A Study of SHP655 (rADAMTS13) in Sickle Cell Disease

NCT03997760 | Completed Phase 1 Results FDA Drug

• 1 other identifier: SHP655-101
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 14

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.

Conditions

Sickle Cell Disease

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious (TEAEs)

  An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this investigational product (IP) or medicinal product. TEAEs were defined as AEs that started or worsened in severity on or after the infusion of IP. A serious TEAEs was any untoward clinical manifestation of signs, symptoms or outcomes (whether considered related to investigational product or not and at any dose) which resulted in death, was life-threatening, required inpatient hospitalization, prolongation of hospitalization, was an important medical event. TEAEs included both serious and non-serious AEs.

  From date of signing informed consent up to end of study visit (Day 28)

• Number of Participants Who Developed Positive Binding Anti-ADAMTS13 and Inhibitory Anti-ADAMTS13 Antibodies to TAK-755

  Measurement of Anti-ADAMTS13 antibodies can be used to assess whether the body's immune system has been stimulated to react to TAK-755. Binding Anti-ADAMTS13 antibodies measure antibodies that are able to bind to ADAMTS13, whether or not the antibodies have an effect on how well ADAMTS13 works. An inhibitory Anti-ADAMTS13 antibody is antibody that both binds to ADAMTS13 and able to affect how well ADAMTS13 works. Binding and Inhibitory anti-ADAMTS13 antibodies were categorized as pre-existing, treatment-induced, and treatment-boosted. Pre-existing: anti-ADAMTS13 antibodies were detected in the baseline sample prior to infusion with TAK-755. Treatment-induced: no anti-ADAMTS13 antibodies were detected in baseline sample but were detected in any sample drawn after TAK-755 infusion. Treatment-boosted: anti-ADAMTS13 antibodies were pre-existing and were detected at any time after TAK-755 infusion at titers that were at least 4 steps higher than the titers detected before TAK-755 infusion.

  From date of signing informed consent up to end of study visit (Day 28)

Secondary Outcomes (16)

• Incremental Recovery (IR) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755

  Baseline (Pre-dose), 0.25, 1, 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose

• Observed Maximum Concentration (Cmax) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755

  Baseline (Pre-dose), 0.25, 1, 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose

• Time to Reach Cmax (Tmax) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755

  Baseline (Pre-dose), 0.25, 1, 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose

• Terminal Half-Life (t1/2) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755

  Baseline (Pre-dose), 0.25, 1, 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose

• Mean Residence Time From Zero to Infinite (MRT0-Inf) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755

  Baseline (Pre-dose), 0.25, 1, 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose

Study Arms (2)

TAK-755

EXPERIMENTAL

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.

Drug: TAK-755

Placebo

PLACEBO COMPARATOR

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.

Other: Placebo

Interventions

TAK-755 DRUG

Participants will receive TAK-755 as a single IV infusion at one of the 3 dose levels of 40 IU/kg, 80 IU/kg, or 160 IU/kg.

Also known as: recombinant ADAMTS13, BAX 930, SHP655

TAK-755

Placebo OTHER

Participants 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.

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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:
• Fever with body temperature \>39°C (102.2°F)
• Hypoxia (confirmed by arterial blood gases with partial pressure of arterial oxygen (PaO2) \<70 millimeter of mercury \[mmHg\])
• Chest pain
• 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.

Sponsors & Collaborators

• Shire: lead
• Takeda Development Center Americas, Inc.: collaborator

Study Sites (14)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

Arkansas Children's Hospital

Little Rock, Arkansas, 77202, United States

Location

University of Colorado Sickle Cell Treatment and Research Center

Aurora, Colorado, 80045, United States

Location

Sickle Cell Center

Denver, Colorado, 80262, United States

Location

University of Illinois

Chicago, Illinois, 60612-4325, United States

Location

Ochsner Health System

New Orleans, Louisiana, 70121, United States

Location

Johns Hopkins University School Of Medicine

Baltimore, Maryland, 21218, United States

Location

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

Location

Duke University Medical Center

Durham, North Carolina, 27705, United States

Location

East Carolina University

Greenville, North Carolina, 27858, United States

Location

Ohio State University Medical Center

Columbus, Ohio, 43210, United States

Location

Medical University of South Carolina (MUSC)

Charleston, South Carolina, 29425, United States

Location

University of Tennessee -- Memphis

Memphis, Tennessee, 38163-2116, United States

Location

VCU Health - Research Parent

Richmond, Virginia, 23298, United States

Location

Related Links

• To obtain more information on the study, click here/on this link

MeSH Terms

Conditions

Anemia, Sickle Cell

Interventions

ADAMTS13 protein, human

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

• Title: Study Director
• Organization: Shire

ClinicalTransparency@shire.com

+1 866 842 5335

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 14, 2019
• First Posted: June 25, 2019
• Study Start: October 21, 2019
• Primary Completion: October 26, 2022
• Study Completion: October 26, 2022
• Last Updated: April 23, 2024
• Results First Posted: April 23, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.

Locations

US (14)