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(S)-4,5-Dihydro-2-[2-Hydroxy-4-(3,6-Dioxaheptyloxy)Phenyl]-4-Methyl-4-Thiazolecarboxylic Acid

This article discusses the ongoing clinical trials of SP-420, a novel drug being tested for the treatment of transfusion-dependent alpha or beta thalassemia. SP-420 is being evaluated in an open-label, dose-escalation, dose-finding, and proof-of-concept trial to assess its effectiveness in removing excess iron from the body and improving the quality of life for patients with these blood disorders.

Table of Contents

Introduction to SP-420

SP-420 is a new investigational drug being studied for the treatment of transfusion-dependent thalassemia, a group of inherited blood disorders that affect the body’s ability to produce hemoglobin[1]. The active substance in SP-420 is a chemical compound with a long scientific name: (S)-4,5-dihydro-2-[2-hydroxy-4-(3,6-dioxaheptyloxy)phenyl]-4-methyl-4-thiazolecarboxylic acid. This medication is being developed by Pharmacosmos A/S and is currently in Phase II clinical trials.

How SP-420 Works

SP-420 is designed to act as an iron chelator. Iron chelators are medications that bind to excess iron in the body and help remove it. In transfusion-dependent thalassemia, patients receive regular blood transfusions, which can lead to iron overload. SP-420 aims to help remove this excess iron, potentially reducing complications associated with iron buildup in various organs[1].

Target Conditions: Alpha and Beta Thalassemia

SP-420 is being studied for two main types of thalassemia[1]:

  • Alpha-thalassemia: A condition where the body doesn’t produce enough alpha globin, a component of hemoglobin.
  • Beta-thalassemia: A condition where the body doesn’t produce enough beta globin, another component of hemoglobin.
Both conditions can lead to severe anemia, requiring regular blood transfusions for survival, hence the term “transfusion-dependent”.

Current Clinical Trial

The ongoing clinical trial for SP-420 is an open-label, dose-escalation, dose-finding, and proof-of-concept study[1]. This means:

  • Open-label: Both the researchers and participants know which treatment is being given.
  • Dose-escalation: The study starts with a low dose and gradually increases it to find the optimal dose.
  • Dose-finding: The study aims to determine the most effective and safe dose of SP-420.
  • Proof-of-concept: The study seeks to verify that SP-420 works as intended in treating thalassemia.

Dosage and Administration

SP-420 is administered orally in the form of capsules. The study is testing different dosages[1]:

  1. Initially, 28 mg/kg taken orally three times per week
  2. Potentially increasing to 56 mg/kg taken orally three times per week
  3. Possibly escalating to 84 mg/kg taken orally three times per week
The maximum daily dose being tested is 84 mg/kg, with a maximum total dose of 12,096 mg/kg over a 48-week treatment period.

Eligibility Criteria

To participate in the SP-420 clinical trial, patients must meet specific criteria[1]. Some key inclusion criteria are:

  • Age 18 years or older
  • Diagnosed with transfusion-dependent alpha- or beta-thalassemia
  • Currently on stable iron chelation therapy
  • Weight of 35 kg or more
  • Evidence of iron overload in the liver
There are also several exclusion criteria, including certain medical conditions, medications, and circumstances that would make participation unsafe or potentially interfere with the study results.

Study Objectives

The main objectives of the SP-420 clinical trial include[1]:

  1. Establishing the dose-response relationship of SP-420 over 24 weeks
  2. Assessing the efficacy of SP-420 in removing iron from the liver
  3. Evaluating the drug’s ability to remove iron from the entire body
  4. Measuring the effect of SP-420 on serum ferritin levels (a measure of iron in the blood)
  5. Assessing the safety and tolerability of different doses of SP-420

Study Endpoints

The trial will measure several outcomes, known as endpoints, to determine the effectiveness and safety of SP-420[1]:

  • Primary endpoint: Total body iron removed by SP-420 from baseline to week 24
  • Secondary endpoints: Changes in liver iron concentration, total body iron removal at different time points, changes in serum ferritin levels, and the occurrence of adverse events

Safety Considerations

As with any clinical trial, patient safety is a top priority. The study includes several measures to monitor and ensure participant safety[1]:

  • Regular monitoring of liver and kidney function
  • Cardiac assessments, including MRI and ECG
  • Monitoring for potential side effects and adverse events
  • A Data Monitoring Committee to oversee the study and make recommendations on dosing
Participants will be closely monitored throughout the trial period to ensure their safety and well-being.

Aspect Details
Drug Name SP-420 ((S)-4,5-Dihydro-2-[2-Hydroxy-4-(3,6-Dioxaheptyloxy)Phenyl]-4-Methyl-4-Thiazolecarboxylic Acid)
Trial Phase Phase II
Trial Design Open-label, dose-escalation, dose-finding, and proof-of-concept
Target Condition Transfusion-dependent alpha or beta thalassemia
Primary Objective Establish dose-response relationship of SP-420 for 24 weeks
Key Secondary Objectives Assess efficacy in clearing liver iron, total body iron removal, effects on serum ferritin
Dosing Oral administration, 3 times per week, starting at 28 mg/kg with potential increases
Trial Duration 48 weeks
Key Inclusion Criteria Age ≥18 years, transfusion-dependent thalassemia, stable iron chelation, liver iron concentration ≥5 and ≤35mg/g dw
Key Exclusion Criteria Certain thalassemia variants, significant kidney or heart issues, recent use of other investigational drugs

FAQ

  • What is SP-420 and what is it being tested for? SP-420 is a new drug being tested for the treatment of transfusion-dependent alpha or beta thalassemia. It aims to remove excess iron from the body, which is a common problem for patients who require regular blood transfusions.
  • What is the main goal of the clinical trial? The main goal of the trial is to establish the dose-response relationship of SP-420 over 24 weeks in treating patients with transfusion-dependent alpha or beta thalassemia.
  • Who can participate in this clinical trial? The trial is open to men and women aged 18 and older who have transfusion-dependent alpha or beta thalassemia, weigh at least 35 kg, and meet specific criteria related to iron overload and other health conditions.
  • How is the drug administered in the trial? SP-420 is given orally (by mouth) three times per week. The trial involves different dosage groups, starting from 28 mg/kg and potentially increasing to 84 mg/kg, depending on the recommendations of the Data Monitoring Committee.
  • What are the main outcomes being measured in this trial? The primary outcome is the total body iron removed by SP-420 from baseline to week 24. Secondary outcomes include changes in liver iron concentration, total body iron removal at different time points, and changes in serum ferritin levels.

Ongoing Clinical Trials on (S)-4,5-Dihydro-2-[2-Hydroxy-4-(3,6-Dioxaheptyloxy)Phenyl]-4-Methyl-4-Thiazolecarboxylic Acid

  • Study of SP-420 for Patients with Transfusion-Dependent Alpha or Beta Thalassemia

    Recruiting

    1 1
    Investigated drugs:
    Denmark Greece Italy Poland

Glossary

  • Thalassemia: A group of inherited blood disorders that affect the body's ability to produce hemoglobin, leading to anemia and other health problems.
  • Transfusion-dependent: A condition where a person requires regular blood transfusions to maintain adequate levels of healthy red blood cells.
  • Iron overload: A condition where excess iron builds up in the body, often as a result of frequent blood transfusions, which can lead to organ damage if left untreated.
  • Liver iron concentration (LIC): A measure of iron levels in the liver, which is used to assess the degree of iron overload in the body.
  • Serum ferritin: A blood protein that contains iron and is used as an indicator of the body's iron stores.
  • R2-MRI: A specific type of magnetic resonance imaging technique used to measure iron levels in organs, particularly the liver.
  • Dose-escalation: A process in clinical trials where the dose of a drug is gradually increased to determine the optimal dosage and assess safety.
  • Open-label trial: A type of clinical trial where both the researchers and participants know which treatment is being given.
  • Proof-of-concept: A demonstration of the feasibility or potential effectiveness of a treatment or idea.
  • Data Monitoring Committee (DMC): An independent group of experts who monitor the progress of a clinical trial and can recommend changes to protect participant safety.

References

  1. http://clinicaltrials.eu/trial/study-of-sp-420-for-patients-with-transfusion-dependent-alpha-or-beta-thalassemia/