Clinical study to check the Efficacy and Safety of Mitapivat in Patients with Sickle Cell Disease

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Agios Pharmaceuticals Inc.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Decision date (initial)

2024-08-19

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Agios Pharmaceuticals, Inc.

External identifiers

EU CT number

2024-515202-84-00

EudraCT number

2021-001674-34

ClinicalTrials.gov

NCT05031780

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Efficacy, Therapy, Pharmacokinetic, Diagnosis, Dose response

"To determine the effect of mitapivat
versus placebo on: Anemia in subjects with sickle
cell disease (SCD) or Sickle cell pain crises (SCPCs) in
subjects with SCD"

Secondary objectives 1

1. "To evaluate the effect of mitapivat versus placebo on: Anemia in subjects with SCD, Markers of hemolysis, Markers of erythropoiesis, Patient-reported fatigue and Additional clinical efficacy measures related to SCPC"

Conditions and MedDRA coding

Anemia in subjects with sickle cell disease (SCD)

Study design 5 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Age ≥16 years; subjects age 16 or 17 years must be documented Tanner Stage 5 (see Appendix 3).
2. Documented diagnosis of sickle cell disease (SCD) (HbSS, HbSC [combined heterozygosity for hemoglobins S and C], HbS/β0-thalassemia, HbS/β+-thalassemia, or other sickle cell syndrome variants).
3. At least 2 sickle cell pain crises (SCPCs) (defined in Section 8.5.2.1) and no more than 10 SCPCs in the 12 months prior to providing informed assent/consent.
4. Hemoglobin ≥5.5 and ≤10.5 g/dL. Hemoglobin concentration must be based on an average of at least 2 Hb concentration measurements (separated by ≥7 days) collected during the Screening Period.
5. If taking hydroxyurea, the hydroxyurea dose must be stable for at least 90 days prior to randomization. Discontinuation of hydroxyurea requires a 90-day washout prior to informed assent/consent.
6. 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 assent/consent, 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 (see Appendix 2).
7. Written informed assent/consent (for subjects under 18 years of age, or prior to the age at which a subject is considered legally an adult per local regulations, parental permission and child assent will be obtained) must be obtained before any study-related procedures are conducted and subjects must be willing to comply with all study procedures for the duration of the study.

Exclusion criteria 10

1. Pregnant or breastfeeding.
2. Receiving regularly scheduled transfusions.
3. Hospitalized for an SCPC and/or other vaso-occlusive event within 14 days prior to providing informed assent/consent or during the Screening Period. A hospitalization is defined as an in-patient admission to a hospital that may or may not be preceded by an emergency room or out patient clinic visit. A visit to an emergency room that does not result in an in-patient admission does not meet the definition of hospitalization
4. Currently receiving treatment for SCD (eg, voxelotor, crizanlizumab, L glutamine), with the exception of hydroxyurea. The last dose of voxelotor, crizanlizumab, and L-glutamine must have been administered at least 90 days before starting study drug.
5. Currently receiving treatment with hematopoietic stimulating agents; the last dose must have been administered at least 90 days before starting study drug.
6. Received treatment on another investigational trial within 90 days prior to start of study drug or plans to participate in another investigational drug trial.
7. Taking medications that are strong inhibitors of CYP3A4/5 or strong inducers of CYP3A4 that cannot be stopped in an acceptable timeframe before starting study drug (timeframe will be discussed with your doctor).
8. Any medical, hematological, psychological, or behavioral condition(s), including alcohol use disorder, or prior or current therapy that, in the opinion of the Investigator, may confer an unacceptable risk to participating in the study.
9. Receiving herbal or dietary supplements that have not been stable in dose and preparation for ≥8 weeks prior to randomization.
10. Other protocol defined exclusion criteria may apply.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Hemoglobin (Hb) response, defined as a ≥1.0 g/dL increase in average Hb concentration from Week 24 through Week 52 compared with baseline
2. Annualized rate of SCPCs (as defined in Section 8.5.2.1)

Secondary endpoints 5

1. Average change from baseline in Hb concentration from Week 24 through Week 52
2. Average change from baseline in indirect bilirubin from Week 24 through Week 52
3. Average change from baseline in percent reticulocyte from Week 24 through Week 52
4. Average change from baseline in Patient-Reported Outcomes Measurement Information System®(PROMIS) Fatigue 13a Short Form (SF) scores from Week 24 through Week 52
5. Annualized frequency of hospitalizations for SCPC

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Agios Pharmaceuticals Inc.

Sponsor organisation

Agios Pharmaceuticals Inc.

Address

88 Sidney Street

City

Cambridge

Postcode

02139-4137

Country

United States

Scientific contact point

Organisation

Agios Pharmaceuticals Inc.

Contact name

Scientific Communications

Public contact point

Organisation

Agios Pharmaceuticals Inc.

Contact name

Scientific Communications

Third parties 16

Locations

5 EU/EEA countries · 20 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 201 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications