A Study of SHP655 (rADAMTS13) in Sickle Cell Disease (RAISE)

Shire

Status and phase: Completed; Phase 1

Conditions: Sickle Cell Disease

Treatments: Drug: TAK-755; Other: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT03997760

SHP655-101

Details and patient eligibility

About

TAK-755 (previously known as 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 TAK-755 in SCD participants.

Study participants will receive TAK-755 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.

Enrollment: 19 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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 participant with a hepatitis C antibody and a negative hepatitis C virus ribonucleic acid (RNA) polymerase chain reaction test is not excluded.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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19 participants in 2 patient groups, including a placebo group

TAK-755

Experimental group

Description:

Participants with SCD at their baseline health will receive a single intravenous (IV) infusion at one of the 3 dose levels of 40, 80 and 160 International units per kilogram (IU/kg) in a dose escalation manner.

Treatment:

Drug: TAK-755

Placebo

Placebo Comparator group

Description:

Participants with SCD at their baseline health will receive placebo matched to TAK-755 of the 3 dose levels of 40 IU/kg, 80 IU/kg, and 160 IU/kg as single IV infusion.

Treatment:

Other: Placebo