Trial Outcomes & Findings for Avatrombopag for the Treatment of Chemotherapy-Induced Thrombocytopenia in Adults With Active Non-Hematological Cancers (NCT NCT03471078)

NCT ID: NCT03471078

Last Updated: 2023-09-28

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

122 participants

Primary outcome timeframe

Randomization up to 33 days

Results posted on

2023-09-28

Participant Flow

This was a Phase 3, randomized, double- blind, placebo controlled study of the efficacy and and safety of avatrombopag in subjects with chemotherapy induced thrombocytopenia and non active non-hematologic cancers. The study was conducted by qualified investigators at 71 sites in China, Hungary, Poland, Russia, Serbia, Ukraine, and the United States. The first subject was enrolled 12October2018.

The study was conducted by qualified investigators at 71 sites in China, Hungary, Poland, Russia, Serbia, Ukraine, and the United States. The first subject was enrolled 12October2018.

Participant milestones

Participant milestones
Measure	Avatrombopag Study is 2:1 randomization ratio (avatrombopag to placebo). 60 mg of Investigational product administered orally once daily for 5 days prior to chemotherapy and 5 days following chemotherapy treatment. Avatrombopag: Oral avatrombopag tablet	Placebo Study is 2:1 randomization ratio (avatrombopag to placebo). 60 mg Investigational product administered orally once daily for 5 days prior to chemotherapy and 5 days following chemotherapy treatment. Placebo Oral Tablet: Placebo comparator tablet
Overall Study STARTED	82	40
Overall Study COMPLETED	61	34
Overall Study NOT COMPLETED	21	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Avatrombopag Study is 2:1 randomization ratio (avatrombopag to placebo). 60 mg of Investigational product administered orally once daily for 5 days prior to chemotherapy and 5 days following chemotherapy treatment. Avatrombopag: Oral avatrombopag tablet	Placebo Study is 2:1 randomization ratio (avatrombopag to placebo). 60 mg Investigational product administered orally once daily for 5 days prior to chemotherapy and 5 days following chemotherapy treatment. Placebo Oral Tablet: Placebo comparator tablet
Overall Study Withdrawal by Subject	9	1
Overall Study Adverse Event	4	1
Overall Study Physician Decision	3	2
Overall Study Death	2	0
Overall Study Other	3	2

Baseline Characteristics

Avatrombopag for the Treatment of Chemotherapy-Induced Thrombocytopenia in Adults With Active Non-Hematological Cancers

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Avatrombopag n=82 Participants Study is 2:1 randomization ratio (avatrombopag to placebo). Investigational product administered orally once daily for 5 days prior to chemotherapy and 5 days following chemotherapy treatment. Avatrombopag: Oral avatrombopag tablet	Placebo n=40 Participants Study is 2:1 randomization ratio (avatrombopag to placebo). Investigational product administered orally once daily for 5 days prior to chemotherapy and 5 days following chemotherapy treatment. Placebo Oral Tablet: Placebo comparator tablet	Total n=122 Participants Total of all reporting groups
Age, Continuous Age at Enrollment	61.0 years STANDARD_DEVIATION 10.08 • n=5 Participants	60.8 years STANDARD_DEVIATION 10.41 • n=7 Participants	61.0 years STANDARD_DEVIATION 10.15 • n=5 Participants
Sex: Female, Male Female	43 Participants n=5 Participants	22 Participants n=7 Participants	65 Participants n=5 Participants
Sex: Female, Male Male	39 Participants n=5 Participants	18 Participants n=7 Participants	57 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	78 Participants n=5 Participants	37 Participants n=7 Participants	115 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	5 Participants n=5 Participants	3 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	77 Participants n=5 Participants	37 Participants n=7 Participants	114 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
ECOG Performance Status Subjects with ECOG Score 0	21 Participants n=5 Participants	8 Participants n=7 Participants	29 Participants n=5 Participants
ECOG Performance Status Subjects with ECOG Score 1	60 Participants n=5 Participants	31 Participants n=7 Participants	91 Participants n=5 Participants
ECOG Performance Status Subjects with ECOG Score 2	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Number of Eligible Chemotherapy Agents Currently Receiving per IWRS Subjects Receiving 1 Agent	40 Participants n=5 Participants	20 Participants n=7 Participants	60 Participants n=5 Participants
Number of Eligible Chemotherapy Agents Currently Receiving per IWRS Subjects Receiving ≥ 2 Agents	42 Participants n=5 Participants	20 Participants n=7 Participants	62 Participants n=5 Participants
Baseline Platelet Count (x10⁹/L)	29.6 platelets x10⁹/L STANDARD_DEVIATION 13.66 • n=5 Participants	33.0 platelets x10⁹/L STANDARD_DEVIATION 11.49 • n=7 Participants	30.7 platelets x10⁹/L STANDARD_DEVIATION 13.04 • n=5 Participants
Height (cm)	166.3 cm STANDARD_DEVIATION 10.17 • n=5 Participants	166.2 cm STANDARD_DEVIATION 10.32 • n=7 Participants	166.3 cm STANDARD_DEVIATION 10.18 • n=5 Participants
Weight (kg)	76.2 kg STANDARD_DEVIATION 17.73 • n=5 Participants	78.8 kg STANDARD_DEVIATION 17.64 • n=7 Participants	77.0 kg STANDARD_DEVIATION 17.67 • n=5 Participants
BMI (kg/m²)	27.7 kg/m² STANDARD_DEVIATION 6.56 • n=5 Participants	28.5 kg/m² STANDARD_DEVIATION 5.58 • n=7 Participants	27.9 kg/m² STANDARD_DEVIATION 6.24 • n=5 Participants

PRIMARY outcome

Timeframe: Randomization up to 33 days

Population: All randomized subjects

Outcome measures

Outcome measures
Measure	Avatrombopag n=82 Participants Avatrombopag: Oral avatrombopag tablet	Placebo n=40 Participants Placebo Oral Tablet: Placebo comparator tablet
Percentage of Subjects Who do Not Require Platelet Transfusion, Dose Reduction in Chemotherapy by 15%, or Chemotherapy Delay by >=4 Days	57 Participants	29 Participants

SECONDARY outcome

Timeframe: Randomization up to 33 days

The duration of severe thrombocytopenia is defined as the total number of days with a platelet count \<50×10\^9/L during the period after post-chemotherapy study drug treatment in Cycle X+1 through Chemotherapy Day of Cycle X+2.

Outcome measures

Outcome measures
Measure	Avatrombopag n=81 Participants Avatrombopag: Oral avatrombopag tablet	Placebo n=40 Participants Placebo Oral Tablet: Placebo comparator tablet
Duration of Severe Thrombocytopenia Defined as a Platelet Count <50 x 10^9/L	4.6 Days Standard Deviation 5.53	4.7 Days Standard Deviation 6.56

SECONDARY outcome

Timeframe: Randomization up to 33 days

Comparison of avatrombopag 60 mg vs. placebo, adjusted for the number of chemotherapy agents currently receiving per IWRS (1, ≥2). Cycle X nadir is defined as the lowest platelet count value prior to the first dose of study drug; Cycle X+1 nadir is defined as the lowest platelet count value during the period after post-chemotherapy study drug treatment in Cycle X+1 through Chemotherapy Day in Cycle X+2.

Outcome measures

Outcome measures
Measure	Avatrombopag n=82 Participants Avatrombopag: Oral avatrombopag tablet	Placebo n=40 Participants Placebo Oral Tablet: Placebo comparator tablet
Change in Platelet Count From Baseline (Nadir)	51.5 Platelets x 10^9/L Standard Deviation 61.85	29.1 Platelets x 10^9/L Standard Deviation 39.48

SECONDARY outcome

Timeframe: Randomization up to 33 days

Outcome measures

Outcome measures
Measure	Avatrombopag n=82 Participants Avatrombopag: Oral avatrombopag tablet	Placebo n=40 Participants Placebo Oral Tablet: Placebo comparator tablet
Percentage of Subjects Who Did Not Have Major or Non-major Clinically Relevant Bleeding During the Period After Post-chemotherapy Study Drug Treatment in Cycle X+1 Through Chemotherapy Day of Cycle X+2.	82 Participants	40 Participants

Adverse Events

Avatrombopag

Serious events: 16 serious events

Other events: 71 other events

Deaths: 2 deaths

Placebo

Serious events: 8 serious events

Other events: 36 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Avatrombopag n=82 participants at risk Avatrombopag: Oral avatrombopag tablet	Placebo n=40 participants at risk Placebo Oral Tablet: Placebo comparator tablet
Blood and lymphatic system disorders Anaemia	39.0% 32/82 • Adverse event data were collected during the Double-Blind Treatment Phase and included two 21- or 28-day chemotherapy cycles. Adverse events were assessed by Investigators at each study visit.	52.5% 21/40 • Adverse event data were collected during the Double-Blind Treatment Phase and included two 21- or 28-day chemotherapy cycles. Adverse events were assessed by Investigators at each study visit.
Blood and lymphatic system disorders Leukopenia	29.3% 24/82 • Adverse event data were collected during the Double-Blind Treatment Phase and included two 21- or 28-day chemotherapy cycles. Adverse events were assessed by Investigators at each study visit.	37.5% 15/40 • Adverse event data were collected during the Double-Blind Treatment Phase and included two 21- or 28-day chemotherapy cycles. Adverse events were assessed by Investigators at each study visit.
Blood and lymphatic system disorders Neutropenia	29.3% 24/82 • Adverse event data were collected during the Double-Blind Treatment Phase and included two 21- or 28-day chemotherapy cycles. Adverse events were assessed by Investigators at each study visit.	42.5% 17/40 • Adverse event data were collected during the Double-Blind Treatment Phase and included two 21- or 28-day chemotherapy cycles. Adverse events were assessed by Investigators at each study visit.
Blood and lymphatic system disorders Thrombocytopenia	18.3% 15/82 • Adverse event data were collected during the Double-Blind Treatment Phase and included two 21- or 28-day chemotherapy cycles. Adverse events were assessed by Investigators at each study visit.	32.5% 13/40 • Adverse event data were collected during the Double-Blind Treatment Phase and included two 21- or 28-day chemotherapy cycles. Adverse events were assessed by Investigators at each study visit.
Blood and lymphatic system disorders Thombocytosis	11.0% 9/82 • Adverse event data were collected during the Double-Blind Treatment Phase and included two 21- or 28-day chemotherapy cycles. Adverse events were assessed by Investigators at each study visit.	5.0% 2/40 • Adverse event data were collected during the Double-Blind Treatment Phase and included two 21- or 28-day chemotherapy cycles. Adverse events were assessed by Investigators at each study visit.
Gastrointestinal disorders Nausea	7.3% 6/82 • Adverse event data were collected during the Double-Blind Treatment Phase and included two 21- or 28-day chemotherapy cycles. Adverse events were assessed by Investigators at each study visit.	15.0% 6/40 • Adverse event data were collected during the Double-Blind Treatment Phase and included two 21- or 28-day chemotherapy cycles. Adverse events were assessed by Investigators at each study visit.
Gastrointestinal disorders Vomiting	6.1% 5/82 • Adverse event data were collected during the Double-Blind Treatment Phase and included two 21- or 28-day chemotherapy cycles. Adverse events were assessed by Investigators at each study visit.	0.00% 0/40 • Adverse event data were collected during the Double-Blind Treatment Phase and included two 21- or 28-day chemotherapy cycles. Adverse events were assessed by Investigators at each study visit.
General disorders Asthenia	6.1% 5/82 • Adverse event data were collected during the Double-Blind Treatment Phase and included two 21- or 28-day chemotherapy cycles. Adverse events were assessed by Investigators at each study visit.	10.0% 4/40 • Adverse event data were collected during the Double-Blind Treatment Phase and included two 21- or 28-day chemotherapy cycles. Adverse events were assessed by Investigators at each study visit.
General disorders Fatigue	3.7% 3/82 • Adverse event data were collected during the Double-Blind Treatment Phase and included two 21- or 28-day chemotherapy cycles. Adverse events were assessed by Investigators at each study visit.	7.5% 3/40 • Adverse event data were collected during the Double-Blind Treatment Phase and included two 21- or 28-day chemotherapy cycles. Adverse events were assessed by Investigators at each study visit.
Respiratory, thoracic and mediastinal disorders Epistaxis	4.9% 4/82 • Adverse event data were collected during the Double-Blind Treatment Phase and included two 21- or 28-day chemotherapy cycles. Adverse events were assessed by Investigators at each study visit.	5.0% 2/40 • Adverse event data were collected during the Double-Blind Treatment Phase and included two 21- or 28-day chemotherapy cycles. Adverse events were assessed by Investigators at each study visit.

Additional Information

VP of Global Drug Development

Dova

Phone: 9193387864

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The disclosure restriction on the PI is that the sponsor will review results communications prior to public release and can embargo communications regarding trial results.
Publication restrictions are in place

Restriction type: OTHER