Trial Outcomes & Findings for A Phase 1b Open Label, Dose Escalation Study of PLX3397 in Combination With Vemurafenib in V600-mutated BRAF Melanoma (NCT NCT01826448)

NCT ID: NCT01826448

Last Updated: 2020-05-28

Results Overview

Recruitment status

TERMINATED

Study phase

PHASE1

Target enrollment

13 participants

Primary outcome timeframe

1 year

Results posted on

2020-05-28

Participant Flow

A total of 13 participants who met all inclusion and none of the exclusion criteria were enrolled in the study.

This was an open-label, multicenter, Phase 1b, dose-escalation study, followed by an Extension Phase at the recommended Phase 2 dose (RP2D) of both drugs. During Dose-escalation (planned n=40), cohorts of 3 to 6 participants were enrolled to identify the RP2D of each agent to be administered to patients enrolled in the subsequent Extension Phase.

Participant milestones

Participant milestones
Measure	Cohort 1; PLX3397 800 mg/Day + Vemurafenib 720 mg BID Participant who received 800 mg/day (400 twice daily \[BID\]) of PLX3397 and 720 mg BID of vemurafenib.	Cohort 2; PLX3397 800 mg/Day + Vemurafenib 960 mg BID Participants who received 800 mg/day (400 twice daily \[BID\]) of PLX3397 and 960 mg BID of vemurafenib.
Overall Study STARTED	4	9
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	4	9

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort 1; PLX3397 800 mg/Day + Vemurafenib 720 mg BID Participant who received 800 mg/day (400 twice daily \[BID\]) of PLX3397 and 720 mg BID of vemurafenib.	Cohort 2; PLX3397 800 mg/Day + Vemurafenib 960 mg BID Participants who received 800 mg/day (400 twice daily \[BID\]) of PLX3397 and 960 mg BID of vemurafenib.
Overall Study Adverse Event	1	3
Overall Study Disease progression	2	4
Overall Study Withdrawal by Subject	1	0
Overall Study Physician Decision	0	1
Overall Study 2 active cancers	0	1

Baseline Characteristics

A Phase 1b Open Label, Dose Escalation Study of PLX3397 in Combination With Vemurafenib in V600-mutated BRAF Melanoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1; PLX3397 800 mg/Day + Vemurafenib 720 mg BID n=4 Participants Participant who received 800 mg/day (400 twice daily \[BID\]) of PLX3397 and 720 mg BID of vemurafenib.	Cohort 2; PLX3397 800 mg/Day + Vemurafenib 960 mg BID n=9 Participants Participants who received 800 mg/day (400 twice daily \[BID\]) of PLX3397 and 960 mg BID of vemurafenib.	Total n=13 Participants Total of all reporting groups
Age, Continuous	42 years n=5 Participants	60.1 years n=7 Participants	54.5 years n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants

PRIMARY outcome

Timeframe: 1 year

Population: Adverse events (AEs) were assessed in the modified intent-to-treat population (mITT).

Outcome measures

Outcome measures
Measure	Cohort 1; PLX3397 800 mg/Day + Vemurafenib 720 mg BID n=4 Participants Participant who received 800 mg/day (400 twice daily \[BID\]) of PLX3397 and 720 mg BID of vemurafenib.	Cohort 2; PLX3397 800 mg/Day + Vemurafenib 960 mg BID n=9 Participants Participants who received 800 mg/day (400 twice daily \[BID\]) of PLX3397 and 960 mg BID of vemurafenib.
Percentage of Participants With Adverse Events Who Received PLX3397 in Combination With Vemurafenib in V600-mutated BRAF Melanoma Any primary system organ class	100 percentage of participants	100 percentage of participants
Percentage of Participants With Adverse Events Who Received PLX3397 in Combination With Vemurafenib in V600-mutated BRAF Melanoma Any AE	100 percentage of participants	100 percentage of participants
Percentage of Participants With Adverse Events Who Received PLX3397 in Combination With Vemurafenib in V600-mutated BRAF Melanoma AEs related to both PLX3397 and vemurafenib	100 percentage of participants	55.6 percentage of participants
Percentage of Participants With Adverse Events Who Received PLX3397 in Combination With Vemurafenib in V600-mutated BRAF Melanoma AEs related to PLX3397	75 percentage of participants	77.8 percentage of participants
Percentage of Participants With Adverse Events Who Received PLX3397 in Combination With Vemurafenib in V600-mutated BRAF Melanoma AEs related vemurafenib	25 percentage of participants	77.8 percentage of participants
Percentage of Participants With Adverse Events Who Received PLX3397 in Combination With Vemurafenib in V600-mutated BRAF Melanoma AEs leading to withdrawal from any study treatment	25 percentage of participants	44.4 percentage of participants
Percentage of Participants With Adverse Events Who Received PLX3397 in Combination With Vemurafenib in V600-mutated BRAF Melanoma AEs considered as dose limiting toxicities	25 percentage of participants	33.3 percentage of participants
Percentage of Participants With Adverse Events Who Received PLX3397 in Combination With Vemurafenib in V600-mutated BRAF Melanoma Serious adverse events	0 percentage of participants	44.4 percentage of participants
Percentage of Participants With Adverse Events Who Received PLX3397 in Combination With Vemurafenib in V600-mutated BRAF Melanoma Serious adverse events related to study treatment	0 percentage of participants	22.2 percentage of participants
Percentage of Participants With Adverse Events Who Received PLX3397 in Combination With Vemurafenib in V600-mutated BRAF Melanoma Adverse events leading to death	0 percentage of participants	0 percentage of participants

Adverse Events

Cohort 1; PLX3397 800 mg/Day + Vemurafenib 720 mg BID

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Cohort 2; PLX3397 800 mg/Day + Vemurafenib 960 mg BID

Serious events: 4 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Cohort 1; PLX3397 800 mg/Day + Vemurafenib 720 mg BID n=4 participants at risk Participant who received 800 mg/day (400 twice daily \[BID\] of PLX3397 and 720 mg BID of vemurafenib.	Cohort 2; PLX3397 800 mg/Day + Vemurafenib 960 mg BID n=9 participants at risk Participants who received 800 mg/day (400 twice daily \[BID\]) of PLX3397 and 960 mg BID of vemurafenib.
Investigations Alanine aminotransferase increased	0.00% 0/4 • Adverse events (and serious AEs [SAEs]) were recorded from the time the participant received the first dose of study drug up to 28 days after the last dose, up to 1 year (mITT population). Other non-serious adverse events occurring in ≥ 9 participants by system organ class or ≥ 3 participants by preferred term are reported from the mITT population.	22.2% 2/9 • Adverse events (and serious AEs [SAEs]) were recorded from the time the participant received the first dose of study drug up to 28 days after the last dose, up to 1 year (mITT population). Other non-serious adverse events occurring in ≥ 9 participants by system organ class or ≥ 3 participants by preferred term are reported from the mITT population.
Investigations Neutrophil count decreased	0.00% 0/4 • Adverse events (and serious AEs [SAEs]) were recorded from the time the participant received the first dose of study drug up to 28 days after the last dose, up to 1 year (mITT population). Other non-serious adverse events occurring in ≥ 9 participants by system organ class or ≥ 3 participants by preferred term are reported from the mITT population.	11.1% 1/9 • Adverse events (and serious AEs [SAEs]) were recorded from the time the participant received the first dose of study drug up to 28 days after the last dose, up to 1 year (mITT population). Other non-serious adverse events occurring in ≥ 9 participants by system organ class or ≥ 3 participants by preferred term are reported from the mITT population.
Infections and infestations Cellulitis	0.00% 0/4 • Adverse events (and serious AEs [SAEs]) were recorded from the time the participant received the first dose of study drug up to 28 days after the last dose, up to 1 year (mITT population). Other non-serious adverse events occurring in ≥ 9 participants by system organ class or ≥ 3 participants by preferred term are reported from the mITT population.	11.1% 1/9 • Adverse events (and serious AEs [SAEs]) were recorded from the time the participant received the first dose of study drug up to 28 days after the last dose, up to 1 year (mITT population). Other non-serious adverse events occurring in ≥ 9 participants by system organ class or ≥ 3 participants by preferred term are reported from the mITT population.
General disorders Pyrexia	0.00% 0/4 • Adverse events (and serious AEs [SAEs]) were recorded from the time the participant received the first dose of study drug up to 28 days after the last dose, up to 1 year (mITT population). Other non-serious adverse events occurring in ≥ 9 participants by system organ class or ≥ 3 participants by preferred term are reported from the mITT population.	11.1% 1/9 • Adverse events (and serious AEs [SAEs]) were recorded from the time the participant received the first dose of study drug up to 28 days after the last dose, up to 1 year (mITT population). Other non-serious adverse events occurring in ≥ 9 participants by system organ class or ≥ 3 participants by preferred term are reported from the mITT population.
Investigations Blood alkaline phosphatase increased	0.00% 0/4 • Adverse events (and serious AEs [SAEs]) were recorded from the time the participant received the first dose of study drug up to 28 days after the last dose, up to 1 year (mITT population). Other non-serious adverse events occurring in ≥ 9 participants by system organ class or ≥ 3 participants by preferred term are reported from the mITT population.	11.1% 1/9 • Adverse events (and serious AEs [SAEs]) were recorded from the time the participant received the first dose of study drug up to 28 days after the last dose, up to 1 year (mITT population). Other non-serious adverse events occurring in ≥ 9 participants by system organ class or ≥ 3 participants by preferred term are reported from the mITT population.
Investigations Aspartate aminotransferase increased	0.00% 0/4 • Adverse events (and serious AEs [SAEs]) were recorded from the time the participant received the first dose of study drug up to 28 days after the last dose, up to 1 year (mITT population). Other non-serious adverse events occurring in ≥ 9 participants by system organ class or ≥ 3 participants by preferred term are reported from the mITT population.	22.2% 2/9 • Adverse events (and serious AEs [SAEs]) were recorded from the time the participant received the first dose of study drug up to 28 days after the last dose, up to 1 year (mITT population). Other non-serious adverse events occurring in ≥ 9 participants by system organ class or ≥ 3 participants by preferred term are reported from the mITT population.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/4 • Adverse events (and serious AEs [SAEs]) were recorded from the time the participant received the first dose of study drug up to 28 days after the last dose, up to 1 year (mITT population). Other non-serious adverse events occurring in ≥ 9 participants by system organ class or ≥ 3 participants by preferred term are reported from the mITT population.	11.1% 1/9 • Adverse events (and serious AEs [SAEs]) were recorded from the time the participant received the first dose of study drug up to 28 days after the last dose, up to 1 year (mITT population). Other non-serious adverse events occurring in ≥ 9 participants by system organ class or ≥ 3 participants by preferred term are reported from the mITT population.
Nervous system disorders Cerebellar haemorrhage	0.00% 0/4 • Adverse events (and serious AEs [SAEs]) were recorded from the time the participant received the first dose of study drug up to 28 days after the last dose, up to 1 year (mITT population). Other non-serious adverse events occurring in ≥ 9 participants by system organ class or ≥ 3 participants by preferred term are reported from the mITT population.	11.1% 1/9 • Adverse events (and serious AEs [SAEs]) were recorded from the time the participant received the first dose of study drug up to 28 days after the last dose, up to 1 year (mITT population). Other non-serious adverse events occurring in ≥ 9 participants by system organ class or ≥ 3 participants by preferred term are reported from the mITT population.

Other adverse events

Additional Information

Medical Director

Daiichi Sankyo Inc.

Phone: 908-992-6400

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Cohort 1; PLX3397 800 mg/Day + Vemurafenib 720 mg BID n=4 participants at risk Participant who received 800 mg/day (400 twice daily \[BID\] of PLX3397 and 720 mg BID of vemurafenib.	Cohort 2; PLX3397 800 mg/Day + Vemurafenib 960 mg BID n=9 participants at risk Participants who received 800 mg/day (400 twice daily \[BID\]) of PLX3397 and 960 mg BID of vemurafenib.
Blood and lymphatic system disorders Anaemia	25.0% 1/4 • Adverse events (and serious AEs [SAEs]) were recorded from the time the participant received the first dose of study drug up to 28 days after the last dose, up to 1 year (mITT population). Other non-serious adverse events occurring in ≥ 9 participants by system organ class or ≥ 3 participants by preferred term are reported from the mITT population.	44.4% 4/9 • Adverse events (and serious AEs [SAEs]) were recorded from the time the participant received the first dose of study drug up to 28 days after the last dose, up to 1 year (mITT population). Other non-serious adverse events occurring in ≥ 9 participants by system organ class or ≥ 3 participants by preferred term are reported from the mITT population.
Gastrointestinal disorders Constipation	0.00% 0/4 • Adverse events (and serious AEs [SAEs]) were recorded from the time the participant received the first dose of study drug up to 28 days after the last dose, up to 1 year (mITT population). Other non-serious adverse events occurring in ≥ 9 participants by system organ class or ≥ 3 participants by preferred term are reported from the mITT population.	33.3% 3/9 • Adverse events (and serious AEs [SAEs]) were recorded from the time the participant received the first dose of study drug up to 28 days after the last dose, up to 1 year (mITT population). Other non-serious adverse events occurring in ≥ 9 participants by system organ class or ≥ 3 participants by preferred term are reported from the mITT population.
Gastrointestinal disorders Diarrhoea	25.0% 1/4 • Adverse events (and serious AEs [SAEs]) were recorded from the time the participant received the first dose of study drug up to 28 days after the last dose, up to 1 year (mITT population). Other non-serious adverse events occurring in ≥ 9 participants by system organ class or ≥ 3 participants by preferred term are reported from the mITT population.	44.4% 4/9 • Adverse events (and serious AEs [SAEs]) were recorded from the time the participant received the first dose of study drug up to 28 days after the last dose, up to 1 year (mITT population). Other non-serious adverse events occurring in ≥ 9 participants by system organ class or ≥ 3 participants by preferred term are reported from the mITT population.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/4 • Adverse events (and serious AEs [SAEs]) were recorded from the time the participant received the first dose of study drug up to 28 days after the last dose, up to 1 year (mITT population). Other non-serious adverse events occurring in ≥ 9 participants by system organ class or ≥ 3 participants by preferred term are reported from the mITT population.	33.3% 3/9 • Adverse events (and serious AEs [SAEs]) were recorded from the time the participant received the first dose of study drug up to 28 days after the last dose, up to 1 year (mITT population). Other non-serious adverse events occurring in ≥ 9 participants by system organ class or ≥ 3 participants by preferred term are reported from the mITT population.
Gastrointestinal disorders Nausea	25.0% 1/4 • Adverse events (and serious AEs [SAEs]) were recorded from the time the participant received the first dose of study drug up to 28 days after the last dose, up to 1 year (mITT population). Other non-serious adverse events occurring in ≥ 9 participants by system organ class or ≥ 3 participants by preferred term are reported from the mITT population.	33.3% 3/9 • Adverse events (and serious AEs [SAEs]) were recorded from the time the participant received the first dose of study drug up to 28 days after the last dose, up to 1 year (mITT population). Other non-serious adverse events occurring in ≥ 9 participants by system organ class or ≥ 3 participants by preferred term are reported from the mITT population.
Gastrointestinal disorders Vomiting	50.0% 2/4 • Adverse events (and serious AEs [SAEs]) were recorded from the time the participant received the first dose of study drug up to 28 days after the last dose, up to 1 year (mITT population). Other non-serious adverse events occurring in ≥ 9 participants by system organ class or ≥ 3 participants by preferred term are reported from the mITT population.	33.3% 3/9 • Adverse events (and serious AEs [SAEs]) were recorded from the time the participant received the first dose of study drug up to 28 days after the last dose, up to 1 year (mITT population). Other non-serious adverse events occurring in ≥ 9 participants by system organ class or ≥ 3 participants by preferred term are reported from the mITT population.
General disorders Fatigue	25.0% 1/4 • Adverse events (and serious AEs [SAEs]) were recorded from the time the participant received the first dose of study drug up to 28 days after the last dose, up to 1 year (mITT population). Other non-serious adverse events occurring in ≥ 9 participants by system organ class or ≥ 3 participants by preferred term are reported from the mITT population.	77.8% 7/9 • Adverse events (and serious AEs [SAEs]) were recorded from the time the participant received the first dose of study drug up to 28 days after the last dose, up to 1 year (mITT population). Other non-serious adverse events occurring in ≥ 9 participants by system organ class or ≥ 3 participants by preferred term are reported from the mITT population.
General disorders Pyrexia	0.00% 0/4 • Adverse events (and serious AEs [SAEs]) were recorded from the time the participant received the first dose of study drug up to 28 days after the last dose, up to 1 year (mITT population). Other non-serious adverse events occurring in ≥ 9 participants by system organ class or ≥ 3 participants by preferred term are reported from the mITT population.	44.4% 4/9 • Adverse events (and serious AEs [SAEs]) were recorded from the time the participant received the first dose of study drug up to 28 days after the last dose, up to 1 year (mITT population). Other non-serious adverse events occurring in ≥ 9 participants by system organ class or ≥ 3 participants by preferred term are reported from the mITT population.
Investigations Alanine aminotransferase increased	25.0% 1/4 • Adverse events (and serious AEs [SAEs]) were recorded from the time the participant received the first dose of study drug up to 28 days after the last dose, up to 1 year (mITT population). Other non-serious adverse events occurring in ≥ 9 participants by system organ class or ≥ 3 participants by preferred term are reported from the mITT population.	22.2% 2/9 • Adverse events (and serious AEs [SAEs]) were recorded from the time the participant received the first dose of study drug up to 28 days after the last dose, up to 1 year (mITT population). Other non-serious adverse events occurring in ≥ 9 participants by system organ class or ≥ 3 participants by preferred term are reported from the mITT population.
Investigations Aspartate aminotransferase increased	50.0% 2/4 • Adverse events (and serious AEs [SAEs]) were recorded from the time the participant received the first dose of study drug up to 28 days after the last dose, up to 1 year (mITT population). Other non-serious adverse events occurring in ≥ 9 participants by system organ class or ≥ 3 participants by preferred term are reported from the mITT population.	55.6% 5/9 • Adverse events (and serious AEs [SAEs]) were recorded from the time the participant received the first dose of study drug up to 28 days after the last dose, up to 1 year (mITT population). Other non-serious adverse events occurring in ≥ 9 participants by system organ class or ≥ 3 participants by preferred term are reported from the mITT population.
Investigations Blood alkaline phosphatase increased	25.0% 1/4 • Adverse events (and serious AEs [SAEs]) were recorded from the time the participant received the first dose of study drug up to 28 days after the last dose, up to 1 year (mITT population). Other non-serious adverse events occurring in ≥ 9 participants by system organ class or ≥ 3 participants by preferred term are reported from the mITT population.	44.4% 4/9 • Adverse events (and serious AEs [SAEs]) were recorded from the time the participant received the first dose of study drug up to 28 days after the last dose, up to 1 year (mITT population). Other non-serious adverse events occurring in ≥ 9 participants by system organ class or ≥ 3 participants by preferred term are reported from the mITT population.
Investigations Blood bilirubin increased	0.00% 0/4 • Adverse events (and serious AEs [SAEs]) were recorded from the time the participant received the first dose of study drug up to 28 days after the last dose, up to 1 year (mITT population). Other non-serious adverse events occurring in ≥ 9 participants by system organ class or ≥ 3 participants by preferred term are reported from the mITT population.	33.3% 3/9 • Adverse events (and serious AEs [SAEs]) were recorded from the time the participant received the first dose of study drug up to 28 days after the last dose, up to 1 year (mITT population). Other non-serious adverse events occurring in ≥ 9 participants by system organ class or ≥ 3 participants by preferred term are reported from the mITT population.
Investigations Blood creatinine increased	25.0% 1/4 • Adverse events (and serious AEs [SAEs]) were recorded from the time the participant received the first dose of study drug up to 28 days after the last dose, up to 1 year (mITT population). Other non-serious adverse events occurring in ≥ 9 participants by system organ class or ≥ 3 participants by preferred term are reported from the mITT population.	22.2% 2/9 • Adverse events (and serious AEs [SAEs]) were recorded from the time the participant received the first dose of study drug up to 28 days after the last dose, up to 1 year (mITT population). Other non-serious adverse events occurring in ≥ 9 participants by system organ class or ≥ 3 participants by preferred term are reported from the mITT population.
Investigations Lymphocyte count decreased	50.0% 2/4 • Adverse events (and serious AEs [SAEs]) were recorded from the time the participant received the first dose of study drug up to 28 days after the last dose, up to 1 year (mITT population). Other non-serious adverse events occurring in ≥ 9 participants by system organ class or ≥ 3 participants by preferred term are reported from the mITT population.	11.1% 1/9 • Adverse events (and serious AEs [SAEs]) were recorded from the time the participant received the first dose of study drug up to 28 days after the last dose, up to 1 year (mITT population). Other non-serious adverse events occurring in ≥ 9 participants by system organ class or ≥ 3 participants by preferred term are reported from the mITT population.
Investigations Weight decreased	50.0% 2/4 • Adverse events (and serious AEs [SAEs]) were recorded from the time the participant received the first dose of study drug up to 28 days after the last dose, up to 1 year (mITT population). Other non-serious adverse events occurring in ≥ 9 participants by system organ class or ≥ 3 participants by preferred term are reported from the mITT population.	11.1% 1/9 • Adverse events (and serious AEs [SAEs]) were recorded from the time the participant received the first dose of study drug up to 28 days after the last dose, up to 1 year (mITT population). Other non-serious adverse events occurring in ≥ 9 participants by system organ class or ≥ 3 participants by preferred term are reported from the mITT population.
Metabolism and nutrition disorders Decreased appetite	50.0% 2/4 • Adverse events (and serious AEs [SAEs]) were recorded from the time the participant received the first dose of study drug up to 28 days after the last dose, up to 1 year (mITT population). Other non-serious adverse events occurring in ≥ 9 participants by system organ class or ≥ 3 participants by preferred term are reported from the mITT population.	33.3% 3/9 • Adverse events (and serious AEs [SAEs]) were recorded from the time the participant received the first dose of study drug up to 28 days after the last dose, up to 1 year (mITT population). Other non-serious adverse events occurring in ≥ 9 participants by system organ class or ≥ 3 participants by preferred term are reported from the mITT population.
Musculoskeletal and connective tissue disorders Arthralgia	25.0% 1/4 • Adverse events (and serious AEs [SAEs]) were recorded from the time the participant received the first dose of study drug up to 28 days after the last dose, up to 1 year (mITT population). Other non-serious adverse events occurring in ≥ 9 participants by system organ class or ≥ 3 participants by preferred term are reported from the mITT population.	44.4% 4/9 • Adverse events (and serious AEs [SAEs]) were recorded from the time the participant received the first dose of study drug up to 28 days after the last dose, up to 1 year (mITT population). Other non-serious adverse events occurring in ≥ 9 participants by system organ class or ≥ 3 participants by preferred term are reported from the mITT population.
Skin and subcutaneous tissue disorders Photosensitivity reaction	25.0% 1/4 • Adverse events (and serious AEs [SAEs]) were recorded from the time the participant received the first dose of study drug up to 28 days after the last dose, up to 1 year (mITT population). Other non-serious adverse events occurring in ≥ 9 participants by system organ class or ≥ 3 participants by preferred term are reported from the mITT population.	22.2% 2/9 • Adverse events (and serious AEs [SAEs]) were recorded from the time the participant received the first dose of study drug up to 28 days after the last dose, up to 1 year (mITT population). Other non-serious adverse events occurring in ≥ 9 participants by system organ class or ≥ 3 participants by preferred term are reported from the mITT population.
Skin and subcutaneous tissue disorders Pruritus	25.0% 1/4 • Adverse events (and serious AEs [SAEs]) were recorded from the time the participant received the first dose of study drug up to 28 days after the last dose, up to 1 year (mITT population). Other non-serious adverse events occurring in ≥ 9 participants by system organ class or ≥ 3 participants by preferred term are reported from the mITT population.	33.3% 3/9 • Adverse events (and serious AEs [SAEs]) were recorded from the time the participant received the first dose of study drug up to 28 days after the last dose, up to 1 year (mITT population). Other non-serious adverse events occurring in ≥ 9 participants by system organ class or ≥ 3 participants by preferred term are reported from the mITT population.