Trial Outcomes & Findings for Safety, Tolerability, and Immunogenicity Study of Investigational Recombinant Botulinum Vaccine A/B (rBV A/B) in Volunteers Previously Immunized With Investigational Pentavalent Botulinum Toxoid (NCT NCT01701999)

NCT ID: NCT01701999

Last Updated: 2017-05-16

Results Overview

Proportion of participants achieving a four-fold or greater increase in NAC up to Week 4 compared with Week 0 for both botulinum toxin A and toxin B (a proportion ≥ 0.50 was considered a success).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

45 participants

Primary outcome timeframe

Week 0 to Week 4

Results posted on

2017-05-16

Participant Flow

Participant milestones

Participant milestones
Measure	Initial Safety and Immunogenicity (Part 1) Part 1 included scheduled assessments of the safety and immunogenicity of a single 40 µg dose of rBV A/B over a 12-week period with a safety follow-up at 6 months.	Safety, Immunogenicity, and Plasma Collection (Part 2) Part 2 was conducted to collect source plasma for potential use in the production of BabyBIG® and to assess safety and immunogenicity of a single 40 µg dose of over a 12-week period; Part 2 included a follow-up for safety assessment at 6 months. Participants in Part 2 did not participate in Part 1.
Overall Study STARTED	8	37
Overall Study COMPLETED	8	37
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Safety, Tolerability, and Immunogenicity Study of Investigational Recombinant Botulinum Vaccine A/B (rBV A/B) in Volunteers Previously Immunized With Investigational Pentavalent Botulinum Toxoid

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Initial Safety and Immunogenicity (Part 1) n=8 Participants Part 1 included scheduled assessments of the safety and immunogenicity of a single 40 µg dose of rBV A/B over a 12-week period with a safety follow-up at 6 months.	Safety, Immunogenicity, and Plasma Collection (Part 2) n=37 Participants Part 2 was conducted to collect source plasma for potential use in the production of BabyBIG® and to assess safety and immunogenicity of a single 40 µg dose of over a 12-week period; Part 2 included a follow-up for safety assessment at 6 months. Participants in Part 2 did not participate in Part 1.	Total n=45 Participants Total of all reporting groups
Age, Continuous	50.3 years STANDARD_DEVIATION 13.5 • n=93 Participants	44.0 years STANDARD_DEVIATION 10.7 • n=4 Participants	45.1 years STANDARD_DEVIATION 11.3 • n=27 Participants
Sex: Female, Male Female	3 Participants n=93 Participants	20 Participants n=4 Participants	23 Participants n=27 Participants
Sex: Female, Male Male	5 Participants n=93 Participants	17 Participants n=4 Participants	22 Participants n=27 Participants

PRIMARY outcome

Timeframe: Week 0 to Week 4

Proportion of participants achieving a four-fold or greater increase in NAC up to Week 4 compared with Week 0 for both botulinum toxin A and toxin B (a proportion ≥ 0.50 was considered a success).

Outcome measures

Outcome measures
Measure	Initial Safety and Immunogenicity (Part 1) n=8 Participants Part 1 included scheduled assessments of the safety and immunogenicity of a single 40 µg dose of rBV A/B over a 12-week period with a safety follow-up at 6 months.	Safety, Immunogenicity, and Plasma Collection (Part 2) n=37 Participants Part 2 was conducted to collect source plasma for potential use in the production of BabyBIG® and to assess safety and immunogenicity of a single 40 µg dose of over a 12-week period; Part 2 included a follow-up for safety assessment at 6 months. Participants in Part 2 did not participate in Part 1.
Four-Fold Increase in Neutralizing Antibody Concentration (NAC) Type A	0.75 proportion of participants	0.84 proportion of participants
Four-Fold Increase in Neutralizing Antibody Concentration (NAC) Type B	0.75 proportion of participants	0.89 proportion of participants

SECONDARY outcome

Timeframe: Week 0 to Week 4

Proportion of participants achieving a three-fold or greater increase in NAC up to Week 4 compared with Week 0 for both botulinum toxin A and toxin B (a proportion ≥ 0.50 was considered a success)

Outcome measures

Outcome measures
Measure	Initial Safety and Immunogenicity (Part 1) n=8 Participants Part 1 included scheduled assessments of the safety and immunogenicity of a single 40 µg dose of rBV A/B over a 12-week period with a safety follow-up at 6 months.	Safety, Immunogenicity, and Plasma Collection (Part 2) n=37 Participants Part 2 was conducted to collect source plasma for potential use in the production of BabyBIG® and to assess safety and immunogenicity of a single 40 µg dose of over a 12-week period; Part 2 included a follow-up for safety assessment at 6 months. Participants in Part 2 did not participate in Part 1.
Three-Fold Increase in Neutralizing Antibody Concentration (NAC) Type A	0.75 proportion of participants	0.95 proportion of participants
Three-Fold Increase in Neutralizing Antibody Concentration (NAC) Type B	0.75 proportion of participants	0.89 proportion of participants

SECONDARY outcome

Timeframe: Week 0 to Week 12

Proportion of participants achieving a two-fold increase in the area under the plasma NAC-time curve between Week 0 and Week 12 in comparison with a straight-line extension of the Week 0 NAC to Week 12 for both botulinum toxin A and toxin B. A proportion ≥ 0.50 was considered a success.

Outcome measures

Outcome measures
Measure	Initial Safety and Immunogenicity (Part 1) n=8 Participants Part 1 included scheduled assessments of the safety and immunogenicity of a single 40 µg dose of rBV A/B over a 12-week period with a safety follow-up at 6 months.	Safety, Immunogenicity, and Plasma Collection (Part 2) n=37 Participants Part 2 was conducted to collect source plasma for potential use in the production of BabyBIG® and to assess safety and immunogenicity of a single 40 µg dose of over a 12-week period; Part 2 included a follow-up for safety assessment at 6 months. Participants in Part 2 did not participate in Part 1.
Two-Fold Increase in the Area Under the Neutralizing Antibody Concentration (NAC) Curve Type A	0.75 proportion of participants	0.95 proportion of participants
Two-Fold Increase in the Area Under the Neutralizing Antibody Concentration (NAC) Curve Type B	0.88 proportion of participants	0.89 proportion of participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 1 to Week 12

Population: Participants in Part 1 were only analyzed for safety data, and one participant in Part 2 was excluded from plasma collection due to not meeting the plasma donor minimum weight requirement.

Measurement of the volume of source plasma containing neutralizing antibodies against botulinum toxin type A and type B collected by plasmapheresis in Part 2.

Outcome measures

Outcome measures
Measure	Initial Safety and Immunogenicity (Part 1) Part 1 included scheduled assessments of the safety and immunogenicity of a single 40 µg dose of rBV A/B over a 12-week period with a safety follow-up at 6 months.	Safety, Immunogenicity, and Plasma Collection (Part 2) n=36 Participants Part 2 was conducted to collect source plasma for potential use in the production of BabyBIG® and to assess safety and immunogenicity of a single 40 µg dose of over a 12-week period; Part 2 included a follow-up for safety assessment at 6 months. Participants in Part 2 did not participate in Part 1.
Collected Plasma Volume	—	13463.3 mL Standard Deviation 4440.5

Adverse Events

Initial Safety and Immunogenicity (Part 1)

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Safety, Immunogenicity, and Plasma Collection (Part 2)

Serious events: 0 serious events

Other events: 34 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Dr. Jessica Khouri

California Department of Public Health

Phone: 510-231-7600

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Other adverse events
Measure	Initial Safety and Immunogenicity (Part 1) n=8 participants at risk Part 1 included scheduled assessments of the safety and immunogenicity of a single 40 µg dose of rBV A/B over a 12-week period with a safety follow-up at 6 months.	Safety, Immunogenicity, and Plasma Collection (Part 2) n=37 participants at risk Part 2 was conducted to collect source plasma for potential use in the production of BabyBIG® and to assess safety and immunogenicity of a single 40 µg dose of over a 12-week period; Part 2 included a follow-up for safety assessment at 6 months. Participants in Part 2 did not participate in Part 1.
Blood and lymphatic system disorders Lymphopenia	12.5% 1/8 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.	0.00% 0/37 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.
Blood and lymphatic system disorders Neutropenia	12.5% 1/8 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.	0.00% 0/37 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.
Gastrointestinal disorders Constipation	0.00% 0/8 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.	5.4% 2/37 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.
Gastrointestinal disorders Diarrhoea	12.5% 1/8 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.	5.4% 2/37 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.
Gastrointestinal disorders Nausea*	0.00% 0/8 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.	8.1% 3/37 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.
General disorders Chills*	0.00% 0/8 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.	5.4% 2/37 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.
General disorders Injection site anaesthesia*	12.5% 1/8 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.	0.00% 0/37 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.
General disorders Injection site erythema*	62.5% 5/8 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.	51.4% 19/37 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.
General disorders Injection site induration*	0.00% 0/8 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.	8.1% 3/37 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.
General disorders Injection site nodule*	0.00% 0/8 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.	5.4% 2/37 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.
General disorders Injection site pain*	75.0% 6/8 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.	40.5% 15/37 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.
General disorders Injection site papule	12.5% 1/8 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.	0.00% 0/37 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.
General disorders Injection site pruritus*	37.5% 3/8 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.	24.3% 9/37 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.
General disorders Injection site reaction*	12.5% 1/8 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.	0.00% 0/37 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.
General disorders Injection site swelling*	37.5% 3/8 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.	48.6% 18/37 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.
General disorders Injection site urticaria*	0.00% 0/8 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.	2.7% 1/37 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.
General disorders Malaise*	0.00% 0/8 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.	13.5% 5/37 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.
General disorders Pain*	0.00% 0/8 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.	2.7% 1/37 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.
General disorders Pyrexia*	0.00% 0/8 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.	5.4% 2/37 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.
General disorders Swelling*	0.00% 0/8 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.	8.1% 3/37 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.
Infections and infestations Nasopharyngitis	0.00% 0/8 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.	2.7% 1/37 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.
Infections and infestations Staphylococcal infection	0.00% 0/8 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.	2.7% 1/37 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.
Infections and infestations Tonsillitis	0.00% 0/8 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.	2.7% 1/37 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.
Infections and infestations Tooth infection	0.00% 0/8 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.	2.7% 1/37 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.
Infections and infestations Upper respiratory tract infection	12.5% 1/8 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.	2.7% 1/37 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.
Injury, poisoning and procedural complications Infusion site hematoma	0.00% 0/8 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.	2.7% 1/37 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.
Injury, poisoning and procedural complications Injection site swelling*	0.00% 0/8 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.	2.7% 1/37 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.
Injury, poisoning and procedural complications Procedural complication*	0.00% 0/8 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.	37.8% 14/37 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.
Injury, poisoning and procedural complications Procedural pain	0.00% 0/8 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.	8.1% 3/37 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.
Investigations Aspartate aminotransferase increased*	0.00% 0/8 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.	2.7% 1/37 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.
Investigations Blood potassium increased	0.00% 0/8 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.	2.7% 1/37 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.
Investigations Blood urea increased	0.00% 0/8 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.	2.7% 1/37 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.
Investigations Blood urine present	12.5% 1/8 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.	0.00% 0/37 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.
Investigations Body temperature increased*	0.00% 0/8 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.	2.7% 1/37 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.
Investigations Haematocrit decreased	0.00% 0/8 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.	13.5% 5/37 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.
Investigations Haemaglobin decreased	12.5% 1/8 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.	2.7% 1/37 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.
Investigations Haemaglobin increased	0.00% 0/8 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.	2.7% 1/37 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.
Investigations Platelet count decreased	12.5% 1/8 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.	0.00% 0/37 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.
Investigations Protein total decreased	0.00% 0/8 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.	5.4% 2/37 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.
Investigations Urine ketone body present	0.00% 0/8 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.	2.7% 1/37 • Six months following rBV A/B administration Adverse events (AEs) indicated with \* were largely classified as treatment-related reactions (TRRs). Of the 32 and 186 total AEs in Parts 1 and 2, respectively, 21 (65.6%) and 117 (62.9%) were TRRs within the indicated categories. Also, of the 21 and 117 TRRs in Parts 1 and 2, respectively, 19 (90.5%) and 97 (82.9%) occurred within 7 days of the rBV A/B injection, and 8 of 8 participants in Part 1 (100%) and 30 of 37 in Part 2 (81.1%) had at least one TRR within 7 days of the rBV A/B injection.