Clinical trial NCT03997760: A Study of SHP655 (rADAMTS13) in Sickle Cell Disease
Official title: A Phase 1 Randomized, Double-blind, Placebo-controlled, Multicenter, Ascending Dose, Safety and PK/PD Study of SHP655 (rADAMTS13) in Sickle Cell Disease at Baseline Health
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Sickle Cell Disease
Lead sponsor: Takeda
Sponsor class: INDUSTRY
Collaborators: name: Takeda Development Center Americas, Inc.
First posted: 2019-06-25
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


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

Primary outcomes:
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious (TEAEs)
timeFrame: From date of signing informed consent up to end of study visit (Day 28)
measure: Number of Participants Who Developed Positive Binding Anti-ADAMTS13 and Inhibitory Anti-ADAMTS13 Antibodies to TAK-755
timeFrame: From date of signing informed consent up to end of study visit (Day 28)
Secondary outcomes:
measure: Incremental Recovery (IR) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755
timeFrame: Baseline (Pre-dose), 0.25, 1, 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose
measure: Observed Maximum Concentration (Cmax) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755
timeFrame: Baseline (Pre-dose), 0.25, 1, 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose
measure: Time to Reach Cmax (Tmax) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755
timeFrame: Baseline (Pre-dose), 0.25, 1, 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose
measure: Terminal Half-Life (t1/2) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755
timeFrame: Baseline (Pre-dose), 0.25, 1, 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose
measure: Mean Residence Time From Zero to Infinite (MRT0-Inf) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755
timeFrame: Baseline (Pre-dose), 0.25, 1, 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose
measure: Mean Residence Time From Zero to 72 Hours Post-dose (MRT0-72) of ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755
timeFrame: Baseline (Pre-dose), 0.25, 1, 3, 8, 24, and 72 hours post-dose
measure: Area Under the Curve From Zero to Time of Last Quantifiable Concentration (AUC0-Last) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755
timeFrame: Baseline (Pre-dose), 0.25, 1, 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose
measure: Area Under the Curve Time Curve From Zero to 72 Hours Post-dose (AUC0-72) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755
timeFrame: Baseline (Pre-dose), 0.25, 1, 3, 8, 24, and 72 hours post-dose
measure: Area Under the Curve From Zero to Infinite Time (AUC0-Inf) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755
timeFrame: Baseline (Pre-dose), 0.25, 1, 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose
measure: Systemic Clearance (CL) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755
timeFrame: Baseline (Pre-dose), 0.25, 1, 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose
measure: Volume of Distribution at Steady State (Vss) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755
timeFrame: Baseline (Pre-dose), 0.25, 1, 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose
measure: Change From Baseline in Von Willebrand Factor: Antigen (VWF:Ag) at Specified Timepoints
timeFrame: Baseline (Pre-dose), 0.25, 1, 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose
measure: Change From Baseline in Von Willebrand Factor:Ristocetin Cofactor Activity (VWF:RCo) At Specified Timepoints
timeFrame: Baseline (Pre-dose), 0.25, 1, 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose
measure: Change From Baseline in Platelet Count at Specified Timepoints
timeFrame: Baseline (Pre-dose), 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose
measure: Change From Baseline in Plasma Free Hemoglobin at Specified Timepoints
timeFrame: Baseline (Pre-dose), 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose
measure: Change From Baseline in Plasma Thrombospondin Levels at Specified Timepoints
timeFrame: Baseline (Pre-dose), 3, 8, 24, 72, 120, 168, 288, and 648 hours post-dose
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Little Rock
country: United States
facility: Arkansas Children's Hospital
state: Arkansas
city: Aurora
country: United States
facility: University of Colorado Sickle Cell Treatment and Research Center
state: Colorado
city: Denver
country: United States
facility: Sickle Cell Center
state: Colorado
city: Chicago
country: United States
facility: University of Illinois
state: Illinois
city: New Orleans
country: United States
facility: Ochsner Health System
state: Louisiana
city: Baltimore
country: United States
facility: Johns Hopkins University School Of Medicine
state: Maryland
city: Charlotte
country: United States
facility: Levine Cancer Institute
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Greenville
country: United States
facility: East Carolina University
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University Medical Center
state: Ohio
city: Charleston
country: United States
facility: Medical University of South Carolina (MUSC)
state: South Carolina
city: Memphis
country: United States
facility: University of Tennessee -- Memphis
state: Tennessee
city: Richmond
country: United States
facility: VCU Health - Research Parent
state: Virginia
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: