months per patient (including up to 2 weeks pre-treatment assessment, 6 months initial dose and treatment periods and end-of study visit).

Overall study duration: the study is expected to be completed within 12 months (dependent on rate of recruitment).

Study Overview

• Status: Unknown
• Conditions: Rett Syndrome
• Intervention / Treatment: Drug: Glatiramer Acetate (Copaxone®)

• Study Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• Israel
  • Ramat Gan, Israel
    • Recruiting
    • Sheba Medical Center
    • Contact: BRURIA BEN ZEEV, MD; Phone Number: +972 3 5302687; Email: Bruria.BenZeev@sheba.health.gov.il
    • Contact: Irit Avisar, R.N M.A; Phone Number: +972544222786; Email: irit.avisar@sheba.health.gov.il
    • Principal Investigator: Bruria Ben Zeev, MD
    • Sub-Investigator: ANDREEA NISSENKORN, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 15 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Females, age 6-15 years (inclusive).
2. Patients whose parents or legal custodians have provided written informed consent to participate in the study.
3. A diagnosis of RTT (classical or variant), defined according to the internationally agreed 2010 RetSearch criteria [4].
4. Evidence of a genetically defined pathological change in the MECP2 gene (point mutation or deletion)
5. Patients with known epileptiform activity as recorded on EEG.
6. Blood pressure and heart rate within normal limits (blood pressure: systolic 90-140 mmHg; diastolic 50-90 mmHg, heart rate 40-120 beats per minute
7. An electrocardiogram (ECG) which, according to the Investigator's judgment does not contraindicate participation in the study.
8. No clinically significant abnormalities in haematology, blood chemistry lab tests at screening.
9. Parents must be able to understand the requirements of the study and must be willing to comply with the requirements of the study

Exclusion Criteria:

1. Any medical problem or chronic illness beyond those known to be associated with Rett Syndrome which, in the investigator's judgment, contraindicates administration of the study medication.
2. Severe respiratory dysfunction (defined as tracheostomy and/or chronic oxygen therapy at least 4 hours a day and/or repeated aspiration pneumonia - at least 4 in the last year).
3. Intractable seizures that started during the last 6 months prior to beginning of the study.
4. Known hypersensitivity to glatiramer or mannitol.
5. Participation in another clinical study.
6. Parents of a patient who are unable to communicate well with the investigator and staff and comply with study procedures and follow-up
7. Parents of a patient who are unwilling to sign consent form.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Copaxone; Glatiramer Acetate (Copaxone® , Teva Pharmaceutical Industries Ltd.) 20 mg daily or in an interval determined in the Dose Setting period. Administration will be subcutaneous to various areas on the body: back of the upper arms (2 areas), front and outside of thighs (2 areas), upper buttocks/rear hips (2 areas), and stomach (the abdomen).	Drug: Glatiramer Acetate (Copaxone®); GA is a potent inducer of Th2-cells and modulates these immune cells to secrete high levels of neurotrophic factors, particularly BDNF. The induced cells cross the blood brain barrier (BBB), accumulate in the CNS and express BDNF and other regulatory substances in situ.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Improvement of epileptiform activity as recorded in a 24-hours EEG.	6 months

Secondary Outcome Measures

Outcome Measure	Time Frame
1.Improvement in the scoring of breath holds and hyperventilation, as measured with non-invasive respiratory inductance plethysmography (NoxT3 device) and parents' diaries.	8 months
2. Changes in general behaviour, communication, feeding and motor skills as assessed by the investigator (based on Kerr and Naidu validated severity scores) and recorded in parents' diary.	8 months
Decrease in seizure frequency as reported in parents' diary.	8 months
Improvement in sleep schedule as recorded in a sleep diary.	8 months
Change in height and weight	8 months

Collaborators and Investigators

• Sponsor: Sheba Medical Center
• Investigators: Principal Investigator: Bruria Ben Zeev, prof., Sheba Medical Center; Principal Investigator: Andreea Nissenkorn, Dr., Sheba Medical Center; Study Director: Irit Avisar, R.N M.A, Sheba Medical Center

Study record dates

Study Major Dates

• Study Start: January 1, 2014
• Primary Completion (Anticipated): September 1, 2014
• Study Completion (Anticipated): February 1, 2015

Study Registration Dates

• First Submitted: December 23, 2013
• First Submitted That Met QC Criteria: December 23, 2013
• First Posted (Estimate): December 30, 2013

Study Record Updates

• Last Update Posted (Estimate): February 4, 2014
• Last Update Submitted That Met QC Criteria: February 3, 2014
• Last Verified: February 1, 2014

More Information

Terms related to this study

• Keywords: BDNF; GLATIRAMER ACETATE; RETT SYNDROME; COPAXONE; Bruria Ben-Zeev
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Disease; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Mental Retardation, X-Linked; Intellectual Disability; Heredodegenerative Disorders, Nervous System; Syndrome; Rett Syndrome; Physiological Effects of Drugs; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Adjuvants, Immunologic; Glatiramer Acetate; (T,G)-A-L
• Other Study ID Numbers: SHEBA-12-9855-BBZ-CTIL