A Study of V934/V935 Vaccine in Cancer Participants With Selected Solid Tumors (V934-002)

• Sponsor: Merck Sharp & Dohme LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00753415
• Collaborator: (none)
• Enrollment: 37
• Arms: 10
• Duration (Months): 32

Study Details

Study Description

Brief Summary

This is a two-part study to test the safety, tolerability, and immune response for V934/V935 vaccine using a new prime-boost regimen in participants with selected solid tumors.

Condition or Disease	Intervention/Treatment	Phase
Non-Small Cell Lung Carcinoma; Breast Cancer; Melanoma; Upper GI Tract Carcinoma; Colon Carcinoma; Renal Cell Carcinoma; Bladder Carcinoma; Prostate Cancer	Biological: V935; Biological: V934-EP	Phase 1

Detailed Description

Two vaccines will be administered: V934-electroporation (EP) either low dose (LD) or high dose (HD), and V935 either LD or HD. In Part A, participants will be assigned to V935 vaccine alone or in combination with V934-EP. Part B will be an optional part of the study, offering V934-EP vaccine booster to participants who were enrolled in Part A.

Study Design

• Study Type: Interventional
• Actual Enrollment: 37 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I Investigation of the Safety, Tolerability and Immunogenicity of V934/V935 hTERT Vaccination in Cancer Patients With Selected Solid Tumors
• Study Start Date: Aug 1, 2008
• Actual Primary Completion Date: Apr 1, 2011
• Actual Study Completion Date: Apr 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part A: V935 LD Two intramuscular (IM) injections of V935 low dose (LD), 1 given every other week over a 3-week period.	Biological: V935; A 0.5 mL vaccine administered IM every 2 weeks as either a LD (1 x 10^9 vector genomes/mL) or a HD (1 x 10^11 vector genomes/mL).
Experimental: Part A: V934 LD(3)+V935 LD Three electroporation (EP) injections of V934 (LD) , 1 given every other week over a 5-week period. Following a 4-week observation period, 2 IM injections of V935 (LD) will be administered, 1 given every other week over a 3-week period.	Biological: V935; A 0.5 mL vaccine administered IM every 2 weeks as either a LD (1 x 10^9 vector genomes/mL) or a HD (1 x 10^11 vector genomes/mL).; Biological: V934-EP; A 0.5 mL vaccine administered by EP as either a LD (0.5 mg plasmid/mL) or a HD (5.0 mg plasmid/mL).
Experimental: Part A: V935 HD Two IM injections of V935 high dose (HD), 1 given very other week over a 3-week period.	Biological: V935; A 0.5 mL vaccine administered IM every 2 weeks as either a LD (1 x 10^9 vector genomes/mL) or a HD (1 x 10^11 vector genomes/mL).
Experimental: Part A: V934 HD(3)+V935 HD Three EP injections of V934 (HD), 1 given every other week over a 5-week period. Following a 4-week observation period, 2 IM injections of V935 (HD) will be administered, 1 given every other week over a 3-week period.	Biological: V935; A 0.5 mL vaccine administered IM every 2 weeks as either a LD (1 x 10^9 vector genomes/mL) or a HD (1 x 10^11 vector genomes/mL).; Biological: V934-EP; A 0.5 mL vaccine administered by EP as either a LD (0.5 mg plasmid/mL) or a HD (5.0 mg plasmid/mL).
Experimental: Part A: V934 HD(5)+V935 HD Five EP injections of V934 (HD), 1 given every other week over a 9-week period. Following a 4-week observation period, 2 IM injections of V935 (HD) will be administered, 1 given every other week over a 3-week period.	Biological: V935; A 0.5 mL vaccine administered IM every 2 weeks as either a LD (1 x 10^9 vector genomes/mL) or a HD (1 x 10^11 vector genomes/mL).; Biological: V934-EP; A 0.5 mL vaccine administered by EP as either a LD (0.5 mg plasmid/mL) or a HD (5.0 mg plasmid/mL).
Experimental: Part B: V935 LD/V934 Booster Participants who completed Part A could enter Part B. Following a 12-week observation period, 3 EP injections of V934 booster were administered, 1 given every 2 weeks.	Biological: V934-EP; A 0.5 mL vaccine administered by EP as either a LD (0.5 mg plasmid/mL) or a HD (5.0 mg plasmid/mL).
Experimental: Part B: V934 LD(3)+V935 LD/V934 Booster Participants who complete Part A can enter Part B. Following a 12-week observation period, 3 EP injections of V934 booster will be administered, 1 given every 2 weeks.	Biological: V934-EP; A 0.5 mL vaccine administered by EP as either a LD (0.5 mg plasmid/mL) or a HD (5.0 mg plasmid/mL).
Experimental: Part B: V935 HD/V934 Booster Participants who complete Part A can enter Part B. Following a 12-week observation period, 3 EP injections of V934 booster will be administered, 1 given every 2 weeks.	Biological: V934-EP; A 0.5 mL vaccine administered by EP as either a LD (0.5 mg plasmid/mL) or a HD (5.0 mg plasmid/mL).
Experimental: Part B: V934 HD(3)+V935 HD/V934 Booster Participants who complete Part A can enter Part B. Following a 12-week observation period, 3 EP injections of V934 booster will be administered, 1 given every 2 weeks.	Biological: V934-EP; A 0.5 mL vaccine administered by EP as either a LD (0.5 mg plasmid/mL) or a HD (5.0 mg plasmid/mL).
Experimental: Part B: V934 HD(5)+V935 HD/V934 Booster Participants who complete Part A can enter Part B. Following a 12-week observation period, 3 EP injections of V934 booster will be administered, 1 given every 2 weeks.	Biological: V934-EP; A 0.5 mL vaccine administered by EP as either a LD (0.5 mg plasmid/mL) or a HD (5.0 mg plasmid/mL).

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Dose-Limiting Toxicity (DLT) [Day 1 up to 30 days following the last vaccination (up to 77 weeks); Treatment Period + Acute Follow-up (FU) Period]

   DLT was defined as a vaccine- or EP-related adverse event (AE) including the following: Hematological (Grade 3 neutropenia with fever, Grade 4 neutropenia ≥5 days, Grade 4 thrombocytopenia) or non-hematological AE, Grade 3, 4 or 5 with the exception of Grade 3 nausea, vomiting, diarrhea or serum glutamic oxaloacetic transaminase (SGOT) elevation, alopecia, Grade 3/4 creatinine phosphokinase (CPK) elevation or inadequately treated hypersensitivity. Any Grade 3/4 related AE that failed to return to ≤Grade 1 or baseline within 14 days was also considered a DLT.

2. Number of Participants With Adverse Events (AEs) [Day 1 up to 30 days following the last vaccination (up to 77 weeks); Treatment Period + Acute Follow-up (FU) Period]

   This analysis includes the number of participants with AEs and serious AEs (SAEs) during the Treatment Period plus the Acute Follow-up (FU) Period (up to 30 days following last vaccination). An AE was defined as any unfavorable or unintended change in the structure, function or chemistry of the body temporally associated with the use of the product, whether or not considered related to the product, including any worsening of a preexisting condition which was temporally associated with the product. An SAE was defined as an AE resulting in death, was life-threatening, resulted in or prolonged hospitalization, was a congenital anomaly, a cancer, an overdose or other important medical event.

Secondary Outcome Measures

1. Number of Participants With Immunologic Response to V934/V935 (Immunologic Response Rate) [From pre-vaccination to Week 69]

   An Enzyme-Linked Immunosorbent Spot (ELISPOT) assay was planned to be used to demonstrate a cell mediated immune response to V935 and/or V934 in vaccinated participants. Collection of Peripheral Blood Mononuclear Cells (PBMCs) and serum took place at baseline (Screening and pre-vaccination Day 1), and various time points post vaccination across the three distinct regimens to be tested. A positive immune response was to be defined by a minimum number of spot-forming cells per million PBMC (SFC/10^6 PBMCs) for the antigen well and a minimum n-fold increase in the antigen well over the control well.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria Part A

• Participant has one of the selected solid tumors with no distant metastases, and is more than 8 weeks from completion of definitive therapy with intention to cure. Selected Solid Tumors: Stage I to III non-small cell lung carcinoma (NSCLC); Stage III breast cancer; Stage IIB or III melanoma; Stage II or III upper gastrointestinal tract carcinoma (e.g., esophagus, stomach, gallbladder, pancreas); Stage III colon carcinoma; Stage II, III, or IV (M0 only) renal cell carcinoma; Stage II, III, or IV (M0 only) bladder carcinoma; clinically-localized prostate carcinoma

• Participant has adequate organ function.

• Female participant of childbearing potential has a negative serum pregnancy test within 3 days of study enrollment.

Exclusion Criteria Part A

• Participant has known hypersensitivity to any component of study vaccine.

• Participant has a history of clinically significant cardiac conditions, including cardiac arrhythmias which have not been controlled within the last 3 months, unstable angina, myocardial infarction (within the last 3 months), or New York Heart Association (NYHA) Class III or IV congestive heart failure. Participant must have no clinically significant electrocardiogram (ECG) abnormalities and not have a pacemaker or cardioverter/defibrillator implanted.

• Participant has undergone splenectomy or has any history of autoimmune disorder.

• Participant has received immunosuppressive treatment within 1 month prior to enrollment.

• Participant has known acquired, inherited, or idiopathic thrombocytopenia, platelet dysfunction or coagulopathy that would contraindicate IM injections.

• Participant has an acute infection requiring intravenous antibiotic, antiviral or antifungal agents within 2 weeks of study entry.

• Participant is pregnant or breastfeeding, or expecting to conceive at any time during the study or within 1 year after receiving the last vaccination.

• Participant is known to be Human Immunodeficiency Virus (HIV)-seropositive.

• Participant has known history of Hepatitis B or C or active Hepatitis A.

• Participant has been vaccinated for any disease or for prophylaxis within 1 month prior to the first vaccination.

• The participant has been diagnosed with Systemic Lupus Erythematosus (SLE)

Inclusion Criteria Part B

• Participant must have completed their respective vaccination Treatment Group regimen for Part A of this study.

• Participant must have completed a ≥12 week safety observation period prior to receiving their first V934-EP boost.

Exclusion Criteria Part B

• Participant has new or metastatic tumor lesions since enrollment in Part A.

• Participant has developed any significant cardiac conditions since enrollment in Part A including cardiac arrhythmias which have not been controlled within the last 3 months, unstable angina, myocardial infarction (within the last 3 months), or NYHA Class III or IV congestive heart failure.

• Participant has undergone a splenectomy, or has developed any autoimmune disorders, since enrollment in Part A.

• Participant has received immunosuppressive treatment within 1 month prior to enrollment in Part B

• Participant has developed any acquired, inherited, or idiopathic thrombocytopenia, platelet dysfunction or coagulopathy that would contraindicate IM injections

• Participant has an acute infection requiring intravenous antibiotic, antiviral or antifungal agents within 2 weeks of entry to Part B.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Merck Sharp & Dohme LLC

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Merck Sharp & Dohme LLC
• ClinicalTrials.gov Identifier: NCT00753415
• Other Study ID Numbers: V934-002; 2008_541
• First Posted: Sep 16, 2008
• Last Update Posted: Mar 17, 2015
• Last Verified: Feb 1, 2015

• Keywords provided by Merck Sharp & Dohme LLC: Urinary Bladder Neoplasms; Breast Neoplasms; Renal Cell carcinoma; Melanoma; Prostatic Neoplasms; Colonic Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Urinary Bladder Diseases; Urologic Diseases; Breast Diseases; Skin Diseases; Neoplasms; Glandular and Epithelial Neoplasms by Histologic Type; Adenocarcinoma; Kidney Neoplasms; Kidney Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Genital Neoplasms; Male Genital Diseases; Male, Prostatic Diseases; Colorectal Neoplasms; Intestinal Neoplasms
• Additional relevant MeSH terms: Carcinoma; Melanoma; Carcinoma, Renal Cell; Carcinoma, Non-Small-Cell Lung; Urinary Bladder Neoplasms

Study Results

Participant Flow

Recruitment Details	V935 alone or in combination with V934 was administered to 37 participants with selected solid tumors in Part A.
Pre-assignment Detail	Of the 37 participants who were enrolled in Part A, 32 participants completed and were eligible to enroll in the optional extension study Part B. There were 28 participants who elected to enroll in Part B.

Arm/Group Title	Part A: V935 LD	Part A: V934 LD(3)+V935 LD	Part A: V935 HD	Part A: V934 HD(3)+V935 HD	Part A: V934 HD(5)+V935 HD	Part B: V935 LD/V934 Booster	Part B: V934 LD(3)+V935 LD/V934 Booster	Part B: V935 HD/V934 Booster	Part B: V934 HD(3)+V935 HD/V934 Booster	Part B: V934 HD(5)+V934 HD/V934 Booster
Arm/Group Description	Two intramuscular (IM) injections of V935 low dose (LD), 1 given every other week over a 3-week period.	Three electroporation (EP) injections of V934 (LD) were administered, 1 given every other week over a 5-week period. Following a 4-week observation period, 2 IM injections of V935 (LD) were administered, 1 given every other week over a 3-week period.	Two IM injections of V935 high dose (HD), 1 given every other week over a 3-week period.	Three EP injections of V934 (HD) were administered, 1 given every other week over a 5-week period. Following a 4-week observation period, 2 IM injections of V935 (HD) were administered, 1 given every other week over a 3-week period.	Five EP injections of V934 (HD) were administered, 1 given every other week over a 9-week period. Following a 4-week observation period, 2 IM injections of V935 (HD) were administered, 1 given every other week over a 3-week period.	Participants who completed Part A could enter Part B. Following a 12-week observation period, 3 EP injections of V934-EP booster were administered, 1 given every 2 weeks.	Participants who completed Part A could enter Part B. Following a 12-week observation period, 3 EP injections of V934 booster were administered, 1 given every 2 weeks.	Participants who completed Part A could enter Part B. Following a 12-week observation period, 3 EP injections of V934 booster were administered, 1 given every 2 weeks.	Participants who completed Part A could enter Part B. Following a 12-week observation period, 3 EP injections of V934 booster were administered, 1 given every 2 weeks.	Participants who completed Part A could enter Part B. Following a 12-week observation period, 3 EP injections of V934 booster were administered, 1 given every 2 weeks.
Period Title: Part A
STARTED	3	3	10	11	10	0	0	0	0	0
COMPLETED	2	3	8	9	10	0	0	0	0	0
NOT COMPLETED	1	0	2	2	0	0	0	0	0	0
Period Title: Part A
STARTED	0	0	0	0	0	1	2	7	9	9
COMPLETED	0	0	0	0	0	1	2	6	6	8
NOT COMPLETED	0	0	0	0	0	0	0	1	3	1

Baseline Characteristics

Arm/Group Title	Part A: V935 LD	Part A: V934 LD(3)+V935 LD	Part A: V935 HD	Part A: V934 HD(3)+V935 HD	Part A: V934 HD(5)+V935 HD	Total
Arm/Group Description	Two IM injections of V935 low dose (LD), 1 given every other week over a 3-week period.	Three electroporation (EP) injections of V934 (LD) were administered, 1 given every other week over a 5-week period. Following a 4 week observation period, 2 IM injections of V935 (LD) were administered, 1 given every other week over a 3-week period.	Two IM injections of V935 high dose (HD), 1 given very other week over a 3-week period.	Three EP injections of V934 (HD) were administered, 1 given every other week over a 5-week period. Following a 4 week observation period, 2 IM injections of V935 (HD) were administered, 1 given every other week over a 3-week period.	Five EP injections of V934 (HD) were administered, 1 given every other week over a 9-week period. Following a 4-week observation period, 2 IM injections of V935 (HD) were administered, 1 given every other week over a 3-week period.	Total of all reporting groups
Overall Participants	3	3	10	11	10	37
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	70.0 (9.5)	70.0 (6.2)	63.8 (10.0)	58.8 (11.7)	60.2 (11.7)	62.4 (11.0)
Sex: Female, Male (Count of Participants)
Female	0 0%	1 33.3%	4 40%	4 36.4%	1 10%	10 27%
Male	3 100%	2 66.7%	6 60%	7 63.6%	9 90%	27 73%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Dose-Limiting Toxicity (DLT)
Description	DLT was defined as a vaccine- or EP-related adverse event (AE) including the following: Hematological (Grade 3 neutropenia with fever, Grade 4 neutropenia ≥5 days, Grade 4 thrombocytopenia) or non-hematological AE, Grade 3, 4 or 5 with the exception of Grade 3 nausea, vomiting, diarrhea or serum glutamic oxaloacetic transaminase (SGOT) elevation, alopecia, Grade 3/4 creatinine phosphokinase (CPK) elevation or inadequately treated hypersensitivity. Any Grade 3/4 related AE that failed to return to ≤Grade 1 or baseline within 14 days was also considered a DLT.
Time Frame	Day 1 up to 30 days following the last vaccination (up to 77 weeks); Treatment Period + Acute Follow-up (FU) Period

Outcome Measure Data

Analysis Population Description

Evaluable patients who completed all scheduled vaccinations were included in the DLT analysis.

Arm/Group Title	Part A: V935 LD	Part A: V934 LD(3)+V935 LD	Part A: V935 HD	Part A: V934 HD(3)+V935 HD	Part A: V934 HD(5)+V935 HD	Part B: V935 LD/V934 Booster	Part B: V934 LD(3)+V935 LD/V934 Booster	Part B: V935 HD/V934 Booster	Part B: V934 HD(3)+V935 HD/V934 Booster	Part B: V934 HD(5)+V935 HD/V934 Booster
Arm/Group Description	Two IM injections of V935 low dose (LD), 1 given every other week over a 3-week period.	Three electroporation (EP) injections of V934 (LD) were administered, 1 given every other week over a 5-week period. Following a 4 week observation period, 2 IM injections of V935 (LD) were administered, 1 given every other week over a 3-week period.	Two IM injections of V935 high dose (HD), 1 given very other week over a 3-week period.	Three EP injections of V934 (HD) were administered, 1 given every other week over a 5-week period. Following a 4 week observation period, 2 IM injections of V935 (HD) were administered, 1 given every other week over a 3-week period.	Five EP injections of V934 (HD) were administered, 1 given every other week over a 9-week period. Following a 4-week observation period, 2 IM injections of V935 (HD) were administered, 1 given every other week over a 3-week period.	Participants who completed Part A could enter Part B. Following a 12-week observation period, 3 EP injections of V934 booster were administered, 1 given every 2 weeks.	Participants who completed Part A could enter Part B. Following a 12-week observation period, 3 EP injections of V934 booster were administered, 1 given every 2 weeks.	Participants who completed Part A could enter Part B. Following a 12-week observation period, 3 EP injections of V934 booster were administered, 1 given every 2 weeks.	Participants who completed Part A could enter Part B. Following a 12-week observation period, 3 EP injections of V934 booster were administered, 1 given every 2 weeks.	Participants who completed Part A could enter Part B. Following a 12-week observation period, 3 EP injections of V934 booster were administered, 1 given every 2 weeks.
Measure Participants	3	3	10	11	10	1	2	7	9	9
Number [Participants]	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 NaN	0 NaN	0 NaN	0 NaN

2. Primary Outcome

Title	Number of Participants With Adverse Events (AEs)
Description	This analysis includes the number of participants with AEs and serious AEs (SAEs) during the Treatment Period plus the Acute Follow-up (FU) Period (up to 30 days following last vaccination). An AE was defined as any unfavorable or unintended change in the structure, function or chemistry of the body temporally associated with the use of the product, whether or not considered related to the product, including any worsening of a preexisting condition which was temporally associated with the product. An SAE was defined as an AE resulting in death, was life-threatening, resulted in or prolonged hospitalization, was a congenital anomaly, a cancer, an overdose or other important medical event.
Time Frame	Day 1 up to 30 days following the last vaccination (up to 77 weeks); Treatment Period + Acute Follow-up (FU) Period

Outcome Measure Data

Analysis Population Description

All Participants as Treated (APaT) population; all participants who received at least one vaccination.

Arm/Group Title	Part A: V935 LD	Part A: V934 LD(3)+V935 LD	Part A: V935 HD	Part A: V934 HD(3)+V935 HD	Part A: V934 HD(5)+V935 HD	Part B: V935 LD/V934 Booster	Part B: V934 LD(3)+V935 LD/V934 Booster	Part B: V935 HD/V934 Booster	Part B: V934 HD(3)+V935 HD/V934 Booster	Part B: V934 HD(5)+V935 HD/V934 Booster
Arm/Group Description	Two IM injections of V935 low dose (LD), 1 given every other week over a 3-week period.	Three electroporation (EP) injections of V934 (LD) were administered, 1 given every other week over a 5-week period. Following a 4 week observation period, 2 IM injections of V935 (LD) were administered, 1 given every other week over a 3-week period.	Two IM injections of V935 high dose (HD), 1 given very other week over a 3-week period.	Three EP injections of V934 (HD) were administered, 1 given every other week over a 5-week period. Following a 4 week observation period, 2 IM injections of V935 (HD) were administered, 1 given every other week over a 3-week period.	Five EP injections of V934 (HD) were administered, 1 given every other week over a 9-week period. Following a 4-week observation period, 2 IM injections of V935 (HD) were administered, 1 given every other week over a 3-week period.	Participants who completed Part A could enter Part B. Following a 12-week observation period, 3 EP injections of V934 booster were administered, 1 given every 2 weeks.	Participants who completed Part A could enter Part B. Following a 12-week observation period, 3 EP injections of V934 booster were administered, 1 given every 2 weeks.	Participants who completed Part A could enter Part B. Following a 12-week observation period, 3 EP injections of V934 booster were administered, 1 given every 2 weeks.	Participants who completed Part A could enter Part B. Following a 12-week observation period, 3 EP injections of V934 booster were administered, 1 given every 2 weeks.	Participants who completed Part A could enter Part B. Following a 12-week observation period, 3 EP injections of V934 booster were administered, 1 given every 2 weeks.
Measure Participants	3	3	10	11	10	1	2	7	9	9
Number [Participants]	3 100%	3 100%	8 80%	11 100%	10 100%	1 2.7%	1 NaN	3 NaN	8 NaN	7 NaN

3. Secondary Outcome

Title	Number of Participants With Immunologic Response to V934/V935 (Immunologic Response Rate)
Description	An Enzyme-Linked Immunosorbent Spot (ELISPOT) assay was planned to be used to demonstrate a cell mediated immune response to V935 and/or V934 in vaccinated participants. Collection of Peripheral Blood Mononuclear Cells (PBMCs) and serum took place at baseline (Screening and pre-vaccination Day 1), and various time points post vaccination across the three distinct regimens to be tested. A positive immune response was to be defined by a minimum number of spot-forming cells per million PBMC (SFC/10^6 PBMCs) for the antigen well and a minimum n-fold increase in the antigen well over the control well.
Time Frame	From pre-vaccination to Week 69

Outcome Measure Data

Analysis Population Description

Planned analysis for the secondary endpoint of Immunologic Response Rate was not performed due to study de-prioritization.

Arm/Group Title	Part A: V935 LD	Part A: V934 LD(3)+V935 LD	Part A: V935 HD	Part A: V934 HD(3)+V935 HD	Part A: V934 HD(5)+V935 HD	Part B: V935 LD/V934 Booster	Part B: V934 LD(3)+V935 LD/V934 Booster	Part B: V935 HD/V934 Booster	Part B: V934 HD(3)+V935 HD/V934 Booster	Part B: V934 HD(5)+V935 HD/V934 Booster
Arm/Group Description	Two IM injections of V935 low dose (LD), 1 given every other week over a 3-week period.	Three electroporation (EP) injections of V934 (LD) were administered, 1 given every other week over a 5-week period. Following a 4 week observation period, 2 IM injections of V935 (LD) were administered, 1 given every other week over a 3-week period.	Two IM injections of V935 high dose (HD), 1 given very other week over a 3-week period.	Three EP injections of V934 (HD) were administered, 1 given every other week over a 5-week period. Following a 4 week observation period, 2 IM injections of V935 (HD) were administered, 1 given every other week over a 3-week period.	Five EP injections of V934 (HD) were administered, 1 given every other week over a 9-week period. Following a 4-week observation period, 2 IM injections of V935 (HD) were administered, 1 given every other week over a 3-week period.	Participants who completed Part A could enter Part B. Following a 12-week observation, 3 EP injections of V934 booster were administered, 1 given every 2 weeks.	Participants who completed Part A could enter Part B. Following a 12-week observation period, 3 EP injections of V934 booster were administered, 1 given every 2 weeks.	Participants who completed Part A could enter Part B. Following a 12-week observation period, V934-EP booster was administered, 1 given every 2 weeks for 3 doses.	Participants who completed Part A could enter Part B. Following a 12-week observation period, 3 EP injections of V934 booster were administered, 1 given every 2 weeks.	Participants who completed Part A could enter Part B. Following a 12-week observation period, 3 EP injections of V934 booster were administered, 1 given every 2 weeks.
Measure Participants	0	0	0	0	0	0	0	0	0	0

Adverse Events

Time Frame	SAEs reported for Treatment Period+Acute FU+Chronic FU;Part A: Day 1 up to Wk 69, Part B: Day 1 up to 6 months post last vaccination-Wk 28). Nonserious AEs (Parts A&B) reported for Treatment Period+Acute FU;Day 1 up to 30 days post last vaccination-77 Wks
Adverse Event Reporting Description	Participants who completed Part A had the option to enter Part B.
Arm/Group Title	Part A: V935 LD		Part A: V934 LD(3)+V935 LD		Part A: V935 HD		Part A: V934 HD(3)+V935 HD		Part A: V934 HD(5)+V935 HD		Part B: V935 LD/V934 Booster		Part B: V934 LD(3)+V935 LD/V934 Booster		Part B: V935 HD/V934 Booster		Part B: V934 HD(3)+V935 HD/V934 Booster		Part B: V934 HD(5)+V935 HD/V934 Booster
Arm/Group Description	Two IM injections of V935 low dose (LD), 1 given every other week over a 3-week period.		Three electroporation (EP) injections of V934 (LD) were administered, 1 given every other week over a 5-week period. Following a 4 week observation period, 2 IM injections of V935 (LD) were administered, 1 given every other week over a 3-week period.		Two IM injections of V935 high dose (HD), 1 given very other week over a 3-week period.		Three EP injections of V934 (HD) were administered, 1 given every other week over a 5-week period. Following a 4 week observation period, 2 IM injections of V935 (HD) were administered, 1 given every other week over a 3-week period.		Five EP injections of V934 (HD) were administered, 1 given every other week over a 9-week period. Following a 4-week observation period, 2 IM injections of V935 (HD) were administered, 1 given every other week over a 3-week period.		Participants who completed Part A could enter Part B. Following a 12-week observation, 3 EP injections of V934 booster were administered, 1 given every 2 weeks.		Participants who completed Part A could enter Part B. Following a 12-week observation period, 3 EP injections of V934 booster were administered, 1 given every 2 weeks.		Participants who completed Part A could enter Part B. Following a 12-week observation period, 3 EP injections of V934 booster were administered, 1 given every 2 weeks.		Participants who completed Part A could enter Part B. Following a 12-week observation period, 3 EP injections of V934 booster were administered, 1 given every 2 weeks.		Participants who completed Part A could enter Part B. Following a 12-week observation period, 3 EP injections of V934 booster were administered, 1 given every 2 weeks.
All Cause Mortality
	Part A: V935 LD		Part A: V934 LD(3)+V935 LD		Part A: V935 HD		Part A: V934 HD(3)+V935 HD		Part A: V934 HD(5)+V935 HD		Part B: V935 LD/V934 Booster		Part B: V934 LD(3)+V935 LD/V934 Booster		Part B: V935 HD/V934 Booster		Part B: V934 HD(3)+V935 HD/V934 Booster		Part B: V934 HD(5)+V935 HD/V934 Booster
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Part A: V935 LD		Part A: V934 LD(3)+V935 LD		Part A: V935 HD		Part A: V934 HD(3)+V935 HD		Part A: V934 HD(5)+V935 HD		Part B: V935 LD/V934 Booster		Part B: V934 LD(3)+V935 LD/V934 Booster		Part B: V935 HD/V934 Booster		Part B: V934 HD(3)+V935 HD/V934 Booster		Part B: V934 HD(5)+V935 HD/V934 Booster
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/3 (33.3%)		0/3 (0%)		2/10 (20%)		2/11 (18.2%)		1/10 (10%)		0/1 (0%)		0/2 (0%)		0/7 (0%)		0/9 (0%)		0/9 (0%)
Cardiac disorders
Pericardial effusion	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	0/10 (0%)	0	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Coronary artery stenosis	1/3 (33.3%)	1	0/3 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	0/10 (0%)	0	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Gastrointestinal disorders
Upper gastrointestinal haemorrhage	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	0/10 (0%)	0	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Infections and infestations
Cellulitis	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/10 (10%)	1	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Lobar pneumonia	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	0/10 (0%)	0	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Pneumonia	1/3 (33.3%)	1	0/3 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	0/10 (0%)	0	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Investigations
Haematocrit decreased	0/3 (0%)	0	0/3 (0%)	0	1/10 (10%)	1	0/11 (0%)	0	0/10 (0%)	0	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder cancer	0/3 (0%)	0	0/3 (0%)	0	1/10 (10%)	1	0/11 (0%)	0	0/10 (0%)	0	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Psychiatric disorders
Depressed mood	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/10 (10%)	1	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Other (Not Including Serious) Adverse Events
	Part A: V935 LD		Part A: V934 LD(3)+V935 LD		Part A: V935 HD		Part A: V934 HD(3)+V935 HD		Part A: V934 HD(5)+V935 HD		Part B: V935 LD/V934 Booster		Part B: V934 LD(3)+V935 LD/V934 Booster		Part B: V935 HD/V934 Booster		Part B: V934 HD(3)+V935 HD/V934 Booster		Part B: V934 HD(5)+V935 HD/V934 Booster
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/3 (100%)		3/3 (100%)		8/10 (80%)		11/11 (100%)		10/10 (100%)		1/1 (100%)		1/2 (50%)		3/7 (42.9%)		8/9 (88.9%)		7/9 (77.8%)
Blood and lymphatic system disorders
Anaemia	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	1/10 (10%)	1	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Lymphopenia	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	2	1/10 (10%)	4	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	1/9 (11.1%)	2	1/9 (11.1%)	1
Neutropenia	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/10 (10%)	1	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Cardiac disorders
Atrial fibrillation	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	0/10 (0%)	0	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Tachycardia	0/3 (0%)	0	0/3 (0%)	0	1/10 (10%)	1	0/11 (0%)	0	0/10 (0%)	0	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Ear and labyrinth disorders
Vertigo	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	0/10 (0%)	0	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Eye disorders
Conjunctival haemorrhage	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	0/10 (0%)	0	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Eye irritation	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/10 (10%)	1	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Ocular hyperaemia	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	0/10 (0%)	0	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Gastrointestinal disorders
Abdominal distension	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	0/10 (0%)	0	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Abdominal pain	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	0/10 (0%)	0	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	1/9 (11.1%)	1
Constipation	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	2/11 (18.2%)	2	0/10 (0%)	0	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Diarrhoea	0/3 (0%)	0	0/3 (0%)	0	1/10 (10%)	1	3/11 (27.3%)	3	1/10 (10%)	1	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Dyspepsia	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/10 (10%)	2	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Food poisoning	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/10 (10%)	1	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Gastritis	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/10 (10%)	1	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Gastrooesophageal reflux disease	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/10 (10%)	1	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Inguinal hernia	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/10 (10%)	1	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Nausea	0/3 (0%)	0	0/3 (0%)	0	2/10 (20%)	2	3/11 (27.3%)	3	2/10 (20%)	2	0/1 (0%)	0	0/2 (0%)	0	1/7 (14.3%)	1	0/9 (0%)	0	0/9 (0%)	0
Vomiting	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	0/10 (0%)	0	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
General disorders
Chest discomfort	0/3 (0%)	0	1/3 (33.3%)	1	0/10 (0%)	0	0/11 (0%)	0	0/10 (0%)	0	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Chills	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/10 (10%)	1	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Fatigue	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	5/11 (45.5%)	11	6/10 (60%)	10	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	2/9 (22.2%)	2	1/9 (11.1%)	2
Feeling hot	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/10 (10%)	4	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Feeling jittery	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	0/10 (0%)	0	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	1/9 (11.1%)	1	0/9 (0%)	0
Influenza like illness	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/10 (10%)	2	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Injection site erythema	0/3 (0%)	0	2/3 (66.7%)	3	0/10 (0%)	0	8/11 (72.7%)	19	6/10 (60%)	17	0/1 (0%)	0	0/2 (0%)	0	1/7 (14.3%)	3	6/9 (66.7%)	11	3/9 (33.3%)	6
Injection site haematoma	0/3 (0%)	0	0/3 (0%)	0	1/10 (10%)	1	0/11 (0%)	0	1/10 (10%)	1	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	1/9 (11.1%)	1	0/9 (0%)	0
Injection site induration	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	0/10 (0%)	0	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Injection site pain	0/3 (0%)	0	1/3 (33.3%)	1	0/10 (0%)	0	8/11 (72.7%)	21	9/10 (90%)	38	1/1 (100%)	1	1/2 (50%)	1	3/7 (42.9%)	7	5/9 (55.6%)	12	7/9 (77.8%)	14
Injection site paraesthesia	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/10 (10%)	1	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Injection site reaction	0/3 (0%)	0	1/3 (33.3%)	1	0/10 (0%)	0	1/11 (9.1%)	1	1/10 (10%)	1	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Injection site scab	0/3 (0%)	0	0/3 (0%)	0	1/10 (10%)	1	0/11 (0%)	0	1/10 (10%)	1	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Injection site scar	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	0/10 (0%)	0	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	1/9 (11.1%)	1	0/9 (0%)	0
Injection site swelling	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	8/11 (72.7%)	13	6/10 (60%)	6	0/1 (0%)	0	0/2 (0%)	0	2/7 (28.6%)	2	4/9 (44.4%)	6	2/9 (22.2%)	2
Nodule	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	0/10 (0%)	0	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Oedema	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/10 (10%)	1	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Oedema peripheral	0/3 (0%)	0	1/3 (33.3%)	1	0/10 (0%)	0	1/11 (9.1%)	1	0/10 (0%)	0	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Pain	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/10 (10%)	1	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Pyrexia	0/3 (0%)	0	0/3 (0%)	0	1/10 (10%)	1	1/11 (9.1%)	3	2/10 (20%)	2	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Injection site mass	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	0/10 (0%)	0	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Hepatobiliary disorders
Hyperbilirubinaemia	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/10 (10%)	1	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Infections and infestations
Bronchitis	0/3 (0%)	0	0/3 (0%)	0	1/10 (10%)	1	0/11 (0%)	0	0/10 (0%)	0	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Celllulitis	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	1/10 (10%)	1	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Ear lobe infection	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	0/10 (0%)	0	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Herpes zoster	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	0/10 (0%)	0	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Influenza	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	0/10 (0%)	0	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Lobar pneumonia	0/3 (0%)	0	0/3 (0%)	0	1/10 (10%)	1	0/11 (0%)	0	0/10 (0%)	0	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Nasopharyngitis	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	4/10 (40%)	5	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Respiratory tract infection viral	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/10 (10%)	1	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Sinusitis	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/10 (10%)	1	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Skin infection	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	0/10 (0%)	0	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Upper respiratory tract infection	0/3 (0%)	0	1/3 (33.3%)	1	0/10 (0%)	0	1/11 (9.1%)	1	1/10 (10%)	1	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	1/9 (11.1%)	1	0/9 (0%)	0
Injury, poisoning and procedural complications
Arthropod sting	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	2/11 (18.2%)	2	0/10 (0%)	0	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Contusion	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	2/11 (18.2%)	2	0/10 (0%)	0	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Mountain sickness acute	0/3 (0%)	0	0/3 (0%)	0	1/10 (10%)	1	0/11 (0%)	0	0/10 (0%)	0	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Investigations
Blood alkaline phosphatase increased	0/3 (0%)	0	0/3 (0%)	0	1/10 (10%)	1	0/11 (0%)	0	0/10 (0%)	0	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Blood amylase increased	0/3 (0%)	0	0/3 (0%)	0	1/10 (10%)	1	1/11 (9.1%)	1	1/10 (10%)	1	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Blood creatinine increased	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	0/10 (0%)	0	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Blood lactic acid increased	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	1/10 (10%)	1	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	1/9 (11.1%)	1	0/9 (0%)	0
Blood magnesium decreased	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/10 (10%)	2	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Blood potassium increased	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/10 (10%)	1	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Blood urine	0/3 (0%)	0	0/3 (0%)	0	1/10 (10%)	1	0/11 (0%)	0	0/10 (0%)	0	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Blood urine present	0/3 (0%)	0	0/3 (0%)	0	1/10 (10%)	1	0/11 (0%)	0	0/10 (0%)	0	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Glomerular filtration rate increased	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	0/10 (0%)	0	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Lipase increased	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	0/10 (0%)	0	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Lymphocyte count decreased	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	2	0/10 (0%)	0	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Platelet count decreased	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/10 (10%)	1	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Protein total increased	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	0/10 (0%)	0	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
White blood cell count decreased	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	2	0/10 (0%)	0	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
White blood cells urine	0/3 (0%)	0	0/3 (0%)	0	1/10 (10%)	1	0/11 (0%)	0	0/10 (0%)	0	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
White blood cells urine positive	0/3 (0%)	0	0/3 (0%)	0	1/10 (10%)	1	0/11 (0%)	0	0/10 (0%)	0	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Metabolism and nutrition disorders
Decreased appetite	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	2/11 (18.2%)	2	1/10 (10%)	1	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Hyperglycaemia	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	0/10 (0%)	0	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Hyponatraemia	0/3 (0%)	0	0/3 (0%)	0	1/10 (10%)	1	0/11 (0%)	0	0/10 (0%)	0	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	0/3 (0%)	0	0/3 (0%)	0	1/10 (10%)	3	1/11 (9.1%)	1	1/10 (10%)	1	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	1/9 (11.1%)	1	0/9 (0%)	0
Back pain	0/3 (0%)	0	0/3 (0%)	0	2/10 (20%)	2	2/11 (18.2%)	2	0/10 (0%)	0	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Flank pain	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	0/10 (0%)	0	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Groin pain	0/3 (0%)	0	0/3 (0%)	0	1/10 (10%)	1	0/11 (0%)	0	0/10 (0%)	0	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Muscular weakness	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	0/10 (0%)	0	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	1/9 (11.1%)	1
Musculoskeletal pain	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	1/10 (10%)	1	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	1/9 (11.1%)	1
Myalgia	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	2/11 (18.2%)	3	0/10 (0%)	0	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	1/9 (11.1%)	1	0/9 (0%)	0
Neck pain	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	2/10 (20%)	2	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	1/9 (11.1%)	1	0/9 (0%)	0
Pain in extremity	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	0/10 (0%)	0	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Soft tissue disorder	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/10 (10%)	1	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Joint swelling	1/3 (33.3%)	1	0/3 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	0/10 (0%)	0	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/10 (10%)	1	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Nervous system disorders
Dizziness	1/3 (33.3%)	1	0/3 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	1/10 (10%)	1	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	1/9 (11.1%)	1
Headache	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	1/10 (10%)	3	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	1/9 (11.1%)	1
Neuralgia	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/10 (10%)	1	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Neuropathy peripheral	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	0/10 (0%)	0	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Paraesthesia	0/3 (0%)	0	1/3 (33.3%)	1	0/10 (0%)	0	0/11 (0%)	0	0/10 (0%)	0	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Peripheral sensory neuropathy	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	0/10 (0%)	0	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Peroneal nerve palsy	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	0/10 (0%)	0	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	1/9 (11.1%)	1
Presyncope	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/10 (10%)	1	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Psychiatric disorders
Anxiety	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	2/10 (20%)	2	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Insomnia	1/3 (33.3%)	1	0/3 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	0/10 (0%)	0	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Renal and urinary disorders
Haematuria	0/3 (0%)	0	0/3 (0%)	0	1/10 (10%)	1	0/11 (0%)	0	0/10 (0%)	0	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	0/3 (0%)	0	0/3 (0%)	0	1/10 (10%)	1	1/11 (9.1%)	1	2/10 (20%)	2	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Dyspnoea	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	2/11 (18.2%)	2	2/10 (20%)	2	0/1 (0%)	0	0/2 (0%)	0	1/7 (14.3%)	1	0/9 (0%)	0	0/9 (0%)	0
Dyspnoea exertional	0/3 (0%)	0	0/3 (0%)	0	1/10 (10%)	1	0/11 (0%)	0	0/10 (0%)	0	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Nasal congestion	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	0/10 (0%)	0	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Oropharyngeal pain	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	3	1/10 (10%)	1	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Productive cough	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/10 (10%)	2	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Pulmonary embolism	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/10 (10%)	1	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Rhinorrhoea	1/3 (33.3%)	1	0/3 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	0/10 (0%)	0	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	1/9 (11.1%)	1	0/9 (0%)	0
Sinus congestion	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	0/10 (0%)	0	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	1/9 (11.1%)	1
Upper respiratory tract congestion	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/10 (10%)	1	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Aspiration	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/10 (10%)	1	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Skin and subcutaneous tissue disorders
Acne	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	0/10 (0%)	0	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Alopecia	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	0/10 (0%)	0	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Erythema	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/10 (10%)	2	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Hirsutism	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	0/10 (0%)	0	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Hyperhidrosis	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/10 (10%)	1	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Onychoclasis	0/3 (0%)	0	1/3 (33.3%)	1	0/10 (0%)	0	0/11 (0%)	0	0/10 (0%)	0	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Rash	0/3 (0%)	0	1/3 (33.3%)	1	0/10 (0%)	0	0/11 (0%)	0	0/10 (0%)	0	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	2/9 (22.2%)	2
Rash erythematous	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	0/10 (0%)	0	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Pruritus	1/3 (33.3%)	1	0/3 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	0/10 (0%)	0	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Vascular disorders
Hot flush	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/10 (10%)	1	0/1 (0%)	0	0/2 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/9 (0%)	0

Limitations/Caveats

[Not Specified]

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Principal Investigators are NOT employed by the organization sponsoring the study.

The SPONSOR must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the SPONSOR as confidential must be deleted prior to submission.