To Assess Safety of Mitapivat and Provide Proof of Concept of the Efficacy of the Drug in Patients With RBC Membranopathies or CDAII.

NCT07055243 | Recruiting Phase 2 DMC

• 1 other identifier: OZUHN-025
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective exploratory phase 2 study designed to evaluate the safety and efficacy of mitapivat in RBC membranopathies and CDAII, a rare sub type of anemia. Nine patients from Princess Margaret who are diagnosed with CDAII will be enrolled to the study. Patients will be in the trial for 57 weeks treatment weeks and a safety follow up week after 30 days from last dose. First 8 weeks will be dose escalating period followed by 48 weeks of fixed dose period. 57th week will be dose tapering week. Data collected from Princes Margaret will be incorporated to the main study conducted in EU for analysis. Overall, approximately 25 patients are expected to be enrolled: Approximately 16 patients at sites in the EU and approximately 9 patients in Canada.

Conditions

Anemia

Outcome Measures

Primary Outcomes (1)

• To evaluate safety of mitapivat

  Type, incidence, severity and relationship of mitapivat to AE and SAE

  61 weeks

Study Arms (1)

Mitapivat

EXPERIMENTAL

All patients will receive the drug Mitapivat

Drug: Mitapivat

Interventions

Mitapivat DRUG

Mitapivat will be given to adult patients with erythrocyte membranopathies

Mitapivat

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female with RBC membranopathy or congenital dyserythropoietic anemia type II (CDAII). Diagnosis must be supported genetically by a ACMG class 3 (VUS), 4 or 5 variant.
• Age ≥18 years.
• Average hemoglobin (Hb) concentration (average of at least 2 Hb measurements separated by a minimum of 7 days the during screening period) must be less than 13.0 g/dL for males and 11.0 g/dL for females. Patients with average Hb \>10.0 g/dL for males and females must meet at least one of the following additional criteria:
• Splenomegaly (length ≥12.5 cm)
• Fatigue attributed to hemolysis
• Active hemolysis as evaluated by one or more of the following: haptoglobin, bilirubin, LDH, reticulocytes
• Subjects must start or continue taking at least the equivalent of daily 0.8 mg oral folic acid for the duration of the study.
• Have adequate organ function, as defined by:
• Serum aspartate aminotransferase (AST) ≤2.5 × ULN (unless the increased AST is assessed by the Investigator as due to hemolysis and/or hepatic iron deposition) and alanine aminotransferase (ALT) ≤2.5 × ULN.
• Estimated glomerular filtration rate ≥45 mL/min/1.73 m2 by Chronic Kidney Disease Epidemiology Collaboration creatinine
• Be willing and able to give written informed consent and to comply to all study procedures for the duration of the study.
• For women of reproductive potential, have a negative urine or serum pregnancy test during the Screening Period (Day -50 to Day -1). Women of reproductive potential are defined as sexually mature women who have not undergone a hysterectomy, bilateral oophorectomy or tubal occlusion; or who have not been naturally postmenopausal (i.e. who have not menstruated at all for at least the preceding 12 months prior to signing informed consent), or has a known diagnosis of hypogonadotropic hypogonadism.
• For women of reproductive potential, be abstinent as part of their usual lifestyle, or agree to use a highly effective method of contraception. A highly effective form of contraception is defined as combined (estrogen and progestin containing) hormonal contraceptives (oral, intravaginal, or transdermal) associated with inhibition of ovulation; progestin-only hormonal contraceptives (oral, injectable, or implantable) associated with inhibition of ovulation; intrauterine device; intrauterine hormone releasing system; bilateral tube occlusion; or vasectomized partner. Women of reproductive potential using hormonal contraception as a highly effective form of contraception must also utilize an acceptable barrier method while enrolled in the study and for at least 28 days after their last dose of study drug. An acceptable barrier method includes male or female condoms with or without spermicide, and cervical cap, diaphragm, or sponge with spermicide.

You may not qualify if:

• Known history of pyruvate kinase deficiency (decreased PK activity or two pathogenic PKLR alleles). PK activity and PKLR testing is not required.
• Receiving regularly scheduled blood (RBC) transfusion therapy (also termed chronic, prophylactic or preventive transfusion), defined as more than 5 transfusion episodes in the 12-month period up to the first day of study treatment, and/or have received a transfusion within the past 3 months prior to the first day of study treatment.
• Have a significant medical condition that confers an unacceptable risk to participating in the study, and/or that could confound interpretation of the study data. Such significant medical conditions include, but are not limited to:
• Poorly controlled hypertension (defined as systolic blood pressure \>150 mm Hg or diastolic blood pressure \>90 mm Hg) refractory to medical management.
• Any history of congestive heart failure; myocardial infarction or unstable angina pectoris; hemorrhagic, embolic, or thrombotic stroke; or recent (\< 6 months prior to signing informed consent) deep venous thrombosis; or pulmonary or arterial embolism.
• Cardiac dysrhythmias judged as clinically significant by the Investigator.
• History of drug-induced cholestatic hepatitis.
• Severe iron overload as evaluated by the Investigator. This includes cardiac (eg, clinically significant impaired left ventricular ejection fraction) or hepatic (eg, fibrosis, cirrhosis) dysfunction.
• Have a diagnosis of any other congenital or acquired blood disorder or any other hemolytic process, except mild allo-immunization, as a consequence of transfusion therapy.
• g. Positive test for HBsAg or HCVAb with signs of active hepatitis B or C virus infection. Subjects with hepatitis C may be rescreened after receiving appropriate hepatitis C treatment.
• i. Positive test for HIV-1 or -2 antibodies. j. Active infection requiring the use of parenteral antimicrobial agents or Grade ≥3 in severity (per NCI CTCAE) within 2 months prior to the first dose of study treatment.
• l. History of any primary malignancy, with the exception of: curatively treated non-melanomatous skin cancer; curatively treated cervical or breast carcinoma in situ; or other primary tumor treated with curative intent, no known active disease present, and no treatment administered during the last 3 years.
• m. Unstable extramedullary hematopoiesis that could pose a risk of imminent neurologic compromise.
• n. Severe hepatic issues such as liver fibrosis (F3 or worse), significant cirrhosis or non-alcoholic fatty liver disease (NASH).
• o. Current or recent history of psychiatric disorder that, in the opinion of the Investigator, could compromise the ability of the subject to cooperate with study visits and procedures.

Sponsors & Collaborators

• University Health Network, Toronto: lead
• Agios Pharmaceuticals, Inc.: collaborator

Study Sites (1)

University Health Network (UHN)

Toronto, Ontario, M5G 2C4, Canada

RECRUITING

MeSH Terms

Conditions

Anemia

Interventions

mitapivat

Condition Hierarchy (Ancestors)

Hematologic Diseases; Hemic and Lymphatic Diseases

Central Study Contacts

Kevin Kuo, MD

CONTACT

416-340-5233; Kevin.Kuo@uhn.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 17, 2025
• First Posted: July 8, 2025
• Study Start: June 26, 2025
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2027
• Last Updated: July 8, 2025

Record last verified: 2025-07

Locations

CA (1)