What side effects are associated with this type of intervention?

Senicapoc, a selective blocker of the Gardos channel, has been studied for its potential in treating stomatocytosis. It has been shown to be safe with limited side effects in clinical trials for sickle cell disease. Common side effects reported include mild gastrointestinal issues and fatigue. However, it did not meet the designated clinical endpoints in a pivotal phase 3 trial, indicating that while it is generally well-tolerated, its efficacy may be limited.

What prior FDA approvals exist?

There are no FDA-approved treatments specifically for stomatocytosis, including dehydrated stomatocytosis. Senicapoc, a selective blocker of the Gardos channel, has been studied for this condition but has not received FDA approval. Current treatment approaches are primarily supportive, focusing on managing symptoms and complications.

What other types of research exist?

Currently, there are no specific novel alternatives to Senicapoc mentioned for the treatment of Stomatocytosis in the provided context. Patients should consult with their healthcare provider to explore the latest research and potential new treatments targeting the Gardos channel or other related pathways.

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Potassium Channel Blocker

Senicapoc for Dehydrated Stomatocytosis

Q: What is the mechanism of action of this treatment?

Stomatocytosis is often treated with Gardos channel blockers like Senicapoc, which work by inhibiting the Gardos (KCNN4) channel responsible for potassium efflux in red blood cells. This inhibition helps to prevent the dehydration of erythrocytes, thereby reducing hemolysis and improving cell stability. For patients with Stomatocytosis, this is crucial as it directly addresses the underlying cause of their symptoms, leading to better management of anemia and overall quality of life.

Phase 1 & 2

Waitlist Available

Led By Carlo Brugnara, MD

Research Sponsored by Boston Children's Hospital

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Patients carrying KCNN4 mutations in V282M as described in 1981 by Snyder et al and Sauberman et al. and characterized molecularly by Andolfo et al. in 2015, and other patients with V282 mutations with demonstrated in-vitro sensitivity to senicapoc

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

Must not have

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

Severe symptomatic anemia defined as a Hct value < 18%

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 6 months

Awards & highlights

No Placebo-Only Group

Summary

This trial tests Senicapoc, a medication that blocks a specific channel in red blood cells, in patients with a genetic disorder causing their red blood cells to dehydrate and break down. By blocking this channel, Senicapoc aims to keep the cells hydrated and reduce anemia. Senicapoc has shown significant improvement in hemoglobin levels and reduction in dense red blood cells in previous studies.

Who is the study for?

This trial is for adults over 21 with a specific genetic blood disorder called dehydrated stomatocytosis, confirmed by certain mutations. They must be able to follow the study plan and have signs of the disease like high mean corpuscular hemoglobin concentration (MCHC) or low haptoglobin. People can't join if they've had recent strokes, transfusions, major surgeries, drug/alcohol dependence, severe anemia, are pregnant/breastfeeding or have liver/renal issues.

What is being tested?

The trial tests Senicapoc—a Gardos channel blocker—on patients with familial dehydrated stomatocytosis due to V282 mutations in KCNN4. It's a daily treatment aiming to show how well it works as proof-of-concept since previous trials in sickle cell disease didn't meet goals despite being safe.

What are the potential side effects?

Senicapoc has been found safe with limited side effects in past studies on sickle cell disease. Specific side effects aren't listed but are expected to be mild based on previous research.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have a specific KCNN4 gene mutation sensitive to senicapoc.

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I have dehydrated stomatocytosis with a confirmed KCNN4 mutation.

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I am 21 years old or older.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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My liver tests are within normal limits.

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I have severe anemia with a very low hematocrit level.

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I am not pregnant or breastfeeding.

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I have kidney issues, indicated by high creatinine or need for dialysis.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 6 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~6 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and 6 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

chronic hemolysis biomarkers

Secondary study objectives

Decrease in the frequency and intensity of pain

Improved functional health and well-being

spleen volume

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: TreatmentExperimental Treatment1 Intervention

This is a pivotal trial in members of the same family carrying the V282M nutation in the Gardos channel (KCNN4) and other patients with V282 mutations with demonstrated in-vitro sensitivity to senicapoc. These mutations lead to hyperactivation of the channel and red cell dehydration. Up to 6 patients are eligible to enroll in this study, which will assess effectiveness based on individual changes of primary endpoints over individually established baselines.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Senicapoc (synonyms: ICA-17043; 2,2-bis-(4-fluorophenyl)-2-phenylacetamide)

2021

Completed Phase 2

~10

0 / 7Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Stomatocytosis is often treated with Gardos channel blockers like Senicapoc, which work by inhibiting the Gardos (KCNN4) channel responsible for potassium efflux in red blood cells. This inhibition helps to prevent the dehydration of erythrocytes, thereby reducing hemolysis and improving cell stability. For patients with Stomatocytosis, this is crucial as it directly addresses the underlying cause of their symptoms, leading to better management of anemia and overall quality of life.

Leukocyte and bone marrow effects of a thiomorpholine quinazosin antihypertensive agent.High-dose, brief duration, multiagent chemotherapy for metastatic breast cancer.Polycythemia vera: the current status of preclinical models and therapeutic targets.