• Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: From start of study treatment up to study completion (up to Day 31) ]
  An adverse event (AE) is 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 or medicinal product. An AE can therefore be any unfavorable and unintended sign (including a clinically significant laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not causality is suspected (ICH Guidance E2A 1995). A serious adverse event (SAE) is any untoward clinical manifestation of signs, symptoms or outcomes (whether considered related to investigational product or not and at any dose) which results in death, is life-threatening, requires inpatient hospitalization, prolongation of hospitalization, is an important medical event. Number of participants with adverse events in both part A and part B will be assessed.
• Number of Participants With Incidence of Binding and Inhibitory Antibodies to SHP655 [ Time Frame: From start of study treatment up to study completion (up to Day 31) ]
  The number of participants in both part A and part B will be summarized by dose for incidence of binding and inhibitory antibodies to SHP655 and will be reported as AEs. The study completion date is defined as the date on which the last participant in the study completes the final assessments.

• Incremental Recovery (IR) of ADAMTS13 Activity and ADAMTS13 Antigen [ Time Frame: Pre-dose, 15 minutes, 1, 3, 9, 24, 72, 120, 168, 216, 288, and 744 hours post dose ]
  IR will be estimated for ADAMTS13 activity and ADAMTS13 antigen (ADAMTS13Ag) following SHP655 or placebo infusion in both part A and part B participants.
• Observed Maximum Concentration (Cmax) of ADAMTS13 Activity and ADAMTS13 Antigen [ Time Frame: Pre-dose, 15 minutes, 1, 3, 9, 24, 72, 120, 168, 216, 288, and 744 hours post dose ]
  Cmax will be estimated for ADAMTS13 activity and ADAMTS13 antigen (ADAMTS13Ag) following SHP655 or placebo infusion in participants with both part A and part B.
• Time to Reach Cmax (tmax) of ADAMTS13 Activity and ADAMTS13 Antigen [ Time Frame: Pre-dose, 15 minutes, 1, 3, 9, 24, 72, 120, 168, 216, 288, and 744 hours post dose ]
  Tmax will be estimated for ADAMTS13 activity and ADAMTS13 antigen (ADAMTS13Ag) following SHP655 or placebo infusion in participants with both part A and part B.
• Terminal Half-Life (t1/2) of ADAMTS13 Activity and ADAMTS13 Antigen [ Time Frame: Pre-dose, 15 minutes, 1, 3, 9, 24, 72, 120, 168, 216, 288, and 744 hours post dose ]
  Terminal half-life (t1/2) will be estimated for ADAMTS13 activity and ADAMTS13 antigen (ADAMTS13Ag) following SHP655 or placebo infusion in participants with both part A and part B.
• Mean Residence Time (MRT) From Zero to Infinite (MRT0-Inf) of ADAMTS13 Activity and ADAMTS13 Antigen [ Time Frame: Pre-dose, 15 minutes, 1, 3, 9, 24, 72, 120, 168, 216, 288, and 744 hours post dose ]
  MRT0-inf will be estimated for ADAMTS13 activity and ADAMTS13 antigen (ADAMTS13Ag) following SHP655 or placebo infusion in participants with both part A and part B.
• Mean Residence Time (MRT) From Zero to 72 hours Postdose (MRT0-72) of ADAMTS13 Activity and ADAMTS13 Antigen [ Time Frame: Pre-dose, 15 minutes, 1, 3, 9, 24, and 72 hours post dose ]
  MRT0-72 will be estimated for ADAMTS13 activity and ADAMTS13 antigen (ADAMTS13Ag) following SHP655 or placebo infusion in participants with both part A and part B.
• Area Under the Concentration (AUC) From Zero to Time of Last Quantifiable Concentration (AUC0-Last) of ADAMTS13 Activity and ADAMTS13 Antigen [ Time Frame: Pre-dose, 15 minutes, 1, 3, 9, 24, 72, 120, 168, 216, 288, and 744 hours post dose ]
  AUC0-last will be estimated for ADAMTS13 activity and ADAMTS13 antigen (ADAMTS13Ag) following SHP655 or placebo infusion in participants with both part A and part B.
• Area Under the Concentration-Time Curve (AUC) From Zero to 72 hours Postdose (AUC0-72) of ADAMTS13 Activity and ADAMTS13 Antigen [ Time Frame: Pre-dose, 15 minutes, 1, 3, 9, 24, and 72 hours post dose ]
  AUC0-72 will be estimated for ADAMTS13 activity and ADAMTS13 antigen (ADAMTS13Ag) following SHP655 or placebo infusion in participants with both part A and part B.
• Area Under the Concentration (AUC) From Zero to Infinite Time (AUC0-Inf) of ADAMTS13 Activity and ADAMTS13 Antigen [ Time Frame: Pre-dose, 15 minutes, 1, 3, 9, 24, 72, 120, 168, 216, 288, and 744 hours post dose ]
  AUC0-inf will be estimated for ADAMTS13 activity and ADAMTS13 antigen (ADAMTS13Ag) following SHP655 or placebo infusion in participants with both part A and part B.
• Systemic Clearance (CL) of ADAMTS13 Activity and ADAMTS13 Antigen [ Time Frame: Pre-dose, 15 minutes, 1, 3, 9, 24, 72, 120, 168, 216, 288, and 744 hours post dose ]
  Systemic clearance (CL) will be estimated for ADAMTS13 activity and ADAMTS13 antigen (ADAMTS13Ag) following SHP655 or placebo infusion in participants with both part A and part B.
• Volume of Distribution at Steady State (Vss) of ADAMTS13 Activity and ADAMTS13 Antigen. [ Time Frame: Pre-dose, 15 minutes, 1, 3, 9, 24, 72, 120, 168, 216, 288, and 744 hours post dose ]
  Vss will be estimated for ADAMTS13 activity and ADAMTS13 antigen (ADAMTS13Ag) following SHP655 or placebo infusion in participants with both part A and part B.
• Ultralarge Von Willebrand Factor (ULVWF) Percent [ Time Frame: Pre-dose, 15 minutes, 1, 3, 9, 24, 72, 120, 168, 216, 288, and 744 hours post dose ]
  Plasma ULVWF percent a PD variable will be observed in both part A and part B participants to evaluate the effect of SHP655 on VWF.
• Von Willebrand Factor:antigen (VWF:Ag) [ Time Frame: Pre-dose, 15 minutes, 1, 3, 9, 24, 72, 120, 168, 216, 288, and 744 hours post dose ]
  Plasma VWF:Ag a PD variable will be observed in both part A and part B participants to evaluate the effect of SHP655 on VWF.
• Von Willebrand Factor:Ristocetin cofactor activity (VWF:RCo) [ Time Frame: Pre-dose, 15 minutes, 1, 3, 9, 24, 72, 120, 168, 216, 288, and 744 hours post dose ]
  Plasma VWF:RCo a PD variable will be observed in both part A and part B participants to evaluate the effect of SHP655 on VWF.
• Plasma Free Hemoglobin [ Time Frame: Pre-dose, 15 minutes, 1, 3, 9, 24, 72, 120, 168, 216, 288, and 744 hours post dose ]
  The correlation of plasma free hemoglobin on SHP655 activity and VWF will be assessed in both part A and part B participants.
• Plasma Thrombospondin [ Time Frame: Pre-dose, 15 minutes, 1, 3, 9, 24, 72, 120, 168, 216, 288, and 744 hours post dose ]
  The correlation of plasma free thrombospondin levels on SHP655 activity and VWF will be assessed in both part A and part B participants.
• Time to Hospital Discharge Readiness [ Time Frame: Day 1, 2, 4, 6, 8, and 10 ]
  Time to discharge readiness is the time from Investigational product infusion until one of the following occurs: a sustained 15 point decrease on a linear 100 point VAS pain scale from baseline and transition to oral analgesia; or documentation in the participant chart that both participant and physician agreed that the participant was ready for hospital discharge; or written order for hospital discharge. Part B participants will be assessed in this outcome. Inpatient assessment will be assessed for every 4 hours while participant is awake.
• Change in Pain Score Assessed Using Visual Analog Scale (VAS) From the Last Assessment Prior to Investigational Product (IP) Infusion to 72 Hours Post Dose [ Time Frame: Pre-dose, 72 hours post dose ]
  VAS will be assessed to establish an efficacious dose range for acute VOC treatment (part B participants). Decrease in pain score assessed using 100-point Visual Analog Scale (VAS), the scale is 0-100, with 0 being no pain, and 100 being most severe.
• Pain Score Assessed Using Visual Analog Scale (VAS) Every 4 Hours (q4h) While Awake and Hospitalized [ Time Frame: From start of study treatment up to study completion (up to Day 31) ]
  VAS will be assessed to establish an efficacious dose range for acute VOC treatment (part B participants). On day day 1, 2, 4, 6, 8 and 10 VAS has to be assessed at all PK sampling time points if participant is awake. The study completion date is defined as the date on which the last participant in the study completes the final assessments. Decrease in pain score assessed using 100-point Visual Analog Scale (VAS), the scale is 0-100, with 0 being no pain, and 100 being most severe.

• Drug: SHP655
  Participants in both part A and part B of the study will receive SHP655 as a single IV infusion at one of the 3 dose levels of 40 IU/kg, 80 IU/kg, or 160 IU/kg for 12 days.
  Other Name: recombinant ADAMTS13
• Other: Placebo
  Participants will receive placebo matched to SHP655 of the 3 dose levels of 40 IU/kg, 80 IU/kg, and 160 IU/kg as single IV infusion in both part A and part B for 12 days.
• Other: Standard of Care (SoC)
  Participants will receive standard of care (SoC) treatment for acute VOC (part B) and either SHP655 or placebo as a single IV infusion of SHP655 or placebo at 3 dose levels of 40, 80, or 160 IU/kg for 12 days.

• Experimental: Part A
  Participants with baseline SCD receive a single dose of SHP655 or placebo matching to SHP655 intravenous (IV) infusion at 40, 80 and 160 International units per kilogram (IU/kg) in a dose escalation manner for 12 days.
  Interventions:

  • Drug: SHP655
  • Other: Placebo
• Experimental: Part B
  Participants with SCD and acute VOC requiring hospitalization will receive standard of care VOC treatment along with either SHP655 or placebo as a single IV infusion at one of the 3 dose levels of 40 IU/kg, 80 IU/kg, or 160 IU/kg for 12 days.
  Interventions:

  • Drug: SHP655
  • Other: Placebo
  • Other: Standard of Care (SoC)

Inclusion Criteria:

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.

Exclusion Criteria:

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.