A study of mitapivat in sickle cell disease

Phase 1

• Conditions: Sickle cell disease; MedDRA version: 21.0Level: PTClassification code 10040644Term: Sickle cell diseaseSystem Organ Class: 10010331 - Congenital, familial and genetic disorders; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2019-003438-18-NL
• Lead Sponsor: Julius Clinical

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-04-28
• Last Update Posted: 4 March 2024

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 10

Inclusion Criteria

1. Male or female with documented homozygous sickle cell anemia (HbSS) or HbS/beta(0 or +)-thalassemia).
2. Documented history of VOCs, and number of days admitted in hospital for acute sickle cell related complications during 24 months before inclusion.
3. SCD with at least one of the following conditions:
I.Had at least 1 (but no more than 10) VOC in the past 12 months prior to the first day of study treatment;
II.any sickle cell related hospital admission in the past 12 months prior to the first day of study treatment;
III.any history of sickle cell related complications (such as osteonecrosis, osteoporosis, nephropathy, retinopathy, leg ulcer, acute chest syndrome, acute hemolytic crisis);
IV.presence of any clinical biomarkers associated with increased mortality in SCD prior to the first day of study treatment (NT-proBNP >160 pg/mL, LDH/HbCO ratio >1,200, tricuspid regurgitant jet velocity =2.5 m/s).
4. Age 16 years and older, inclusive; subjects age 16 or 17 years must be documented Tanner Stage 5.
5. Hemoglobin =6.9 mmol/L (approx 11.1 g/dL) and >2.5 mmol/L (approx 4.0 g/dL).
6. For subjects on hydroxyurea: the dose must have been stable for at least 3 months prior the 1st day of study treatment.
7. Subjects must start or continue taking at least the equivalent of daily 0.7 mg oral folic acid for the duration of the study.
8. Have adequate organ function based on ALT, AST, bilirubin, creatinine, neutrophil and platelet count and INR.
9. Willing and able to give written informed consent and comply to all study procedures.
10. Patients with increased albumin to creatinine ratio are prioritized above patients with a normal albumin to creatinine ratio. Both are eligible.
11. For women of reproductive potential: have a negative serum pregnancy test at screening.
12. If fertile, agree to use double anticonception during the study plus 90 days (for males) or 28 days (for females) after the last dose of the study drug.
Are the trial subjects under 18? yes
Number of subjects for this age range: 2
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 8
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

Exclusion Criteria

1. More than 10 vaso-occlusive crises within the past 12 months.
2. Hospitalized for sickle cell crisis or other vaso-occlusive event within 14 days prior to the first day of study treatment (rescreening is allowed).
3.Have a point of sickling (PoS) =24.6 mmHg as quantified by the Oxygenscan during screening to exclude subjects with no clinical relevant detectable sickling.
4.Subjects age 16 or 17 years who are documented Tanner stage 1-4 (see Appendix II).
5. Receiving regularly scheduled (red blood cell) transfusion, defined as more than 4 transfusions in the 12 months prior 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.
6. Have a significant medical condition that confers an unacceptable risk to participation in the study, and/or that could confound interpretation of the study data (such as poorly controlled hypertension, cardiac diseases, cholelithiasis, cholecystitis, cholestatis hepatitis, iron overload that could result in cardiac/hepatic/pancreatic dysfunction, have diagnosis of other congenital or acquired blood disorder, active hepatitis B or C infection or antibodies, HIV-1 of HIV-2 antibodies, active infections, poorly controlled diabetes mellitus, history of primary malignancy (except for non-melanomatous skin cancer, curatively treated cervical or breast carcinoma in situ with no known active disease present and no treatment administered during the last 3 years, unstable extramedullary hematopoiesis that could pose a risk of imminent neurologic compromise, severe hepatic fibrosis/cirrhosis or NASH, current or recent history of psychiatric disorder that could compromise the ability of the subject to cooperate with study visits and procedures.
7. Are currently enrolled in another therapeutic clinical trial involving ongoing therapy with any investigational or marketed product or placebo. Participation in registry studies is allowed.
8. Have exposure to any investigational drug, device, or procedure within 3 months prior to the first dose of study treatment.
9. Have had any prior treatment with a pyruvate kinase activator.
10. Have a prior bone marrow or stem cell transplant.
11. Are currently pregnant or breastfeeding, or planning to become pregnant during the course of the study.
12. Have a history of major surgery within 6 months of signing informed consent. Note that procedures such as laparoscopic gallbladder surgery are not considered major in this context.
13. Are currently receiving medications that are strong inhibitors of CYP3A4 or strong inducers of CYP3A4 that have not been stopped for a duration of at least 5 days or a timeframe equivalent to 5 half-lives (whichever is longer) prior to the first dose of study treatment.
14. Are currently receiving hematopoietic stimulating agents (eg, erythropoietins, granulocyte colony stimulating factors, thrombopoietins) that have not been stopped for a duration of at least 28 days prior to the first dose of study treatment.
15. Known allergy to mitapivat or its excipients (microcrystalline cellulose, croscarmellose sodium, sodium stearyl fumarate, and mannitol) or history of acute allergic reaction to drugs characterized by acute hemolytic anemia, drug-induced liver injury, anaphylaxis, rash of erythema multiforme type or Stevens-Johnson syndrome, cholestatic hepatitis, or other serious clinical manifestations.
16. For men and women of reproductive potential: unwillingne

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified