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

NCT ID: NCT02023424

Last Updated: 2014-02-04

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-01-31
• Study Completion Date: 2015-02-28

Brief Summary

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).

Conditions

Rett Syndrome

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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).

Group Type: EXPERIMENTAL

Glatiramer Acetate (Copaxone®)

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 15 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Sheba Medical Center

OTHER_GOV

Sponsor Role: lead

Responsible Party

Prof. Bruria Ben-Zeev MD

Head of pediatric neurology unit and Israeli Rett Cener

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Bruria Ben Zeev, prof.

Role: PRINCIPAL_INVESTIGATOR

Sheba Medical Center

Andreea Nissenkorn, Dr.

Role: PRINCIPAL_INVESTIGATOR

Sheba Medical Center

Irit Avisar, R.N M.A

Role: STUDY_DIRECTOR

Sheba Medical Center

Locations

Sheba Medical Center

Ramat Gan, , Israel

Site Status: RECRUITING

Countries

Israel

Central Contacts

BRURIA BEN ZEEV, MD

Role: CONTACT

Bruria.BenZeev@sheba.health.gov.il

+972 3 5302687

Facility Contacts

BRURIA BEN ZEEV, MD

Role: primary

Bruria.BenZeev@sheba.health.gov.il

+972 3 5302687

Irit Avisar, R.N M.A

Role: backup

irit.avisar@sheba.health.gov.il

+972544222786

Other Identifiers

SHEBA-12-9855-BBZ-CTIL

Identifier Type: -

Identifier Source: org_study_id