Extension Study of AG-348 in Adult Participants With Pyruvate Kinase Deficiency Previously Enrolled in AG-348-006 or AG348-C-007

Study at a glance

From the registry record, last updated by the sponsor on 18 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title

An Open-Label, Multicenter, Extension Study of AG-348 in Adult Subjects With Pyruvate Kinase Deficiency Previously Enrolled in AG-348 Studies

ClinicalTrials.gov ID

NCT03853798

Acronym / sponsor ID

AG348-C-011

Conditions

Pyruvate Kinase Deficiency

Phase

Phase 3

Study type

Interventional

Recruitment status

Completed

Enrolment

90 participants (actual)

Lead sponsor

Agios Pharmaceuticals, Inc.Industry (pharma, biotech, devices)

Study start

21 Mar 2019 (actual)

Primary completion

3 Jul 2024 (actual)

Study completion

3 Jul 2024 (actual)

First posted

26 Feb 2019 (actual)

Results

Posted 18 Nov 2025

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose

Treatment

Allocation

Non-randomised

Intervention model

Parallel groups

Masking

None (open label)

Number of arms

3

Who may qualify

Ages

18 years and older

Sex

All

Healthy volunteers

Not accepted

Age groups

Adult, Older adult

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Primary outcome

1. All Cohorts: Number of Participants With at Least One Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Related TEAEs and TEAEs With Severity Greater Than or Equal to Grade 3

   Time frame: Up to 197 weeks

   A clinical adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the study drug. TEAEs are AEs with an initial onset date during the on-treatment period or worsening from baseline and include both serious and non-serious TEAEs. Severity of AEs was evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE; Version 4.03): grade 1: mild; grade 2: moderate; grade 3: severe or medically significant but not immediately life-threatening; grade 4: life threatening or disabling; grade 5: death related to AE.

2. All Cohorts: Number of Participants With TEAEs Leading to Dose Reduction, Treatment Interruption and Treatment Discontinuation

   Time frame: Up to 197 weeks

   A clinical AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the study drug. TEAEs are AEs with an initial onset date during the on-treatment period or worsening from baseline and include both serious and non-serious TEAEs. Number of participants with TEAEs leading to dose reduction, treatment interruption and treatment discontinuation are reported.

3. All Cohorts: Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters Reported as Grade Greater Than or Equal to (≥)3 TEAEs

   Time frame: Up to 197 weeks

   Clinical laboratory assessments including hematology, clinical chemistry, triglycerides, urate, coagulation, urinalysis, and liver function tests were performed in the study. Clinically significant treatment-emergent laboratory abnormalities were graded according to the NCI CTCAE; Version 4.03: grade 1: mild; grade 2: moderate; grade 3: severe or medically significant but not immediately life-threatening; grade 4: life threatening or disabling; grade 5: death related to AE. Clinical significance was determined based on the judgment of the Investigator.

4. All Cohorts: Number of Participants With Clinically Significant Abnormalities in Vital Signs Measurements and Physical Examinations Reported as TEAEs

   Time frame: Up to 197 weeks

   Vital signs and physical examinations including height, weight, body mass index (BMI), systolic blood pressure, diastolic blood pressure, pulse rate, temperature were assessed. Number of participants who experienced clinically significant abnormalities in vital signs and physical examinations as TEAEs were reported. Clinical significance was determined based on the judgment of the Investigator.

5. All Cohorts: Number of Participants With Clinically Significant Abnormalities in Bone Mineral Density (BMD)

   Time frame: Up to 192 weeks

   BMD was measured by dual-energy X-ray absorptiometry (DXA) scans during the study. Number of participants with clinically significant abnormalities were reported. Clinical significance was determined based on the judgment of the Investigator.

6. All Cohorts: Change From Baseline in Adjusted Spine T-score

   Time frame: Baseline, Week 192

   T-score of adjusted spine were assessed by DXA scans. The T-score is the number of standard deviations that bone density is above or below the average. A score of ≥ -1 indicates normal bone density; score between < -1 and > -2.5 indicates a sign of osteopenia (bone density below normal), and score of ≤ -2.5 indicates a sign of osteoporosis.

7. All Cohorts: Change From Baseline in Adjusted Spine Z-score

   Time frame: Baseline, Week 192

   The Z-score is a statistical measure to describe whether a value was above or below the standard. A Z-score of 0 is equal to the standard. Lower numbers indicate values lower than the standard and higher numbers indicate values higher than the standard.

8. All Cohorts: Change From Baseline in Femoral Total T-score

   Time frame: Baseline, Week 192

   T-score of femoral total were assessed by DXA scans. The T-score is the number of standard deviations that bone density is above or below the average. A score of ≥ -1 indicates normal bone density; score between < -1 and > -2.5 indicates a sign of osteopenia (bone density below normal), and score of ≤ -2.5 indicates a sign of osteoporosis.

9. All Cohorts: Change From Baseline in Femoral Total Z-score

   Time frame: Baseline, Week 192

   The Z-score is a statistical measure to describe whether a value was above or below the standard. A Z-score of 0 is equal to the standard. Lower numbers indicate values lower than the standard and higher numbers indicate values higher than the standard.

10. All Cohorts: Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters Reported as TEAEs

    Time frame: Up to 197 weeks

    The following ECG parameters including RR, PR, heart rate-corrected QT interval using the Fridericia's formula (QRS), QT, and QTc were assessed during the study. Number of Participants with clinically significant abnormalities in ECG parameters as TEAEs were reported. Clinical significance was determined based on the judgment of the Investigator.

Results and safety

Loading the posted results from ClinicalTrials.gov…

Research links

• Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2025.
• Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
• Derived from this study: PubMed 38330179van Beers EJ, Al-Samkari H, Grace RF, Barcellini W, Glenthoj A, DiBacco M, Wind-Rotolo M, Xu R, Beynon V, Patel P, Porter JB, Kuo KHM. Mitapivat improves ineffective erythropoiesis and iron overload in adult patients with pyruvate kinase deficiency. Blood Adv. 2024 May 28;8(10):2433-2441. doi: 10.1182/bloodadvances.2023011743.
• Derived from this study: PubMed 31974203Rab MAE, Van Oirschot BA, Kosinski PA, Hixon J, Johnson K, Chubukov V, Dang L, Pasterkamp G, Van Straaten S, Van Solinge WW, Van Beers EJ, Kung C, Van Wijk R. AG-348 (Mitapivat), an allosteric activator of red blood cell pyruvate kinase, increases enzymatic activity, protein stability, and ATP levels over a broad range of PKLR genotypes. Haematologica. 2021 Jan 1;106(1):238-249. doi: 10.3324/haematol.2019.238865.
• Individual participant dataSharing planned: No

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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.

42 sites in 16 countries: see every site and its status.