Phase 2a Pilot Study of NBMI Treatment in Patients With Beta Thalassemia Major, Requiring Iron Chelation

Study Overview
=================
Brief Summary
-----------------
A pilot study to explore safety and efficacy of NBMI treatment in patients with Beta Thalassemia Major requiring iron chelation Investigational product: NBMI (N1,N3-bis(2-mercaptoethyl) isophthalamide), INN: Emeramide Indication: Beta Thalassemia Major

Detailed Description
-----------------
Patients with iron overload, not controlled with current therapy will be enrolled to the study. After initial treatment with standard chelation therapy (deferasirox), patients will receive 600 mg daily dose of emeramide (NBMI) for 28 days. After that follow up period on standard treatment with deferasirox shall follow.

Official Title
-----------------
EMERA007 - An Open Label, Active-treatment Controlled, Phase 2a Pilot Study to Explore Safety and Efficacy of NBMI Treatment in Patients With Beta Thalassemia Major, Requiring Iron Chelation

Conditions
-----------------
Beta Thalassemia Major

Intervention / Treatment
-----------------
* Drug: Emeramide


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patient has clinically confirmed documented diagnosis of Beta Thalassemia Major, according to the current clinical criteria, and are on blood transfusions. Patient has been on a stable maintaince therapy with deferasirox for at least during last 3 months. Patients current chelation therapy is considered inadequate, meaning that there is evidence from clinical monitoring that chronic iron overload is present (e.g. serum ferritin >1,000 µg/l), for at least during the last 3 months. The ferritin level has been stable with max 10% difference between max-to-low, and the iron chelator treatment dose has been unchanged during the last 3 months Patient is aged 18 years or older at screening. Female patients are only eligible for the study if they are either surgically sterile or at least 2 years postmenopausal, or have a negative result of serum hCG test at screening and if willing to use acceptable, effective methods of contraception during the trial and for three month after the end of trial participation as defined inpoint 7.7. of this the protocol. Male patients must either be surgically sterile or he and his female spouse/partner who is of childbearing potential must be willing to use highly effective methods of contraception consisting of 2 forms of birth control (1 of which must be a barrier method) starting at screening and continuing throughout the study. Patient is fluent in the local language and provides written informed consent. Exclusion Criteria: Known history or presence of clinically significant other, hematologic, endocrine, oncologic, pulmonary, immunologic, genitourinary, psychiatric, or cardiovascular disease or any other condition which, in the opinion of the Investigator, would jeopardize the safety of the subject or impact the validity of the study results. Known or suspected allergy hypersensitivity or idiosyncratic reaction to NBMI or any other drug substances with similar activity. History of drug or alcohol addiction requiring treatment. History of malabsorption within the last year or presence of clinically significant gastrointestinal disease or surgery that may affect drug bioavailability, including but not limited to cholecystectomy. Presence of hepatic or renal dysfunction. (SGOT and SGPT and bilirubin > X3 (3 fold) UNL. creatinine > 1.5mg/dl). Female patient who is pregnant (serum hCG level consistent with pregnancy diagnosis); or breastfeeding. Participation in a clinical trial that involved administration of an investigational medicinal product within 90 days prior to drug administration, or recent participation in a clinical investigation that, in the opinion of the Investigator, would jeopardize subject safety or the integrity of the study results. Have clinically significant abnormal laboratory values (e.g. liver enzymes). Have clinically significant findings from a physical examination (e.g. fever). Patient has Inflammatory disorders, liver disease such as hepatitis, malignancy or other condition that could influence ferritine levels and therefore validity of study results.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: An open label, active-treatment controlled once daily oral administration for 28 days and 28 days follow up
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental: Treatment<br>28 days treatment with NBMI 600 mg/day | Drug: Emeramide<br>* Lipophilic, membrane passing Metal chelator and anti oxidant<br>* Other names: Irminix;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events | The safety assessment is based on the number, type and severity of adverse events. The incidence of adverse events will be summarized by organ class, severity and duration. | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in serum ferritin levels | Change in serum ferritin levels measured in µg/l (V2 level compared to V4 level and V5 level compared to V2 level) | 28 days | 
| Change in iron load in the liver and heart | Change in iron load in the liver and heart as measured by magnetic resonance imaging (MRI) techniques for assessing tissue iron T* (V2 level compared to V4 level and V5 level compared to V2 level) | 28 days | 
| Percentage of NBMI-treated patients who will develop a response | Percentage of NBMI-treated patients who will develop a response to NBMI (response will be defined as lack of increase of ferritin levels ) as compared between V2 level and V4 level | 28 days |