A Phase - IIa - IIb, Trial to Study the Safety, Tolerability and Efficacy of Memantine as a Long-term Treatment of SCD

NCT03247218 | Unknown Phase 2 DMC

• 1 other identifier: 071-17 EMC
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Symptomatic sickle cell disease (SCD) is worldwide the most frequent cause for hereditary hemolytic anemia with recurrent pain crises. Hemolysis, vaso- occlusive and pain crises are hallmarks of this disease and are causative for an important socio-economic burden worldwide, especially in Africa. Aside from allogenic stem cell transplantation, which is rarely available and very expensive, at present there is no curative treatment for patients with SCD. The current standard of care includes treatment with Hydroxyurea and symptomatic care such as transfusions, antibiotic/analgesic treatment. Recent findings allowed the investigators to come up with a novel pharmacological target for prophylactic treatment of this group of patients. The investigators showed that N-methyl D-aspartate receptors (NMDARs) are substantially up-regulated in circulating red blood cells (RBCs) of SCD patients. Ca2+ uptake via these non-selective cation channels has major impact on RBC hydration and facilitates polymerization of deoxygenated hemoglobin S variant in RBCs of patients. In vitro observations shows that inhibition of NMDARs with Memantine caused re-hydration and largely prevented hypoxia-induced sickling in RBCs. A pilot trial MemSID (NCT02615847) was conducted in August 2015-March 2017 at the Hematology Division of University Hospital Zurich. A small cohort of adult SCD patients was treated with 20 mg Memantine daily to test safety, tolerability and efficacy of this drug and to assess the effect of Memantine on hemolytic activity and RBC stability. Pilot data reveal safety and an impressive therapeutic potential of Memantine in treating SCD patients. Due to a small number of SCD patients in Switzerland, an extended trial including larger number of adult and adolescent patients will be performed at the Pediatric Hematology Unit of the Emek Medical Center in Afula, Israel

Conditions

Sickle Cell Disease

Outcome Measures

Primary Outcomes (1)

• Assessment of Incidence and severity of Memantine treatment-related Adverse Events (AE), including clinically significant abnormal laboratory values in adult and adolescent patients with symptomatic SCD.

  The following laboratory parameters will be assessed and evaluated: * Complete blood count. * Hemolytic activity (reticulocytes, indirect bilirubin and LDH). * Iron status (ferritin, serum iron, transferrin and transferrin saturation). * Fetal hemoglobin levels * Red cell volume, density, membrane stability, adherablilty, inflammatory markers and metabolic activity.

  one year

Secondary Outcomes (1)

• Assessment of Clinical Improvement during Memantine treatment compared to a pre-screening data obtained from patients clinical files in adult and adolescent patients with symptomatic SCD.

  one year

Study Arms (1)

Single group of patients

EXPERIMENTAL

In this study 40 patients with SCD will be included. Twenty patients aged 18 years or older (cohort 1) and twenty patients 10 - 17 years old (cohort 2). All the patients will receive Memantine Teva® film-coated tablets (Memantine hydrochloride) produced by Teva Pharma AG and will be provided as 5 mg, 10 mg, and 20 mg tablets packed in blister. The study drug will be taken once a day per os, during one year.

Drug: Memantine Hydrochloride

Interventions

Memantine Hydrochloride DRUG

a low-moderate affinity, uncompetitive, NMDAR antagonist

Also known as: Memantine TEVA

Single group of patients

Eligibility Criteria

• Age: 10 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Documented symptomatic sickle cell disease (HbSS or HbS/beta thalassemia)
• Age 18 years or older (cohort 1) and 10 - 17 years old (cohort 2)
• Able and willing to provide written informed consent and to comply with the study protocol procedures Willing to use two effective methods of contraception during study treatment until 6 months after stop of study treatment. Effective contraception methods are considered oral, injectable, implantative contraceptives or intrauterine contraceptive devices combined with use of condom.

You may not qualify if:

• History of transfusion during last three months before Screening
• Patients with active bacterial, viral or fungal infection requiring systemic treatment
• Patients with known infection with human immunodeficiency virus (HIV) of human T cell leukemia virus 1 (HTLV-1)
• Inadequate renal function: creatinine clearance \< 30ml/min
• Inadequate liver function: NCICTC Grade 3 liver function tests (AST, ALT \> 5x upper limit of normal (ULN))
• Patients with Chronic Active Hepatitis - HCV or HBV
• History of malignancy
• Women who are pregnant or breast feeding
• Known epileptic disease and under treatment with anticonvulsive drugs
• The receipt of any investigational product within 30 days prior to this trial

Sponsors & Collaborators

• HaEmek Medical Center, Israel: lead

Study Sites (1)

Emek Medical Centre

Afula, 18101, Israel

RECRUITING

MeSH Terms

Conditions

Anemia, Sickle Cell

Interventions

Memantine

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Amantadine; Adamantane; Bridged-Ring Compounds; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Ariel Koren, Professor

  Emek Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ariel Koren, Professor

CONTACT

9726495615; koren_a@clalit.org.il

Anna H Shuman, B.sc

CONTACT

9726494044; annami31@clalit.org.il

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Pediatric Hematology Unit

Model Details: a single center and open label study

Study Record Dates

• First Submitted: August 1, 2017
• First Posted: August 11, 2017
• Study Start: February 2, 2018
• Primary Completion: December 31, 2020
• Study Completion: December 31, 2020
• Last Updated: November 1, 2019

Record last verified: 2019-10

Data Sharing

• IPD Sharing: Will not share

Locations

IL (1)