Sickle Cell DiseasePhase 2NCT06286046
A Study of Mitapivat in Participants With Sickle Cell Disease and Nephropathy
A Phase 2 study testing Mitapivat in people with Sickle Cell Disease and Nephropathy, run by Agios Pharmaceuticals, Inc..
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. Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Sickle Cell Disease, Nephropathy
- What is being tested?
- Mitapivat
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Mar 2026to Dec 2028
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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;
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- 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.
Who cannot join
- 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;
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- 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;
About this study
Official title: A Phase 2, Open-label, Multicenter Study of Mitapivat in Subjects With Sickle Cell Disease and Nephropathy (RESIST)
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.
- Conditions
- Sickle Cell Disease, Nephropathy
- Being tested
- Mitapivat
- Keywords
- AG-348, Mitapivat
- Medical subject headings
- Anemia, Sickle Cell, Kidney Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MitapivatDrug
Also called AG-348, Mitapivat sulfate, AG-348 sulfate hydrate
Tablets
| Study group | Role | What they receive |
|---|---|---|
| Mitapivat 100 mg | Experimental | Participants will receive mitapivat 100 milligrams (mg) tablet, orally, twice daily (BID) for up to 24 months. Receives: Drug: Mitapivat |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline up to 6 months
Secondary outcomes (6)
Change From Baseline in Cystatin C and Creatinine-based Estimated Glomerular Filtration Rate (eGFRcr-cys)
Measured: Baseline up to 25 months
Change From Baseline in Albumin Creatinine Ratio (ACR)
Measured: Baseline up to 25 months
Percentage of Participants With Stable ACR
Stable ACR is defined as Month 6 ACR within 20% of baseline ACR.
Measured: Baseline up to 6 months
Annualized Rate of Emergency Room (ER) Visits
Measured: Up to 24 months
Annualized Rate of Days of Hospitalizations
Measured: Up to 24 months
Type, Frequency, Severity, and Relationship to Study Drug of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Measured: Up to 25 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Feb 2024
- Study startMar 2026 (estimated)
- Primary completionMay 2027 (estimated)
- Study completionDec 2028 (estimated)
Why it stopped: Withdrawn prior to study start per sponsor decision. No patients were enrolled.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Sickle Cell DiseaseStudies of the same condition, open and under way.
- More trials run by Agios Pharmaceuticals, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Agios Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Affairs, Study chair, Agios Pharmaceuticals, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06286046
- Sponsor's protocol ID
- AG348-C-026
- Other IDs
- 2023-510289-28-00, 2023
- Status last verified
- Mar 2026
- First submitted
- 23 Feb 2024
- Last updated
- 3 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Abbasi M, Srivastava A, Saraf SL. Management of Kidney Disease with Sickle Cell Disease. J Am Soc Nephrol. 2025 Oct 1;36(10):2041-2054. doi: 10.1681/ASN.0000000804. Epub 2025 Jun 26.
PubMed 40569673
Study at a glance
From the registry record, last updated by the sponsor on 3 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Open-label, Multicenter Study of Mitapivat in Subjects With Sickle Cell Disease and Nephropathy (RESIST)
- ClinicalTrials.gov ID
- NCT06286046
- Acronym / sponsor ID
- AG348-C-026
- Conditions
- Sickle Cell Disease, Nephropathy
- Keywords
- AG-348, Mitapivat
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Withdrawn prior to study start per sponsor decision. No patients were enrolled.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Agios Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- Mar 2026 (estimated)
- Primary completion
- May 2027 (estimated)
- Study completion
- Dec 2028 (estimated)
- First posted
- 29 Feb 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Mitapivat 100 mg | Experimental | Drug: MitapivatParticipants will receive mitapivat 100 milligrams (mg) tablet, orally, twice daily (BID) for up to 24 months. |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (10 listed)
- Age of 16 years or older (except in France where participants must be aged 18 years or older);
- 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;
- 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;
Key exclusion criteria (13 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MitapivatAlso: AG-348, Mitapivat sulfate, AG-348 sulfate hydrateTablets | Drug | Mitapivat 100 mg |
Primary outcome
Percentage of Participants With Albumin Creatinine Ratio (ACR) Response
Time frame: Baseline up to 6 months
The ACR response is defined as a decrease of 30% or more in ACR from the baseline to Month 6.
6 secondary outcomes
Change From Baseline in Cystatin C and Creatinine-based Estimated Glomerular Filtration Rate (eGFRcr-cys)
Time frame: Baseline up to 25 months
Change From Baseline in Albumin Creatinine Ratio (ACR)
Time frame: Baseline up to 25 months
Percentage of Participants With Stable ACR
Time frame: Baseline up to 6 months
Annualized Rate of Emergency Room (ER) Visits
Time frame: Up to 24 months
Annualized Rate of Days of Hospitalizations
Time frame: Up to 24 months
Type, Frequency, Severity, and Relationship to Study Drug of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: Up to 25 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Apr 2026.
- Derived from this study: PubMed 40569673Abbasi M, Srivastava A, Saraf SL. Management of Kidney Disease with Sickle Cell Disease. J Am Soc Nephrol. 2025 Oct 1;36(10):2041-2054. doi: 10.1681/ASN.0000000804. Epub 2025 Jun 26.
- Individual participant dataSharing planned: No
Related trials for Sickle Cell Disease
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HPC Offered for PRESERVE Expansion
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Study to Evaluate the Safety and Tolerability of Escalating Doses of Fostamatinib in Subjects With Stable Sickle Cell Disease
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Affairs study chair
Agios Pharmaceuticals, Inc.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Mitapivat in people with Sickle Cell Disease and Nephropathy, run by Agios Pharmaceuticals, Inc..
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 3 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With Albumin Creatinine Ratio (ACR) Response (time frame: Baseline up to 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06286046, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Apr 2026.