Senicapoc and Dehydrated Stomatocytosis

• Status: Recruiting
• Trial end date: 2023-03-01
• Target enrollment: 0
• Participant gender: All

Summary

Dehydrated stomatocytosis is a genetic disorder characterized by chronic hemolysis, variable anemia and erythrocyte dehydration. Causative mutations have been identified in either the Gardos (KCNN4) channel or the mechanosensitive channel PIEZO1. Senicapoc is a selective blocker of the Gardos channel that has been extensively studied in sickle cell disease and shown to be safe with limited side-effects. However, senicapoc did not meet the designated clinical endpoints in a pivotal phase 3 trial. The present study is an explanatory, proof-of-concept study of Senicapoc administered once daily in patients with familial dehydrated stomatocytosis caused by the autosomal dominant V282M mutation in the Gardos (KCNN4) channel.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Boston Children's Hospital; Boston Children’s Hospital
• Collaborator: Quest Diagnostics

Criteria

Inclusion Criteria:

• Members of the extended family described in 1981 by Snyder et al and Sauberman et al. and characterized molecularly by Andolfo et al. in 2015 will be eligible to participate in this study if they meet all the following criteria:

1. Have a diagnosis of dehydrated stomatocytosis with a molecularly confirmed mutation in KCNN4.

2. Are at least 21 years of age.

3. Have hematological manifestations of dehydrated stomatocytosis such as elevated MCHC, compensated or uncompensated chronic hemolysis, with reticulocytosis. For enrollment, 3/5 of the following baseline value must meet enrollment criteria:

Reference Range Enrollment criterion MCHC 32-36 mg/dL > 36 mg/dL Reticulocyte count (absolute) 0.25-0.90 x 103/µL > 0.200 x 103/µL Bilirubin, Indirect 0.2-1.2 mg/dL > 1.5 mg/dL Haptoglobin. 43-212 mg/dL < normal LDH 100-220 U/L > normal

4. Personally dated and signed informed consent detailing all the pertinent aspects of the study.

5. Willingness to adhere to study visit schedule, treatment plan, blood draws and laboratory tests and other study procedures.

Exclusion Criteria:

• Patient will be excluded from the study if they meet any of the following criteria:

• RBC transfusion in the prior 90 days.

• Recent (within the past 30 days) hospitalization for major surgical procedure, infection requiring IV treatment, or significant bleeding complications.

• Recent (within 2 weeks) diagnosis of cerebrovascular accident of transient ischemic attack.

• Hepatic dysfunction serum alanine transferase or GGT values > 3 times the upper limit of normal, total serum bilirubin values > 20 mg/dL

• Renal disease (defined as serum creatinine greater than 1.2 mg/dL, or a requirement for chronic dialysis).

• Severe symptomatic anemia defined as a Hct value < 18%.

• Any other severe acute or chronic medical condition or laboratory alteration that may increase the risks associated with participation to this study and/or administration of senicapoc, based on the clinical judgement of the principal investigator.

• Any condition that may interfere with the study subject's ability to adhere to study schedule, or comply with blood drawing requirements, such as inadequate venous access.

• Pregnancy or breastfeeding for female subjects.

• Concurrent use of illicit drugs and/or alcohol dependence, as determined by the principal investigator.