A Phase – IIa – IIb, Open Label, Single Center Trial to Study the Safety, Tolerability and Efficacy of Memantine Teva® as Supportive Long-term Treatment in Symptomatic Sickle Cell Disease

Study point of contact

Anna H Shuman, B.sc
9726494044 ext 4044
[email protected]
Ariel Koren, Professor
9726495615 ext 5615
[email protected]

Locations

1 Israel site

Age

> 10 Years

Genotypes

HbSS

Phase

Phase 2

Study type

Interventional

Gender

All

Interventions

Drug

Compensation

Unknown

About the study

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

participation requirements

– 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.

participation restrictions

– 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

Locations

  • Afula, Israel, Emek Medical Centre, 18101 [Recruiting]
Last updated 2019-10-30 Enroll Now