Clinical trial NCT02023424: An Open Label, Exploratory Study to Investigate the Treatment Effect of Glatiramer Acetate on Girls Woth Rett Syndrome
Official title: An Open Label, Exploratory Study to Investigate the Treatment Effect og Glatiramer Acetate (Copaxone ®) on Girls Woth Rett Syndrome
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Rett Syndrome
Keywords: BDNF
GLATIRAMER ACETATE
RETT SYNDROME
COPAXONE
Bruria Ben-Zeev
Lead sponsor: Sheba Medical Center
Sponsor class: OTHER_GOV
First posted: 2013-12-30
Enrollment: 10
Sex: FEMALE
Minimum age (years): 6
Maximum age (years): 15
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).


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.

Primary outcomes:
measure: Improvement of epileptiform activity as recorded in a 24-hours EEG.
timeFrame: 6 months
Secondary outcomes:
measure: 1.Improvement in the scoring of breath holds and hyperventilation, as measured with non-invasive respiratory inductance plethysmography (NoxT3 device) and parents' diaries.
timeFrame: 8 months
measure: 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.
timeFrame: 8 months
measure: Decrease in seizure frequency as reported in parents' diary.
timeFrame: 8 months
measure: Improvement in sleep schedule as recorded in a sleep diary.
timeFrame: 8 months
measure: Change in height and weight
timeFrame: 8 months
Other outcomes:
Locations:
city: Ramat Gan
country: Israel
facility: Sheba Medical Center
Study officials:
affiliation: Sheba Medical Center
name: Bruria Ben Zeev, prof.
role: PRINCIPAL_INVESTIGATOR
affiliation: Sheba Medical Center
name: Andreea Nissenkorn, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Sheba Medical Center
name: Irit Avisar, R.N M.A
role: STUDY_DIRECTOR
References: