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

• Status: Unknown status
• Trial end date: 2020-12-31
• Target enrollment: 0
• Participant gender: All

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

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: HaEmek Medical Center, Israel
• Treatments: Memantine

Criteria

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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