A Study of PEGylated Recombinant Human Hyaluronidase in Combination With Nab-Paclitaxel Plus Gemcitabine Compared With Placebo Plus Nab-Paclitaxel and Gemcitabine in Participants With Hyaluronan-High Stage IV Previously Untreated Pancreatic Ductal Adenocarcinoma

Inclusion criteria: Participants must satisfy all the following inclusion criteria to be enrolled in the study:

1. Signed, written Institutional Review Board/Ethics Committee-approved Informed ConsentForm (ICF).

2. Stage IV PDA with histological or cytological confirmation of PDA.

3. Participants must be determined to be HA-high based on archived or fresh tumor corebiopsy or sample obtained after the participant has documented metastatic disease.Biopsies/samples must meet the following requirements:

4. Pancreas tumor biopsies/samples obtained on or after the date that metastaticdisease is documented or tumor biopsies/samples from a metastatic lesion areacceptable.

5. Tumor biopsies or samples must meet the requirements provided in the StudyLaboratory Manual with regard to tumor tissue architecture. Note: cytologysamples from fine needle aspirates without maintained tissue architecture orbrushing biopsies are not acceptable.

6. Tumor tissue (formalin-fixed paraffin-embedded [FFPE] block preferred) mustinclude enough tumor to make a minimum of 5-10 unstained, consecutive FFPE slides (10 slides are preferred) of 1 archival block that meet specific tissue samplerequirements.

7. Radiographic confirmation of Stage IV PDA with at least 1 tumor metastasis measurableon computed tomography (CT) scan or magnetic resonance imaging (MRI) per ResponseEvaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria, excluding theprimary pancreatic lesion.

8. If a participant has had adjuvant/neoadjuvant therapy and/or therapy for locallyadvanced disease (chemotherapy for non-metastatic pancreatic cancer in combinationwith or without radiation therapy), tumor recurrence or disease progression must haveoccurred no sooner than 6 months after completing the last dose of the aforementionedtherapies, provided all toxicities have returned to baseline or less than or equal to (≤) Grade 1.

9. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.

10. Life expectancy greater than or equal to (≥) 3 months.

11. Age ≥18 years.

12. A negative urine or serum pregnancy test within 7 days before Cycle 1, Day 1 (C1D1;first dose of study medication) if female participant is of childbearing potential.

13. Screening clinical laboratory values as follows:

14. Total bilirubin ≤1.5 times upper limit of normal (ULN) (participants with Gilbertsyndrome are eligible independent of bilirubin levels).

15. Aspartate aminotransferase (serum glutamic oxaloacetic transaminase) and alanineaminotransferase (serum glutamic pyruvate transaminase) ≤2.5 times ULN, (if livermetastases are present, then ≤5 times ULN is allowed).

16. Serum creatinine ≤2.0 milligrams/deciliter (mg/dL) or calculated creatinineclearance ≥40 milliliters/minute (mL/min).

17. Serum albumin ≥2.5 grams/deciliter (g/dL).

18. Prothrombin time or international normalized ratio (INR) within normal limits (±15%), unless participant takes warfarin, in which case prothrombin time or INRresult must be within therapeutic range.

19. Partial thromboplastin time (PTT) within normal limits (±15%).

20. Hemoglobin ≥9 g/dL (transfusion and erythropoietic agents allowed).

21. Absolute neutrophil count ≥1,500 cells/cubic millimeter (cells/mm^3).

22. Platelet count ≥100,000/mm^3.

23. For women of childbearing potential (WOCBP) and for men, agreement to use a highlyeffective contraceptive method from the time of screening throughout the study until 1month (WOCBP) or 6 months (men) after administration of the last dose of any studymedication. Highly effective contraceptive methods consist of prior sterilization,intrauterine device (IUD), intrauterine hormone-releasing system (IUS), oral orinjectable contraceptives, barrier methods, and/or true sexual abstinence.

Exclusion criteria: Participants are ineligible for enrollment if they meet any of the following exclusioncriteria:

1. Clinical evidence of deep vein thrombosis (DVT), pulmonary embolism (PE) or otherknown thromboembolic (TE) event present during the screening period.

2. Participants with superficial vein thrombosis are eligible.

3. Participants with visceral/splanchnic vein thrombosis are still eligible if, inthe opinion of the Investigator, the visceral/splanchnic vein thrombosis isprimarily associated with the anatomic location of the underlying disease ofmetastatic pancreatic cancer (there must be primary or metastatic disease inreasonable proximity to the thrombosis, and the Investigator determines that thethrombosis is due to a local tumor event and not a coagulation issue).

4. Previous radiotherapy, surgery, chemotherapy, or investigational therapy for thetreatment of metastatic disease. a. Palliative radiotherapy for pain control of metastatic bone lesions is allowed.

5. Known central nervous system involvement or brain metastases.

6. New York Heart Association Class III or IV cardiac disease or myocardial infarctionwithin the past 12 months.

7. History of cerebrovascular accident or transient ischemic attack.

8. Clinically significant pre-existing carotid artery disease.

9. Known infection with human immunodeficiency virus, or active infection with hepatitisB or hepatitis C within the past 12 months.

10. Known allergy to hyaluronidase.

11. Current use of megestrol acetate or megestrol acetate-containing drugs (use within 10days of Day 1).

12. Contraindication to heparin as per institutional guidelines.

13. Women currently pregnant or breastfeeding.

14. Intolerance to dexamethasone.

15. History of another primary cancer within the last 3 years with the exception ofnon-melanoma skin cancer, early-stage prostate cancer, or curatively treated cervicalcarcinoma in-situ.

16. Any other disease, active, uncontrolled bacterial, viral or fungal infection requiringsystemic therapy, metabolic dysfunction, physical examination finding or clinicallaboratory finding that leads to reasonable suspicion of a disease or condition thatcontraindicates the use of an investigational drug, or that may affect theinterpretation of the results, or that may render the participant at high risk fortreatment complications.

17. Immunization with a live vaccine up to 2 weeks prior to Day 1.

18. Hypersensitivity to the active substance or ingredients of PEGPH20, gemcitabine, andnab-paclitaxel.

19. Inability to comply with study and follow-up procedures as judged by the Investigator.