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

Iron Overload Clinical Trial

Official title:

Phase 1, Open-Label, Dose Escalation Study to Assess the Safety of SP-420 in the Treatment of Transfusional Iron Overload

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT04741542
• Other study ID #: CTMS 20-0138
• Secondary ID: HSC20210039H
• Status: Suspended
• Phase: Phase 1
• Start date: March 9, 2021
• Est. completion date: August 2025

Study information

• Verified date: December 2023
• Source: The University of Texas Health Science Center at San Antonio
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 28
• Est. completion date: August 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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. Patients with sickle cell disease and transfusional iron overload

6. Not appropriate for other iron chelation therapy, per physician

7. Received 10 or more units of packed red blood cells in the preceding 24 months and remains red cell transfusion dependent

8. ECOG = 3

9. ALT = 3 times the upper limit of the normal range

10. Estimate glomerular filtration rate calculated using Cockroft Gault of = 60 mL/min/1.73m2

11. Serum ferritin =1000 ng/ml

12. Willing to comply with all study procedures and be available for the duration of the study

13. Able to take oral medication and be willing to adhere to study medication for 28 days

14. 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

15. 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.

Related Conditions & MeSH terms

• Iron Overload

Intervention

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

Locations

Country	Name	City	State
United States	Mays Cancer Center, UT Health San Antonio	San Antonio	Texas

Sponsors (2)

Lead Sponsor	Collaborator
The University of Texas Health Science Center at San Antonio	Abfero Pharmaceuticals, Inc

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of adverse events	Count of adverse events induced by SP-420	28 Days
Primary	Completion at original dose	Number of subjects that completed the study at the original starting dose of that group	28 Days