Trial Outcomes & Findings for 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 (NCT NCT02715804)

Last Updated: 2020-07-14

Results Overview

Overall survival was defined as the time from randomization until death from any cause. Overall survival was analyzed using Kaplan-Meier methods.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

492 participants

Primary outcome timeframe

From randomization until death from any cause (maximum exposure: 150.1 weeks for PAG, and 83.9 weeks for AG)

Results posted on

2020-07-14

Participant Flow

A total of 492 participants were enrolled from 14 March 2016 through 26 December 2018 in 20 countries.

A total of 492 participants were enrolled and randomized in 2:1 ratio to received either PAG (PEGPH20 + Nab-paclitaxel + Gemcitabine) or AG (Placebo + Nab-paclitaxel + Gemcitabine).

Participant milestones

Participant milestones
Measure	PAG: PEGPH20 + Nab-Paclitaxel + Gemcitabine Participants received 3.0 micrograms/kilogram (μg/kg) PEGPH20 as an intravenous (IV) infusion, twice weekly for Weeks 1 to 3 of Cycle 1 (each cycle consisted of 4 weeks \[Week 4 of every cycle was a rest week with no treatment\]), then once weekly for Weeks 1 to 3 of Cycle 2 and beyond in combination with 125 milligrams/square meter (mg/m\^2) nab-paclitaxel as an IV infusion and 1000 mg/m\^2 gemcitabine as an IV infusion, once weekly for Weeks 1 to 3 of all treatment cycles. Treatment was continued until disease progression, unacceptable toxicity, death, or withdrawal of consent (Maximum exposure: 150.1 weeks).	AG: Placebo + Nab-Paclitaxel + Gemcitabine Participants received placebo matching to PEGPH20 as an IV infusion, twice weekly for Weeks 1 to 3 of Cycle 1 (each cycle consisting of 4 weeks \[Week 4 of every cycle will be a rest week with no treatment\]), then once weekly for Weeks 1 to 3 of Cycle 2 and beyond in combination with 125 mg/m\^2 nab-paclitaxel as an IV infusion and 1000 mg/m\^2 gemcitabine as an IV infusion, once weekly for Weeks 1 to 3 of all treatment cycles. Treatment was continued until disease progression, unacceptable toxicity, death, or withdrawal of consent (Maximum exposure: 83.9 weeks).
Overall Study STARTED	327	165
Overall Study Received at Least 1 Dose of Study Drug	323	158
Overall Study Safety Population	325	156
Overall Study COMPLETED	98	52
Overall Study NOT COMPLETED	229	113

Reasons for withdrawal

Reasons for withdrawal
Measure	PAG: PEGPH20 + Nab-Paclitaxel + Gemcitabine Participants received 3.0 micrograms/kilogram (μg/kg) PEGPH20 as an intravenous (IV) infusion, twice weekly for Weeks 1 to 3 of Cycle 1 (each cycle consisted of 4 weeks \[Week 4 of every cycle was a rest week with no treatment\]), then once weekly for Weeks 1 to 3 of Cycle 2 and beyond in combination with 125 milligrams/square meter (mg/m\^2) nab-paclitaxel as an IV infusion and 1000 mg/m\^2 gemcitabine as an IV infusion, once weekly for Weeks 1 to 3 of all treatment cycles. Treatment was continued until disease progression, unacceptable toxicity, death, or withdrawal of consent (Maximum exposure: 150.1 weeks).	AG: Placebo + Nab-Paclitaxel + Gemcitabine Participants received placebo matching to PEGPH20 as an IV infusion, twice weekly for Weeks 1 to 3 of Cycle 1 (each cycle consisting of 4 weeks \[Week 4 of every cycle will be a rest week with no treatment\]), then once weekly for Weeks 1 to 3 of Cycle 2 and beyond in combination with 125 mg/m\^2 nab-paclitaxel as an IV infusion and 1000 mg/m\^2 gemcitabine as an IV infusion, once weekly for Weeks 1 to 3 of all treatment cycles. Treatment was continued until disease progression, unacceptable toxicity, death, or withdrawal of consent (Maximum exposure: 83.9 weeks).
Overall Study Death	222	106
Overall Study Withdrawal by Subject	5	4
Overall Study Other than specified	2	3

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	PAG: PEGPH20 + Nab-Paclitaxel + Gemcitabine n=327 Participants Participants received 3.0 μg/kg PEGPH20 as an IV infusion, twice weekly for Weeks 1 to 3 of Cycle 1 (each cycle consisted of 4 weeks \[Week 4 of every cycle was a rest week with no treatment\]), then once weekly for Weeks 1 to 3 of Cycle 2 and beyond in combination with 125 mg/m\^2 nab-paclitaxel as an IV infusion and 1000 mg/m\^2 gemcitabine as an IV infusion, once weekly for Weeks 1 to 3 of all treatment cycles. Treatment was continued until disease progression, unacceptable toxicity, death, or withdrawal of consent (Maximum exposure: 150.1 weeks).	AG: Placebo + Nab-Paclitaxel + Gemcitabine n=165 Participants Participants received placebo matching to PEGPH20 as an IV infusion, twice weekly for Weeks 1 to 3 of Cycle 1 (each cycle consisting of 4 weeks \[Week 4 of every cycle will be a rest week with no treatment\]), then once weekly for Weeks 1 to 3 of Cycle 2 and beyond in combination with 125 mg/m\^2 nab-paclitaxel as an IV infusion and 1000 mg/m\^2 gemcitabine as an IV infusion, once weekly for Weeks 1 to 3 of all treatment cycles. Treatment was continued until disease progression, unacceptable toxicity, death, or withdrawal of consent (Maximum exposure: 83.9 weeks).	Total n=492 Participants Total of all reporting groups
Age, Continuous	63.8 years STANDARD_DEVIATION 9.62 • n=5 Participants	62.3 years STANDARD_DEVIATION 9.50 • n=7 Participants	63.3 years STANDARD_DEVIATION 9.60 • n=5 Participants
Sex: Female, Male Female	147 Participants n=5 Participants	85 Participants n=7 Participants	232 Participants n=5 Participants
Sex: Female, Male Male	180 Participants n=5 Participants	80 Participants n=7 Participants	260 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	24 Participants n=5 Participants	11 Participants n=7 Participants	35 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	267 Participants n=5 Participants	138 Participants n=7 Participants	405 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	36 Participants n=5 Participants	16 Participants n=7 Participants	52 Participants n=5 Participants
Race/Ethnicity, Customized White/Caucasian	266 Participants n=5 Participants	126 Participants n=7 Participants	392 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	11 Participants n=5 Participants	5 Participants n=7 Participants	16 Participants n=5 Participants
Race/Ethnicity, Customized Asian	33 Participants n=5 Participants	24 Participants n=7 Participants	57 Participants n=5 Participants
Race/Ethnicity, Customized Other	17 Participants n=5 Participants	10 Participants n=7 Participants	27 Participants n=5 Participants

PRIMARY outcome

Timeframe: From randomization until death from any cause (maximum exposure: 150.1 weeks for PAG, and 83.9 weeks for AG)

Population: ITT population included all randomized participants.

Overall survival was defined as the time from randomization until death from any cause. Overall survival was analyzed using Kaplan-Meier methods.

Outcome measures

Outcome measures
Measure	PAG: PEGPH20 + Nab-Paclitaxel + Gemcitabine n=327 Participants Participants received 3.0 μg/kg PEGPH20 as an IV infusion, twice weekly for Weeks 1 to 3 of Cycle 1 (each cycle consisted of 4 weeks \[Week 4 of every cycle was a rest week with no treatment\]), then once weekly for Weeks 1 to 3 of Cycle 2 and beyond in combination with 125 mg/m\^2 nab-paclitaxel as an IV infusion and 1000 mg/m\^2 gemcitabine as an IV infusion, once weekly for Weeks 1 to 3 of all treatment cycles. Treatment was continued until disease progression, unacceptable toxicity, death, or withdrawal of consent (Maximum exposure: 150.1 weeks).	AG: Placebo + Nab-Paclitaxel + Gemcitabine n=165 Participants Participants received placebo matching to PEGPH20 as an IV infusion, twice weekly for Weeks 1 to 3 of Cycle 1 (each cycle consisting of 4 weeks \[Week 4 of every cycle will be a rest week with no treatment\]), then once weekly for Weeks 1 to 3 of Cycle 2 and beyond in combination with 125 mg/m\^2 nab-paclitaxel as an IV infusion and 1000 mg/m\^2 gemcitabine as an IV infusion, once weekly for Weeks 1 to 3 of all treatment cycles. Treatment was continued until disease progression, unacceptable toxicity, death, or withdrawal of consent (Maximum exposure: 83.9 weeks).
Overall Survival	11.2 months Interval 10.3 to 12.3	11.5 months Interval 9.0 to 12.5

SECONDARY outcome

Timeframe: From the date of randomization until disease progression or death from any cause (maximum exposure: 150.1 weeks for PAG, and 83.9 weeks for AG)

Population: ITT population included all randomized participants.

PFS was defined as the time from randomization until the first occurrence of radiological disease progression, as determined by the blinded Central Imaging Vendor (CIV) based on Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1, or death from any cause during the treatment period. Disease progression was defined as at least a 20 percent (%) increase in sum of diameters of target lesions, taking as reference the smallest sum on study thus far, nadir (this included baseline sum if that was the smallest on study); Sum must also demonstrate an absolute increase of at least 5 millimeters (mm); Appearance of one or more new lesions; Unequivocal progression of existing non-target lesions. Surviving participants without disease progression were censored for PFS analysis at the date of last evaluable post-baseline tumor assessment. Surviving participants without any post-baseline disease assessment were censored on Day 1. PFS was estimated using Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	PAG: PEGPH20 + Nab-Paclitaxel + Gemcitabine n=327 Participants Participants received 3.0 μg/kg PEGPH20 as an IV infusion, twice weekly for Weeks 1 to 3 of Cycle 1 (each cycle consisted of 4 weeks \[Week 4 of every cycle was a rest week with no treatment\]), then once weekly for Weeks 1 to 3 of Cycle 2 and beyond in combination with 125 mg/m\^2 nab-paclitaxel as an IV infusion and 1000 mg/m\^2 gemcitabine as an IV infusion, once weekly for Weeks 1 to 3 of all treatment cycles. Treatment was continued until disease progression, unacceptable toxicity, death, or withdrawal of consent (Maximum exposure: 150.1 weeks).	AG: Placebo + Nab-Paclitaxel + Gemcitabine n=165 Participants Participants received placebo matching to PEGPH20 as an IV infusion, twice weekly for Weeks 1 to 3 of Cycle 1 (each cycle consisting of 4 weeks \[Week 4 of every cycle will be a rest week with no treatment\]), then once weekly for Weeks 1 to 3 of Cycle 2 and beyond in combination with 125 mg/m\^2 nab-paclitaxel as an IV infusion and 1000 mg/m\^2 gemcitabine as an IV infusion, once weekly for Weeks 1 to 3 of all treatment cycles. Treatment was continued until disease progression, unacceptable toxicity, death, or withdrawal of consent (Maximum exposure: 83.9 weeks).
Progression-Free Survival (PFS)	7.1 months Interval 5.5 to 7.4	7.1 months Interval 4.8 to 8.3

SECONDARY outcome

Timeframe: From the date of randomization until CR or PR (maximum exposure: 150.1 weeks for PAG, and 83.9 weeks for AG)

Population: ITT population included all randomized participants.

ORR was defined as percentage of participants who achieved either a complete response (CR) or partial response (PR) as determined by the blinded CIV based on RECIST version 1.1. CR was defined as disappearance of all target and non-target lesions; Any pathological or non-pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<) 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Outcome measures

Outcome measures
Measure	PAG: PEGPH20 + Nab-Paclitaxel + Gemcitabine n=327 Participants Participants received 3.0 μg/kg PEGPH20 as an IV infusion, twice weekly for Weeks 1 to 3 of Cycle 1 (each cycle consisted of 4 weeks \[Week 4 of every cycle was a rest week with no treatment\]), then once weekly for Weeks 1 to 3 of Cycle 2 and beyond in combination with 125 mg/m\^2 nab-paclitaxel as an IV infusion and 1000 mg/m\^2 gemcitabine as an IV infusion, once weekly for Weeks 1 to 3 of all treatment cycles. Treatment was continued until disease progression, unacceptable toxicity, death, or withdrawal of consent (Maximum exposure: 150.1 weeks).	AG: Placebo + Nab-Paclitaxel + Gemcitabine n=165 Participants Participants received placebo matching to PEGPH20 as an IV infusion, twice weekly for Weeks 1 to 3 of Cycle 1 (each cycle consisting of 4 weeks \[Week 4 of every cycle will be a rest week with no treatment\]), then once weekly for Weeks 1 to 3 of Cycle 2 and beyond in combination with 125 mg/m\^2 nab-paclitaxel as an IV infusion and 1000 mg/m\^2 gemcitabine as an IV infusion, once weekly for Weeks 1 to 3 of all treatment cycles. Treatment was continued until disease progression, unacceptable toxicity, death, or withdrawal of consent (Maximum exposure: 83.9 weeks).
Objective Response Rate (ORR): Percentage of Participants With Objective Response	47.1 percentage of participants Interval 41.6 to 52.7	36.4 percentage of participants Interval 29.0 to 44.2

SECONDARY outcome

Timeframe: From date of first objective response (CR or PR) until date of first disease progression (maximum exposure: 150.1 weeks for PAG, and 83.9 weeks for AG)

Population: ITT population included all randomized participants. Here, 'Overall number of participants analyzed' signifies participants with objective response.

DOR was defined as the time from the first objective response of CR or PR until disease progression (as determined by the blinded CIV based on RECIST version 1.1) or death within 14 days of last dose of study treatment or randomization. CR was defined as disappearance of all target and non-target lesions; Any pathological or non-pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Disease progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study thus far, the sum must also demonstrate an absolute increase of at least 5 mm, or the appearance of one or more new lesions; and unequivocal progression of existing non-target lesions. DOR was analyzed using Kaplan-Meier methods.

Outcome measures

Outcome measures
Measure	PAG: PEGPH20 + Nab-Paclitaxel + Gemcitabine n=154 Participants Participants received 3.0 μg/kg PEGPH20 as an IV infusion, twice weekly for Weeks 1 to 3 of Cycle 1 (each cycle consisted of 4 weeks \[Week 4 of every cycle was a rest week with no treatment\]), then once weekly for Weeks 1 to 3 of Cycle 2 and beyond in combination with 125 mg/m\^2 nab-paclitaxel as an IV infusion and 1000 mg/m\^2 gemcitabine as an IV infusion, once weekly for Weeks 1 to 3 of all treatment cycles. Treatment was continued until disease progression, unacceptable toxicity, death, or withdrawal of consent (Maximum exposure: 150.1 weeks).	AG: Placebo + Nab-Paclitaxel + Gemcitabine n=60 Participants Participants received placebo matching to PEGPH20 as an IV infusion, twice weekly for Weeks 1 to 3 of Cycle 1 (each cycle consisting of 4 weeks \[Week 4 of every cycle will be a rest week with no treatment\]), then once weekly for Weeks 1 to 3 of Cycle 2 and beyond in combination with 125 mg/m\^2 nab-paclitaxel as an IV infusion and 1000 mg/m\^2 gemcitabine as an IV infusion, once weekly for Weeks 1 to 3 of all treatment cycles. Treatment was continued until disease progression, unacceptable toxicity, death, or withdrawal of consent (Maximum exposure: 83.9 weeks).
Duration of Response (DOR)	6.1 months Interval 5.5 to 7.8	7.4 months Interval 5.3 to 9.4

SECONDARY outcome

Timeframe: From administration of first dose of study drug up to 30 days after last dose of study drug (maximum exposure: 150.1 weeks for PAG, and 83.9 weeks for AG)

Population: Safety population included all participants who received at least 1 dose of study medication, and analyzed according to the treatment they actually received.

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs were defined as AEs that begin or worsen in severity during or after the participant's first dose of study treatment and no later than 30 days after the date of the last dose of study treatment and/or any treatment-related AE regardless of the onset date. AEs included both SAEs and non-serious AEs. A summary of other non-serious AEs and all SAEs, regardless of causality is located in the 'Reported AE section'.

Outcome measures

Outcome measures
Measure	PAG: PEGPH20 + Nab-Paclitaxel + Gemcitabine n=325 Participants Participants received 3.0 μg/kg PEGPH20 as an IV infusion, twice weekly for Weeks 1 to 3 of Cycle 1 (each cycle consisted of 4 weeks \[Week 4 of every cycle was a rest week with no treatment\]), then once weekly for Weeks 1 to 3 of Cycle 2 and beyond in combination with 125 mg/m\^2 nab-paclitaxel as an IV infusion and 1000 mg/m\^2 gemcitabine as an IV infusion, once weekly for Weeks 1 to 3 of all treatment cycles. Treatment was continued until disease progression, unacceptable toxicity, death, or withdrawal of consent (Maximum exposure: 150.1 weeks).	AG: Placebo + Nab-Paclitaxel + Gemcitabine n=156 Participants Participants received placebo matching to PEGPH20 as an IV infusion, twice weekly for Weeks 1 to 3 of Cycle 1 (each cycle consisting of 4 weeks \[Week 4 of every cycle will be a rest week with no treatment\]), then once weekly for Weeks 1 to 3 of Cycle 2 and beyond in combination with 125 mg/m\^2 nab-paclitaxel as an IV infusion and 1000 mg/m\^2 gemcitabine as an IV infusion, once weekly for Weeks 1 to 3 of all treatment cycles. Treatment was continued until disease progression, unacceptable toxicity, death, or withdrawal of consent (Maximum exposure: 83.9 weeks).
Number of Participants With Treatment-Emergent Adverse Events (AEs)	325 Participants	156 Participants

SECONDARY outcome

Timeframe: From administration of first dose of study drug up to 30 days after last dose of study drug (maximum exposure: 150.1 weeks for PAG, and 83.9 weeks for AG)

Population: Safety population included all participants who received at least 1 dose of study medication, and analyzed according to the treatment they actually received. Here, 'Number analyzed' signifies participants evaluable for specified categories.

Severity grade associated with a laboratory parameter value was determined using Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03. Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life-threatening. Grade 0 indicates evaluable lab records but not fall into any CTCAE grade for certain CTCAE term. A worst post-baseline grade shift was defined as the worst change that occurred at any measured timepoint during study. Hematology abnormalities: anemia(hemoglobin decreased), lymphocyte count decreased, lymphocyte count increased, neutropenia(neutrophil count decreased), thrombocytopenia(platelet count decreased), and leukopenia(white blood cell decreased). Chemistry abnormalities: hypoalbuminemia, alkaline phosphatase increased, alanine aminotransferase increased, aspartate aminotransferase increased, hyperbilirubinemia, hypo- and hypercalcemia, creatinine increased, hypo- and hyperglycaemia, hypo- and hyperkalemia, hypo- and hypermagnesemia, hypo- and hypernatremia.

Outcome measures

Outcome measures
Measure	PAG: PEGPH20 + Nab-Paclitaxel + Gemcitabine n=325 Participants Participants received 3.0 μg/kg PEGPH20 as an IV infusion, twice weekly for Weeks 1 to 3 of Cycle 1 (each cycle consisted of 4 weeks \[Week 4 of every cycle was a rest week with no treatment\]), then once weekly for Weeks 1 to 3 of Cycle 2 and beyond in combination with 125 mg/m\^2 nab-paclitaxel as an IV infusion and 1000 mg/m\^2 gemcitabine as an IV infusion, once weekly for Weeks 1 to 3 of all treatment cycles. Treatment was continued until disease progression, unacceptable toxicity, death, or withdrawal of consent (Maximum exposure: 150.1 weeks).	AG: Placebo + Nab-Paclitaxel + Gemcitabine n=156 Participants Participants received placebo matching to PEGPH20 as an IV infusion, twice weekly for Weeks 1 to 3 of Cycle 1 (each cycle consisting of 4 weeks \[Week 4 of every cycle will be a rest week with no treatment\]), then once weekly for Weeks 1 to 3 of Cycle 2 and beyond in combination with 125 mg/m\^2 nab-paclitaxel as an IV infusion and 1000 mg/m\^2 gemcitabine as an IV infusion, once weekly for Weeks 1 to 3 of all treatment cycles. Treatment was continued until disease progression, unacceptable toxicity, death, or withdrawal of consent (Maximum exposure: 83.9 weeks).
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Anemia: Post-baseline · Grade 0	6 Participants	3 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Anemia: Post-baseline · Grade 1	84 Participants	41 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Anemia: Post-baseline · Grade 2	164 Participants	74 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Anemia: Post-baseline · Grade 3	67 Participants	37 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Anemia: Post-baseline · Grade 4	0 Participants	0 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Lymphocyte count decreased: Post-baseline · Grade 0	33 Participants	17 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Lymphocyte count decreased: Post-baseline · Grade 1	83 Participants	46 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Lymphocyte count decreased: Post-baseline · Grade 2	102 Participants	46 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Lymphocyte count decreased: Post-baseline · Grade 3	90 Participants	40 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Lymphocyte count decreased: Post-baseline · Grade 4	13 Participants	6 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Lymphocyte count increased: Post-baseline · Grade 0	302 Participants	150 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Lymphocyte count increased: Post-baseline · Grade 1	0 Participants	0 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Lymphocyte count increased: Post-baseline · Grade 2	19 Participants	5 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Lymphocyte count increased: Post-baseline · Grade 3	0 Participants	0 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Lymphocyte count increased: Post-baseline · Grade 4	0 Participants	0 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Neutropenia: Post-baseline · Grade 0	85 Participants	31 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Neutropenia: Post-baseline · Grade 1	27 Participants	11 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Neutropenia: Post-baseline · Grade 2	57 Participants	30 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Neutropenia: Post-baseline · Grade 3	98 Participants	48 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Neutropenia: Post-baseline · Grade 4	54 Participants	35 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Thrombocytopenia: Post-baseline · Grade 0	52 Participants	32 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Thrombocytopenia: Post-baseline · Grade 1	134 Participants	63 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Thrombocytopenia: Post-baseline · Grade 2	76 Participants	36 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Thrombocytopenia: Post-baseline · Grade 3	51 Participants	20 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Thrombocytopenia: Post-baseline · Grade 4	9 Participants	4 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Leukopenia: Post-baseline · Grade 0	74 Participants	32 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Leukopenia: Post-baseline · Grade 1	30 Participants	15 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Leukopenia: Post-baseline · Grade 2	100 Participants	43 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Leukopenia: Post-baseline · Grade 3	87 Participants	51 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Leukopenia: Post-baseline · Grade 4	30 Participants	14 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Hypoalbuminemia (Albumin): Post-baseline · Grade 0	19 Participants	46 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Hypoalbuminemia (Albumin): Post-baseline · Grade 1	102 Participants	62 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Hypoalbuminemia (Albumin): Post-baseline · Grade 2	185 Participants	44 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Hypoalbuminemia (Albumin): Post-baseline · Grade 3	12 Participants	3 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Hypoalbuminemia (Albumin): Post-baseline · Grade 4	0 Participants	0 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Alkaline phosphatase increased: Post-baseline · Grade 0	135 Participants	57 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Alkaline phosphatase increased: Post-baseline · Grade 1	114 Participants	62 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Alkaline phosphatase increased: Post-baseline · Grade 2	50 Participants	26 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Alkaline phosphatase increased: Post-baseline · Grade 3	19 Participants	10 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Alkaline phosphatase increased: Post-baseline · Grade 4	0 Participants	0 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Alanine aminotransferase increased: Post-baseline · Grade 0	69 Participants	33 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Alanine aminotransferase increased: Post-baseline · Grade 1	155 Participants	72 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Alanine aminotransferase increased: Post-baseline · Grade 2	43 Participants	32 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Alanine aminotransferase increased: Post-baseline · Grade 3	51 Participants	17 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Alanine aminotransferase increased: Post-baseline · Grade 4	0 Participants	1 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Aspartate aminotransferase increased:Post-baseline · Grade 0	77 Participants	28 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Aspartate aminotransferase increased:Post-baseline · Grade 1	168 Participants	96 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Aspartate aminotransferase increased:Post-baseline · Grade 2	49 Participants	17 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Aspartate aminotransferase increased:Post-baseline · Grade 3	25 Participants	13 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Aspartate aminotransferase increased:Post-baseline · Grade 4	0 Participants	1 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Hyperbilirubinemia: Post-baseline · Grade 0	237 Participants	125 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Hyperbilirubinemia: Post-baseline · Grade 1	36 Participants	9 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Hyperbilirubinemia: Post-baseline · Grade 2	31 Participants	15 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Hyperbilirubinemia: Post-baseline · Grade 3	12 Participants	6 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Hyperbilirubinemia: Post-baseline · Grade 4	3 Participants	0 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Hypocalcemia (calcium): Post-baseline · Grade 0	224 Participants	119 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Hypocalcemia (calcium): Post-baseline · Grade 1	68 Participants	30 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Hypocalcemia (calcium): Post-baseline · Grade 2	22 Participants	6 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Hypocalcemia (calcium): Post-baseline · Grade 3	4 Participants	0 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Hypocalcemia (calcium): Post-baseline · Grade 4	0 Participants	0 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Hypercalcemia (calcium): Post-baseline · Grade 0	278 Participants	148 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Hypercalcemia (calcium): Post-baseline · Grade 1	34 Participants	6 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Hypercalcemia (calcium): Post-baseline · Grade 2	3 Participants	0 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Hypercalcemia (calcium): Post-baseline · Grade 3	3 Participants	1 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Hypercalcemia (calcium): Post-baseline · Grade 4	0 Participants	0 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Creatinine increased: Post-baseline · Grade 0	267 Participants	135 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Creatinine increased: Post-baseline · Grade 1	45 Participants	16 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Creatinine increased: Post-baseline · Grade 2	6 Participants	4 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Creatinine increased: Post-baseline · Grade 3	0 Participants	0 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Creatinine increased: Post-baseline · Grade 4	0 Participants	0 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Hypoglycemia (glucose): Post-baseline · Grade 0	292 Participants	140 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Hypoglycemia (glucose): Post-baseline · Grade 1	17 Participants	9 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Hypoglycemia (glucose): Post-baseline · Grade 2	7 Participants	1 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Hypoglycemia (glucose): Post-baseline · Grade 3	3 Participants	1 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Hypoglycemia (glucose): Post-baseline · Grade 4	1 Participants	4 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Hyperglycemia (glucose): Post-baseline · Grade 0	31 Participants	24 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Hyperglycemia (glucose): Post-baseline · Grade 1	90 Participants	45 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Hyperglycemia (glucose): Post-baseline · Grade 2	119 Participants	44 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Hyperglycemia (glucose): Post-baseline · Grade 3	76 Participants	40 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Hyperglycemia (glucose): Post-baseline · Grade 4	4 Participants	2 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Hypokalemia (potassium): Post-baseline · Grade 0	202 Participants	104 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Hypokalemia (potassium): Post-baseline · Grade 1	89 Participants	38 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Hypokalemia (potassium): Post-baseline · Grade 2	0 Participants	0 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Hypokalemia (potassium): Post-baseline · Grade 3	24 Participants	11 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Hypokalemia (potassium): Post-baseline · Grade 4	4 Participants	2 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Hyperkalemia (potassium): Post-baseline · Grade 0	245 Participants	122 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Hyperkalemia (potassium): Post-baseline · Grade 1	44 Participants	19 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Hyperkalemia (potassium): Post-baseline · Grade 2	21 Participants	11 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Hyperkalemia (potassium): Post-baseline · Grade 3	7 Participants	3 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Hyperkalemia (potassium): Post-baseline · Grade 4	2 Participants	0 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Hypomagnesemia (magnesium): Post-baseline · Grade 0	209 Participants	113 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Hypomagnesemia (magnesium): Post-baseline · Grade 1	95 Participants	36 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Hypomagnesemia (magnesium): Post-baseline · Grade 2	9 Participants	5 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Hypomagnesemia (magnesium): Post-baseline · Grade 3	4 Participants	0 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Hypomagnesemia (magnesium): Post-baseline · Grade 4	1 Participants	0 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Hypermagnesemia (magnesium): Post-baseline · Grade 0	306 Participants	150 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Hypermagnesemia (magnesium): Post-baseline · Grade 1	8 Participants	4 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Hypermagnesemia (magnesium): Post-baseline · Grade 2	0 Participants	0 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Hypermagnesemia (magnesium): Post-baseline · Grade 3	4 Participants	0 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Hypermagnesemia (magnesium): Post-baseline · Grade 4	0 Participants	0 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Hyponatremia (sodium): Post-baseline · Grade 0	96 Participants	49 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Hyponatremia (sodium): Post-baseline · Grade 1	167 Participants	85 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Hyponatremia (sodium): Post-baseline · Grade 2	0 Participants	0 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Hyponatremia (sodium): Post-baseline · Grade 3	54 Participants	21 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Hyponatremia (sodium): Post-baseline · Grade 4	1 Participants	0 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Hypernatremia (sodium): Post-baseline · Grade 0	308 Participants	153 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Hypernatremia (sodium): Post-baseline · Grade 1	9 Participants	2 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Hypernatremia (sodium): Post-baseline · Grade 2	0 Participants	0 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Hypernatremia (sodium): Post-baseline · Grade 3	0 Participants	0 Participants
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study Hypernatremia (sodium): Post-baseline · Grade 4	1 Participants	0 Participants

SECONDARY outcome

Timeframe: From administration of first dose of study drug up to 30 days after last dose of study drug (maximum exposure: 150.1 weeks for PAG, and 83.9 weeks for AG)

Population: Safety population included all participants who received at least 1 dose of study medication, and analyzed according to the treatment they actually received.

ECGs including clinical significance was evaluated by the Investigator. Criteria for clinical significance were as per investigator's discretion.

Outcome measures

Outcome measures
Measure	PAG: PEGPH20 + Nab-Paclitaxel + Gemcitabine n=325 Participants Participants received 3.0 μg/kg PEGPH20 as an IV infusion, twice weekly for Weeks 1 to 3 of Cycle 1 (each cycle consisted of 4 weeks \[Week 4 of every cycle was a rest week with no treatment\]), then once weekly for Weeks 1 to 3 of Cycle 2 and beyond in combination with 125 mg/m\^2 nab-paclitaxel as an IV infusion and 1000 mg/m\^2 gemcitabine as an IV infusion, once weekly for Weeks 1 to 3 of all treatment cycles. Treatment was continued until disease progression, unacceptable toxicity, death, or withdrawal of consent (Maximum exposure: 150.1 weeks).	AG: Placebo + Nab-Paclitaxel + Gemcitabine n=156 Participants Participants received placebo matching to PEGPH20 as an IV infusion, twice weekly for Weeks 1 to 3 of Cycle 1 (each cycle consisting of 4 weeks \[Week 4 of every cycle will be a rest week with no treatment\]), then once weekly for Weeks 1 to 3 of Cycle 2 and beyond in combination with 125 mg/m\^2 nab-paclitaxel as an IV infusion and 1000 mg/m\^2 gemcitabine as an IV infusion, once weekly for Weeks 1 to 3 of all treatment cycles. Treatment was continued until disease progression, unacceptable toxicity, death, or withdrawal of consent (Maximum exposure: 83.9 weeks).
Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG)	8 Participants	4 Participants

SECONDARY outcome

Timeframe: From administration of first dose of study drug up to 30 days after last dose of study drug (maximum exposure: 150.1 weeks for PAG, and 83.9 weeks for AG)

Population: Safety population included all participants who received at least 1 dose of study medication, and analyzed according to the treatment they actually received.

Vital signs included measurement of blood pressure (systolic blood pressure \[SBP\] and diastolic blood pressure \[DBP\]), heart rate, and body weight. Criteria for clinical significance abnormalities were: Heart rate: \<50 beats per minute (bpm), \>120 bpm, \>=30 bpm increase from baseline, \>=30 bpm decrease from baseline. SBP: \>140 millimeters of mercury (mmHg) and increase from baseline \>20 mmHg, \>180 mmHg, \<90 mmHg and decrease from baseline \>10 mmHg. DBP: \>90 mmHg and increase from baseline \>20 mmHg, \>105 mmHg, \<60 mmHg and decrease from baseline \>10 mmHg. Change in weight: \>=5% increase from baseline, \>=5% decrease from baseline.

Outcome measures

Outcome measures
Measure	PAG: PEGPH20 + Nab-Paclitaxel + Gemcitabine n=325 Participants Participants received 3.0 μg/kg PEGPH20 as an IV infusion, twice weekly for Weeks 1 to 3 of Cycle 1 (each cycle consisted of 4 weeks \[Week 4 of every cycle was a rest week with no treatment\]), then once weekly for Weeks 1 to 3 of Cycle 2 and beyond in combination with 125 mg/m\^2 nab-paclitaxel as an IV infusion and 1000 mg/m\^2 gemcitabine as an IV infusion, once weekly for Weeks 1 to 3 of all treatment cycles. Treatment was continued until disease progression, unacceptable toxicity, death, or withdrawal of consent (Maximum exposure: 150.1 weeks).	AG: Placebo + Nab-Paclitaxel + Gemcitabine n=156 Participants Participants received placebo matching to PEGPH20 as an IV infusion, twice weekly for Weeks 1 to 3 of Cycle 1 (each cycle consisting of 4 weeks \[Week 4 of every cycle will be a rest week with no treatment\]), then once weekly for Weeks 1 to 3 of Cycle 2 and beyond in combination with 125 mg/m\^2 nab-paclitaxel as an IV infusion and 1000 mg/m\^2 gemcitabine as an IV infusion, once weekly for Weeks 1 to 3 of all treatment cycles. Treatment was continued until disease progression, unacceptable toxicity, death, or withdrawal of consent (Maximum exposure: 83.9 weeks).
Number of Participants With Clinically Significant Abnormalities in Vital Signs Change in weight: >=5% decrease from baseline	151 Participants	57 Participants
Number of Participants With Clinically Significant Abnormalities in Vital Signs Heart rate: <50 bpm	7 Participants	4 Participants
Number of Participants With Clinically Significant Abnormalities in Vital Signs Heart rate: >120 bpm	47 Participants	13 Participants
Number of Participants With Clinically Significant Abnormalities in Vital Signs Heart rate: >=30 bpm increase from baseline	102 Participants	26 Participants
Number of Participants With Clinically Significant Abnormalities in Vital Signs Heart rate: >=30 bpm decrease from baseline	38 Participants	19 Participants
Number of Participants With Clinically Significant Abnormalities in Vital Signs SBP: >140 mmHg and increase from baseline >20 mmHg	75 Participants	37 Participants
Number of Participants With Clinically Significant Abnormalities in Vital Signs SBP: >180 mmHg	6 Participants	4 Participants
Number of Participants With Clinically Significant Abnormalities in Vital Signs SBP: <90 mmHg and decrease from baseline >10 mmHg	60 Participants	17 Participants
Number of Participants With Clinically Significant Abnormalities in Vital Signs DBP: >90 mmHg and increase from baseline >20 mmHg	21 Participants	10 Participants
Number of Participants With Clinically Significant Abnormalities in Vital Signs DBP: >105 mmHg	8 Participants	6 Participants
Number of Participants With Clinically Significant Abnormalities in Vital Signs DBP: <60 mmHg and decrease from baseline >10 mmHg	142 Participants	56 Participants
Number of Participants With Clinically Significant Abnormalities in Vital Signs Change in weight: >=5% increase from baseline	85 Participants	52 Participants

Adverse Events

PAG: PEGPH20 + Nab-Paclitaxel + Gemcitabine

Serious events: 187 serious events

Other events: 198 other events

Deaths: 222 deaths

AG: Placebo + Nab-Paclitaxel + Gemcitabine

Serious events: 80 serious events

Other events: 73 other events

Deaths: 106 deaths

Serious adverse events

Other adverse events

Additional Information

VP, Medical, Regulatory and Drug Safety

Halozyme Therapeutics

Phone: 858-794-8889

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60