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

• ClinicalTrials.gov Identifier: NCT04741542
• Recruitment Status: Recruiting
• First Posted: February 5, 2021
• Last Update Posted: June 25, 2021
• Sponsor: The University of Texas Health Science Center at San Antonio
• Collaborator: Abfero Pharmaceuticals, Inc
• Information provided by (Responsible Party): The University of Texas Health Science Center at San Antonio

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Iron Overload	Drug: SP-420	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 28 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase 1, Open-Label, Dose Escalation Study to Assess the Safety of Sp-420 in the Treatment of Transfusional Iron Overload in Patients With MDS(Myelodysplastic Syndrome), and MF (Myelofibrosis)
• Actual Study Start Date: March 9, 2021
• Estimated Primary Completion Date: March 2023
• Estimated Study Completion Date: March 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Group A; Study subjects will receive a 14mg/kg starting dose of SP-420 three times a week	Drug: SP-420; This study aims to establish the safety of SP-420 administered orally three times per week (TIW).; Other Name: (4S)-4,5-dihydro-2-[2-hydroxy-4-[2-(2-methoxyethoxy)ethoxy]phenyl]-4-methyl-4-thiazolecarboxylic acid
Experimental: Group B; Study subjects will receive a 28mg/kg starting dose of SP-420 three times a week	Drug: SP-420; This study aims to establish the safety of SP-420 administered orally three times per week (TIW).; Other Name: (4S)-4,5-dihydro-2-[2-hydroxy-4-[2-(2-methoxyethoxy)ethoxy]phenyl]-4-methyl-4-thiazolecarboxylic acid
Experimental: Group C; Study subjects will receive a 42mg/kg starting dose of SP-420 three times a week	Drug: SP-420; This study aims to establish the safety of SP-420 administered orally three times per week (TIW).; Other Name: (4S)-4,5-dihydro-2-[2-hydroxy-4-[2-(2-methoxyethoxy)ethoxy]phenyl]-4-methyl-4-thiazolecarboxylic acid
Experimental: Group D; Study subjects will receive a 56mg/kg starting dose of SP-420 three times a week	Drug: SP-420; This study aims to establish the safety of SP-420 administered orally three times per week (TIW).; Other Name: (4S)-4,5-dihydro-2-[2-hydroxy-4-[2-(2-methoxyethoxy)ethoxy]phenyl]-4-methyl-4-thiazolecarboxylic acid

Outcome Measures

Primary Outcome Measures :

1. Number of adverse events [ Time Frame: 28 Days ]
   Count of adverse events induced by SP-420
2. Completion at original dose [ Time Frame: 28 Days ]
   Number of subjects that completed the study at the original starting dose of that group

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Age ≥18
2. Diagnosis of MDS or MF with transfusional iron overload
3. Patients with MDS, will include only those with MDS Revised international prognostic scoring system (IPSS-R) risk group of intermediate, high, or very high.
4. 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.
5. Not appropriate for other iron chelation therapy, per physician
6. Received 10 or more units of packed red blood cells in the preceding 24 months and remains red cell transfusion dependent
7. ECOG ≤ 3
8. ALT ≤ 3 times the upper limit of the normal range
9. Estimate glomerular filtration rate calculated using Cockroft Gault of ≥ 60 mL/min/1.73m2
10. Serum ferritin ≥1000 ng/ml
11. Willing to comply with all study procedures and be available for the duration of the study
12. Able to take oral medication and be willing to adhere to study medication for 28 days

13. 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
    • Intrauterine device
    • Combination of 2 highly effective birth control methods (e.g., diaphragm/or cervical cap with spermicide plus a condom, hormonal contraception plus a barrier method, partner with vasectomy conducted >60 days before screening visit plus a hormone or barrier method
14. Male patients must agree to use 1 of the following methods for birth control from the date he signs the consent form until 30 days after final dose of the study drug: be surgically sterile by vasectomy conducted > 60 days before screening visit plus use a barrier method, or, must agree to completely abstain from heterosexual intercourse, or must agree to use a combination of 2 highly effective birth control methods (e.g., diaphragm/or cervical cap with spermicide plus a condom, hormonal contraception plus a barrier method), or have a post-menopausal partner plus barrier method.

Exclusion Criteria:

1. History of kidney disease including the renal Fanconi syndrome
2. Proteinuria on urine dipstick greater than trace positive
3. Pregnant, intending to become pregnant during the study, or breastfeeding
4. Receiving another investigational drug within 30 days or 3 half-lives of the discontinued investigational agent, whichever is greater, of signing consent
5. History of significant hepatic impairment, defined by Child-Pugh class C
6. Active hepatitis B or C disease, evidenced by positive viral PCR
7. Symptomatic heart failure
8. 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.
9. 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.

Contacts and Locations

Contacts

Contact: Epp Goodwin; 210-450-5798; goodwine@uthscsa.edu

Locations

United States, Texas

Mays Cancer Center, UT Health San Antonio; Recruiting

San Antonio, Texas, United States, 78229

Contact: Patricia Manea, RN 210-450-1821 maneap@uthscsa.edu

Principal Investigator: Elizabeth Bowhay-Carnes, MD

Sponsors and Collaborators

The University of Texas Health Science Center at San Antonio

Abfero Pharmaceuticals, Inc

Investigators

• Principal Investigator: Elizabeth Bowhay-Carnes, MD; UT Health San Antonio

More Information

• Responsible Party: The University of Texas Health Science Center at San Antonio
• ClinicalTrials.gov Identifier: NCT04741542
• Other Study ID Numbers: CTMS 20-0138; HSC20210039H ( Other Identifier: UT Health Science Center San Antonio )
• First Posted: February 5, 2021
• Last Update Posted: June 25, 2021
• Last Verified: June 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Iron Overload; Iron Metabolism Disorders; Metabolic Diseases