Safety of SP-420 in the Treatment of Transfusional Iron Overload

NCT04741542 | Terminated Phase 1 FDA Drug

• 2 other identifiers: CTMS 20-0138HSC20210039H
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

This study enrolls patients with myelodysplastic syndrome (MDS) and myelofibrosis (MFS), with transfusional iron overload and treats them with the investigational iron chelator, SP-420. SP-420 may be better tolerated and safer than commercially available iron chelators. Iron chelation therapy (ICT) has been shown to improve outcomes in iron overload, but adherence is poor due to problems related to ease of administration, tolerability, and safety.

Conditions

Iron Overload

Outcome Measures

Primary Outcomes (2)

• Number of adverse events

  Count of adverse events induced by SP-420

  28 Days

• Completion at original dose

  Number of subjects that completed the study at the original starting dose of that group

  28 Days

Study Arms (4)

Group A

EXPERIMENTAL

Study subjects will receive a 14mg/kg starting dose of SP-420 three times a week

Drug: SP-420

Group B

EXPERIMENTAL

Study subjects will receive a 28mg/kg starting dose of SP-420 three times a week

Drug: SP-420

Group C

EXPERIMENTAL

Study subjects will receive a 42mg/kg starting dose of SP-420 three times a week

Drug: SP-420

Group D

EXPERIMENTAL

Study subjects will receive a 56mg/kg starting dose of SP-420 three times a week

Drug: SP-420

Interventions

SP-420 DRUG

This study aims to establish the safety of SP-420 administered orally three times per week (TIW).

Also known as: (4S)-4,5-dihydro-2-[2-hydroxy-4-[2-(2-methoxyethoxy)ethoxy]phenyl]-4-methyl-4-thiazolecarboxylic acid

Group A; Group B; Group C; Group D

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18
• Diagnosis of MDS or MF with transfusional iron overload
• Patients with MDS, will include only those with MDS Revised international prognostic scoring system (IPSS-R) risk group of intermediate, high, or very high.
• Patients with MF, will include only those with Dynamic International Prognostic Scoring System-Plus (DIPSS=Plus) risk category of intermediate-1, intermediate-2, and high risk.
• Patients with sickle cell disease and transfusional iron overload
• Not appropriate for other iron chelation therapy, per physician
• Received 10 or more units of packed red blood cells in the preceding 24 months and remains red cell transfusion dependent
• ECOG ≤ 3
• ALT ≤ 3 times the upper limit of the normal range
• Estimate glomerular filtration rate calculated using Cockroft Gault of ≥ 60 mL/min/1.73m2
• Serum ferritin ≥1000 ng/ml
• Willing to comply with all study procedures and be available for the duration of the study
• Able to take oral medication and be willing to adhere to study medication for 28 days
• Female patient must be post-menopausal (no menses for \> 12 consecutive months) or surgically sterile (i.e., bilateral oophorectomy, hysterectomy, or tubal sterilization; must agree to completely abstain for heterosexual intercourse; or, if sexually active, must agree to use 1 of the following methods for birth control from the date she signs the consent form until 30 days after final dose of the study drug.
• Progesterone implant

You may not qualify if:

• History of kidney disease including the renal Fanconi syndrome
• Proteinuria on urine dipstick greater than trace positive
• Pregnant, intending to become pregnant during the study, or breastfeeding
• Receiving another investigational drug within 30 days or 3 half-lives of the discontinued investigational agent, whichever is greater, of signing consent
• History of significant hepatic impairment, defined by Child-Pugh class C
• Active hepatitis B or C disease, evidenced by positive viral PCR
• Symptomatic heart failure
• Receiving active cytotoxic chemotherapy or radiation therapy for a second malignancy (hormonal therapy or topical therapy for squamous cell/basal cell cutaneous tumors are allowed). Treatment of the underlying hematologic malignancy with azacytidine, decitabine, venetoclax, lenalidomide, or ruxolitinib is permitted. Treatment with the supportive care agents luspatercept or erythropoietin agonists is permitted.
• Concurrent treatment with Exjade/Jadenu (deferasirox), Desferal (deferoxamine), or Ferriprox (deferiprone) are not permitted. Patients are allowed to stop these chelators and participate in this trial 14 days after discontinuation of the other chelator.

Sponsors & Collaborators

• The University of Texas Health Science Center at San Antonio: lead
• Abfero Pharmaceuticals, Inc: collaborator

Study Sites (1)

Mays Cancer Center, UT Health San Antonio

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Iron Overload

Interventions

SP-420

Condition Hierarchy (Ancestors)

Iron Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Supreet Kaur, MD

  UT Health San Antonio

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 19, 2021
• First Posted: February 5, 2021
• Study Start: March 9, 2021
• Primary Completion: January 10, 2024
• Study Completion: January 10, 2024
• Last Updated: December 27, 2024

Record last verified: 2024-12

Locations

US (1)