Clinical trial NCT06286046: A Study of Mitapivat in Participants With Sickle Cell Disease and Nephropathy
Official title: A Phase 2, Open-label, Multicenter Study of Mitapivat in Subjects With Sickle Cell Disease and Nephropathy (RESIST)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Sickle Cell Disease
Nephropathy
Keywords: AG-348
Mitapivat
Lead sponsor: Agios Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2024-02-29
Enrollment: 40
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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 \[HbS/β0\]-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;

Primary outcomes:
measure: Percentage of Participants With Albumin Creatinine Ratio (ACR) Response
timeFrame: Baseline up to 6 months
Secondary outcomes:
measure: Change From Baseline in Cystatin C and Creatinine-based Estimated Glomerular Filtration Rate (eGFRcr-cys)
timeFrame: Baseline up to 25 months
measure: Change From Baseline in Albumin Creatinine Ratio (ACR)
timeFrame: Baseline up to 25 months
measure: Percentage of Participants With Stable ACR
timeFrame: Baseline up to 6 months
measure: Annualized Rate of Emergency Room (ER) Visits
timeFrame: Up to 24 months
measure: Annualized Rate of Days of Hospitalizations
timeFrame: Up to 24 months
measure: Type, Frequency, Severity, and Relationship to Study Drug of Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Up to 25 months
Other outcomes:
Locations:
Study officials:
affiliation: Agios Pharmaceuticals, Inc.
name: Medical Affairs
role: STUDY_CHAIR
References: