A Study of SHP655 (rADAMTS13) in Sickle Cell Disease

• Status: Recruiting
• Trial end date: 2022-11-02
• Target enrollment: 0
• Participant gender: All

Summary

SHP655 is a medicine used to treat sickle cell disease (SCD). The main aim of the study is to measure the safety and tolerability of SHP655 in SCD participants.

Study participants will receive SHP655 or placebo on Day 1. Their SCD will be treated by their doctor according to their doctor's usual clinical practice.

During the study, participants will be asked to follow-up on 13 days following SHP655 or placebo administration for safety assessment. Maximum duration of participation is expected to be about 2 months

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Shire
• Collaborator: Takeda Development Center Americas, Inc.

Criteria

Inclusion Criteria:

• Age 18 to 65 years at the time of signing the informed consent.

• An understanding, ability, and willingness to fully comply with study procedures and requirements.

• Ability to voluntarily provide written, signed, and dated (personally or via a legally authorized representative) informed consent to participate in the study.

• Male or female with a documented history of HbSS or HbSβo thalassemia (based on clinical record of genetic, electrophoresis, or high-performance liquid chromatography testing).

• Participant currently taking hydroxyurea must be on a stable dosing for 3 months at screening.

Exclusion Criteria:

• The participant was diagnosed with acute VOC in the 21 days before dosing on Day 1.

• The participant has undergone blood transfusion within the last 30 days or blood transfusion on greater than or equal to (>=) 2 occasions in the last 90 days, at Screening Visit.

• The participant has a history of acquired or congenital thrombotic thrombocytopenic purpura.

• The participant has serum creatinine level greater than (>) 1.2 milligrams per deciliter (mg/dL).

• The participant has alanine transaminase >3* upper limit of normal (based on clinical laboratory normal range), direct bilirubin level >2 mg/dL, or indirect bilirubin level >5 mg/dL at the Screening Visit.

• The participant has a hemoglobin level <5 grams per deciliter (g/dL) at the Screening Visit.

• The participant has a platelet count of <100 000/cubic millimeter (mm^3) at the Screening Visit.

• Signs or symptoms of infection requiring treatment with IV antibiotics during the Screening Period.

• The participant has fever with body temperature of >=38.5 degree Celsius (ºC) (101.3 degree Fahrenheit [ºF]) at the Screening Visit or before dosing on Day 1.

• The participant has Acute Chest Syndrome (ACS), diagnosed or strongly suspected, as evidenced by a new infiltrate on chest radiograph, and one or more of the following criteria:

1. Fever with body temperature >39°C (102.2°F)

2. Hypoxia (confirmed by arterial blood gases with partial pressure of arterial oxygen (PaO2) <70 millimeter of mercury [mmHg])

3. Chest pain

4. Suspicious findings on physical examination (tachypnea, intercostal retraction, wheezing, and/or rales)

• The participant has recently (within the past 28 days, from Screening Visit) undergone major surgery, requires hospitalization, documented serious bacterial infection requiring antibiotic treatment, or significant bleeding.

• The participant has had a recent (within the past 90 days, from Screening Visit) episode of stroke, transient ischemic attack, symptomatic pulmonary hypertension, or seizure.

• Any history of hemorrhagic stroke or bleeding diathesis.

• The participant has received any of the following protocol-restricted medicines: a) systemic steroid therapy within 48 hours before dosing, or there is the expectation that such therapy may be given during the study (inhaled or topical steroids are allowed); b) Anticoagulant or antiplatelet therapy within the past 3 weeks before dosing; c) crizanlizumab within the past 30 days before dosing; d) voxelotor within the past 14 days before dosing.

• For participants receiving chronic or long-acting opioids, a change in dose or pain requiring medical attention in the past 14 days before dosing.

• The participant has a medical or psychiatric condition that, in the opinion of the investigator, may pose a risk to the participant for participation or interfere with the conduct or results of the study.

• The participant has received or plans to receive any other investigational agent within the 4 weeks prior to the study screening visit or during the course of the study.

• There is the expectation that the participant will not be able to be followed for the duration of the study.

• The participant is pregnant or lactating or a female of childbearing potential or male unable or unwilling to comply with birth control methods or abstinence until the end of study visit.

• The participant with active use of illicit drugs (excluding marijuana) and/or alcohol dependence, as determined by the investigator.

• The participant has been administered SHP655 previously.

• Known life-threatening hypersensitivity reaction, including anaphylaxis, to the parent molecule ADAMTS-13, hamster protein, or other constituents of SHP655.

• The participant has a positive test result for hepatitis B surface antigen, or hepatitis C antibody, or human immunodeficiency virus (HIV) antigen/antibody, at the Screening Visit. However, a subject with a hepatitis C antibody and a negative hepatitis C virus ribonucleic acid (RNA) polymerase chain reaction test is not excluded.