A Phase 1/2 Randomized, Double-blind, Placebo-controlled, Multicenter, Ascending Dose, Safety and PK/PD Study of SHP655 (rADAMTS13) in Sickle Cell Disease at Baseline Health and During Acute Vaso-Occlusive Crisis

Study point of contact

Shire Contact
+1 866 842 5335
[email protected]

Locations

6 United States sites

Age

18 to 65 Years

Genotypes

HbSS

Phase

Phase 1/Phase 2

Study type

Interventional

Gender

All

Interventions

Drug

Other

Compensation

Unknown

About the study

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK),
pharmacodynamics (PD) and efficacy of SHP655 in participants with baseline health sickle cell
disease (SCD) and SCD with acute vaso-occlusive crisis (VOC).

participation requirements

Part B Only:

– The participant must have uncomplicated acute VOC (no significant organ dysfunction
[Alanine aminotransferase (ALT) >3x upper limit of normal (ULN) of local lab;
creatinine greater than (>) 2 milligram per deciliter (mg/dL); symptomatic cardiac
decompensation, new neurologic symptoms] or signs or symptoms of systemic infection,
or fever with body temperature of greater than or equal to (>=) 38.5 degree
celsius(ºC)].

– The participant requires hospitalization and parenteral narcotic treatment.

– The participant must be able to receive the first IP dose within 24 hours after first
administration of the IV narcotic dose.

– Outpatient healthcare facility treatment, if any, for the same VOC episode has
occurred no greater than 48 hours prior to screening.

Part A and B:

– 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.

participation restrictions

Part A only:

-The participant was diagnosed with acute VOC in last 21 days, at screening visit.

Part B only:

-The participant has experienced > = 6 episodes of acute VOC in last 180 days, at Screening
Visit.

Parts A and B:

– The participant has undergone blood transfusion within the last 30 days or blood
transfusion on >=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).

– The participant has a hemoglobin level <5 grams per deciliter (g/dL). - The participant has a platelet count of <100 000/cubic millimeter (mm3). - Minor infection that does not meet the following criteria: uncomplicated urinary tract infection with body temperature <38.5°C [101.3°F] and no costovertebral angle tenderness; or uncomplicated otitis media; or uncomplicated streptococcal pharyngitis. - The participant has fever with body temperature of >= 38.5ºC (101.3ºF) and one of the
following criteria:

1. The participant has positive finding (suspicious for infection) on diagnostic
tests, such as cerebral spinal fluid evaluation, radiographic evidence of
pulmonary infiltrate, or bacterial culture of normally sterile sites.

2. The participant has examination findings leading to diagnosed or strongly
suspected bone or joint infection.

3. There has been a determination by the participant’s physician that bacterial or
serious systemic viral infection is likely (example (eg), influenza,
mononucleosis).

– 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 SCD-related pain atypical of VOC, including pain associated with hepatic or splenic sequestration, cholecystitis, or pneumonia. - The participant has acute stroke, acute priapism, or severe avascular necrosis (when the presenting pain is only in the affected joint). - The participant has recently (within the past 28 days, from Screening Visit) undergone major surgery, requires hospitalization for other than VOC, 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 a received systemic steroid therapy within 48 hours prior to enrollment or there is the expectation that such therapy may be given during the study (inhaled or topical steroids are allowed). - For participants receiving chronic or long-acting opioids, a change in dose in the past 14 days or pain requiring medical attention in the past 14 days (change in opioid medications for acute pain in the past 48 hours and directly related to this VOC admission is allowed), at Screening Visit. - 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 (EOS) Visit. Note: a negative pregnancy test is required for women of childbearing potential.Women who are postmenopausal (age-related amenorrhea >=12 consecutive months or follicle-stimulating
hormone >40 milli-international units per milliliter[(mIU/mL]), or who had undergone
hysterectomy or bilateral oophorectomy are exempt from pregnancy testing.

– 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.

Locations

  • Birmingham, Alabama, United States, University of Alabama at Birmingham, 35249 [Recruiting]
  • Little Rock, Arkansas, United States, Arkansas Children's Hospital, 77202 [Recruiting]
  • New Orleans, Louisiana, United States, University Medical Center New Orleans, 70112 [Recruiting]
  • Columbus, Ohio, United States, Ohio State University Medical Center, 43210 [Recruiting]
  • Memphis, Tennessee, United States, University of Tennessee - Memphis, HSC, 38104 [Recruiting]
  • Richmond, Virginia, United States, VCU Health - Research Parent, 23298 [Recruiting]

More info

View on ClinicalTrials.gov
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