A Study of Mitapivat in Participants With Sickle Cell Disease and Nephropathy

Sickle Cell Disease Clinical Trial

Official title:

A Phase 2, Open-label, Multicenter Study of Mitapivat in Subjects With Sickle Cell Disease and Nephropathy

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06286046
• Other study ID #: AG348-C-026
• Secondary ID: 2023-510289-28-0
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: June 2024
• Est. completion date: September 2027

Study information

• Verified date: April 2024
• Source: Agios Pharmaceuticals, Inc.
• Contact: Agios Medical Affairs
• Phone: 833-228-8474
• Email: medinfo[@]agios.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary purpose of this study is to evaluate the effect of mitapivat on albumin creatinine ratio (ACR) response in participants with sickle cell disease (SCD) and nephropathy.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 40
• Est. completion date: September 2027
• Est. primary completion date: May 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years and older

Eligibility

Key Inclusion Criteria:

• Age of 16 years or older (except in France where participants must be aged 18 years or older);
• Females must be post-menarche;
• Documented diagnosis of sickle cell disease (Homozygosity for hemoglobin S [HbSS] or Hemoglobin S/Beta 0 [HbS/ß0]-thalassemia);
• Hemoglobin concentration = 5.5 and = 10.5 grams per deciliter (g/dL) during the Screening Period. If more than one measurement is collected during the Screening Period, the average must be = 5.5 and = 10.5 g/dL;
• If taking hydroxyurea, the dose of hydroxyurea must have been stable for at least 90 days before Study Day 1 with no planned dose adjustment during the study and no sign of hematologic toxicity;
• Discontinuation of hydroxyurea requires a 90-day washout before providing informed consent/assent;
• Two urine ACR results collected during the Screening Period, both of which must be = 100 and < 2000 milligrams per gram (mg/g). One ACR result can be from an untimed urine sample collected as part of a clinic visit. The other ACR result must be from a urine sample that is the first (or second) morning void on another day;
• One ACR result > 100 mg/g within 24 weeks before providing informed consent/assent;
• If taking Angiotensin-converting enzyme (ACE) inhibitor or Angiotensin receptor blockers (ARB) therapy, must have been on stable dose for at least 90 days before providing informed consent/assent with no planned dose adjustment during the study;
• Women of childbearing potential (WOCBP) must be abstinent of sexual activities that may induce pregnancy as part of their usual lifestyle or agree to use 2 forms of contraception, one of which must be considered highly effective, from the time of providing informed consent/assent, throughout the study, and for 28 days after the last dose of study drug. The second form of contraception can include an acceptable barrier method.

Key Exclusion Criteria:

• Pregnant, breastfeeding, or parturient;
• Currently receiving regularly scheduled red RBC transfusion therapy (also termed chronic, prophylactic, or preventative transfusion); episodic transfusion in response to worsened anemia or vaso-occlusive crisis (VOC) is permitted;
• Have received an RBC transfusion within 60 days before providing informed consent/assent or during the Screening Period;
• Hospitalized within 14 days before providing informed consent/assent or during the Screening Period either for a sickle cell disease pain crisis (SCPC) or other vaso-occlusive event;
• More than 10 SCPCs in the 52 weeks before providing informed consent/assent;
• History of stroke or meeting criteria for primary stroke prophylaxis (history of 2 transcranial Doppler [TCD] measurements = 200 centimeters per second (cm/s) by nonimaging TCD or = 185 cm/s by imaging TCD) at any time;
• Renal dysfunction as defined by an eGFR < 45 milliliters per minute (mL/min)/1.73 meters per square (m^2) by the Chronic Kidney Disease Epidemiology Collaboration creatinine equation (National Kidney Foundation, 2021b) at Screening;
• History of renal disease due to another disorder (e.g., diabetes, hypertension, primary focal segmental glomerulosclerosis, autoimmune) unrelated to SCD at any time;
• Evidence of acute kidney injury (in the opinion of the Investigator) within 4 weeks before informed consent/assent or during Screening Period.
• Currently undergoing renal replacement therapy (i.e., hemodialysis, peritoneal dialysis, hemofiltration, kidney transplantation);
• History of kidney transplant at any time;
• Currently receiving treatment with a disease-modifying therapy for SCD (eg, voxelotor, crizanlizumab, L-glutamine), except for hydroxyurea. The last dose of such therapies must have been administered at least 90 days before starting study drug;
• Currently receiving treatment with hematopoietic stimulating agents; the last dose must have been administered at least 90 days before starting study drug;

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Kidney Diseases
• Nephropathy
• Sickle Cell Disease

Intervention

Drug:
• Mitapivat
Tablets

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Agios Pharmaceuticals, Inc.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Albumin Creatinine Ratio (ACR) Response	The ACR response is defined as a decrease of 30% or more in ACR from the baseline to Month 6.	Baseline up to 6 months
Secondary	Change From Baseline in Cystatin C and Creatinine-based Estimated Glomerular Filtration Rate (eGFRcr-cys)		Baseline up to 25 months
Secondary	Change From Baseline in Albumin Creatinine Ratio (ACR)		Baseline up to 25 months
Secondary	Percentage of Participants With Stable ACR	Stable ACR is defined as Month 6 ACR within 20% of baseline ACR.	Baseline up to 6 months
Secondary	Annualized Rate of Emergency Room (ER) Visits		Up to 24 months
Secondary	Annualized Rate of Days of Hospitalizations		Up to 24 months
Secondary	Type, Frequency, Severity, and Relationship to Study Drug of Adverse Events (AEs) and Serious Adverse Events (SAEs)		Up to 25 months