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

• ClinicalTrials.gov Identifier: NCT03471078
• Recruitment Status: Completed
• First Posted: March 20, 2018
• Results First Posted: November 24, 2021
• Last Update Posted: April 20, 2023
• Sponsor: Sobi, Inc.
• Information provided by (Responsible Party): Sobi, Inc.

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Supportive Care
• Condition: Chemotherapy-induced Thrombocytopenia
• Interventions: Drug: Avatrombopag; Drug: Placebo Oral Tablet
• Enrollment: 122

Participant Flow

Recruitment Details	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.
Pre-assignment Details	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.

Arm/Group Title	Avatrombopag	Placebo
Arm/Group Description	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	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
Period Title: Overall Study
Started	82	40
Completed	61	34
Not Completed	21	6
Reason Not Completed
Withdrawal by Subject	9	1
Adverse Event	4	1
Physician Decision	3	2
Death	2	0
Other	3	2

Baseline Characteristics

Arm/Group Title		Avatrombopag	Placebo	Total
Arm/Group Description		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	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 of all reporting groups
Overall Number of Baseline Participants		82	40	122
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
Age at Enrollment	Number Analyzed	82 participants	40 participants	122 participants
		61.0 (10.08)	60.8 (10.41)	61.0 (10.15)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	82 participants	40 participants	122 participants
	Female	43 52.4%	22 55.0%	65 53.3%
	Male	39 47.6%	18 45.0%	57 46.7%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	82 participants	40 participants	122 participants
	Hispanic or Latino	0 0.0%	0 0.0%	0 0.0%
	Not Hispanic or Latino	78 95.1%	37 92.5%	115 94.3%
	Unknown or Not Reported	4 4.9%	3 7.5%	7 5.7%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	82 participants	40 participants	122 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%
	Asian	5 6.1%	3 7.5%	8 6.6%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	0 0.0%	0 0.0%	0 0.0%
	White	77 93.9%	37 92.5%	114 93.4%
	More than one race	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
ECOG Performance Status [1]; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	82 participants	40 participants	122 participants
Subjects with ECOG Score 0		21 25.6%	8 20.0%	29 23.8%
Subjects with ECOG Score 1		60 73.2%	31 77.5%	91 74.6%
Subjects with ECOG Score 2		1 1.2%	1 2.5%	2 1.6%
		[1] Measure Description: The Eastern Cooperative Oncology Group (ECOG) performance status score describes a patient's level of functioning in terms of their ability to care for themself, daily activity, and physical ability (walking, working, etc.). 0=Fully active, able to carry on all pre-disease performance without restriction 1=Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work 2=Ambulatory and capable of all selfcare but unable to carry out any work activities; up and about more than 50% of waking hours
Number of Eligible Chemotherapy Agents Currently Receiving per IWRS; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	82 participants	40 participants	122 participants
Subjects Receiving 1 Agent		40 48.8%	20 50.0%	60 49.2%
Subjects Receiving ≥ 2 Agents		42 51.2%	20 50.0%	62 50.8%
Baseline Platelet Count (x10⁹/L); Mean (Standard Deviation); Unit of measure: Platelets x10⁹/L
	Number Analyzed	82 participants	40 participants	122 participants
		29.6 (13.66)	33.0 (11.49)	30.7 (13.04)
Height (cm); Mean (Standard Deviation); Unit of measure: Cm
	Number Analyzed	82 participants	40 participants	122 participants
		166.3 (10.17)	166.2 (10.32)	166.3 (10.18)
Weight (kg); Mean (Standard Deviation); Unit of measure: Kg
	Number Analyzed	82 participants	40 participants	122 participants
		76.2 (17.73)	78.8 (17.64)	77.0 (17.67)
BMI (kg/m²); Mean (Standard Deviation); Unit of measure: Kg/m²
	Number Analyzed	82 participants	40 participants	122 participants
		27.7 (6.56)	28.5 (5.58)	27.9 (6.24)

Outcome Measures

1. Primary Outcome

Title	Percentage of Subjects Who do Not Require Platelet Transfusion, Dose Reduction in Chemotherapy by 15%, or Chemotherapy Delay by >=4 Days
Description	[Not Specified]
Time Frame	Randomization up to 33 days

Outcome Measure Data

Analysis Population Description

All randomized subjects

Arm/Group Title	Avatrombopag	Placebo
Arm/Group Description:	Avatrombopag: Oral avatrombopag tablet	Placebo Oral Tablet: Placebo comparator tablet
Overall Number of Participants Analyzed	82	40
Measure Type: Count of Participants; Unit of Measure: Participants
	57 69.5%	29 72.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Avatrombopag, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	The primary efficacy endpoint was tested between avatrombopag and placebo using the Cochran-Mantel-Haenszel 2-sided test at α=0.05, adjusting for the number of eligible chemotherapy agents as collected in IWRS (1 or ≥2 permissible chemotherapy agents).
Statistical Test of Hypothesis	P-Value	0.7186
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3.0
	Confidence Interval	(2-Sided) 95%; -21.7 to 15.6
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	Duration of Severe Thrombocytopenia Defined as a Platelet Count <50 x 10^9/L
Description	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.
Time Frame	Randomization up to 33 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Avatrombopag	Placebo
Arm/Group Description:	Avatrombopag: Oral avatrombopag tablet	Placebo Oral Tablet: Placebo comparator tablet
Overall Number of Participants Analyzed	81	40
Mean (Standard Deviation); Unit of Measure: Days
	4.6 (5.53)	4.7 (6.56)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Avatrombopag, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.8372
	Comments	[Not Specified]
	Method	Van Elteren Test
	Comments	[Not Specified]

3. Secondary Outcome

Title	Change in Platelet Count From Baseline (Nadir)
Description	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.
Time Frame	Randomization up to 33 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Avatrombopag	Placebo
Arm/Group Description:	Avatrombopag: Oral avatrombopag tablet	Placebo Oral Tablet: Placebo comparator tablet
Overall Number of Participants Analyzed	82	40
Mean (Standard Deviation); Unit of Measure: Platelets x 10^9/L
	51.5 (61.85)	29.1 (39.48)

4. Secondary Outcome

Title	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.
Description	[Not Specified]
Time Frame	Randomization up to 33 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Avatrombopag	Placebo
Arm/Group Description:	Avatrombopag: Oral avatrombopag tablet	Placebo Oral Tablet: Placebo comparator tablet
Overall Number of Participants Analyzed	82	40
Measure Type: Count of Participants; Unit of Measure: Participants
	82 100.0%	40 100.0%

Adverse Events

Time Frame	Adverse event data were collected during the Double-Blind Treatment Phase and included two 21- or 28-day chemotherapy cycles.
Adverse Event Reporting Description	Adverse events were assessed by Investigators at each study visit.
Arm/Group Title	Avatrombopag	Placebo
Arm/Group Description	Avatrombopag: Oral avatrombopag tablet	Placebo Oral Tablet: Placebo comparator tablet
All-Cause Mortality
	Avatrombopag	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	2/82 (2.44%)	0/40 (0.00%)
Serious Adverse Events
	Avatrombopag	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	16/82 (19.51%)	8/40 (20.00%)
Blood and lymphatic system disorders
Thrombocytopenia † 1	4/82 (4.88%)	4/40 (10.00%)
Pancytopenia † 1	3/82 (3.66%)	0/40 (0.00%)
Anaemia † 1	1/82 (1.22%)	2/40 (5.00%)
Febrile neutropenia † 1	1/82 (1.22%)	0/40 (0.00%)
Leukocytosis † 1	1/82 (1.22%)	0/40 (0.00%)
Leukopenia † 1	1/82 (1.22%)	1/40 (2.50%)
Neutropenia † 1	0/82 (0.00%)	2/40 (5.00%)
Gastrointestinal disorders
Stomatitis † 1	1/82 (1.22%)	0/40 (0.00%)
Infections and infestations
Pneumonia † 1	1/82 (1.22%)	1/40 (2.50%)
Investigations
Blood lactate dehydrogenase increase † 1	1/82 (1.22%)	0/40 (0.00%)
Nervous system disorders
Ischaemic cerebral infarction † 1	1/82 (1.22%)	0/40 (0.00%)
Lacunar infarction † 1	1/82 (1.22%)	0/40 (0.00%)
Cerebral ischaemia † 1	0/82 (0.00%)	1/40 (2.50%)
Respiratory, thoracic and mediastinal disorders
Non-small cell lung cancer † 1	1/82 (1.22%)	0/40 (0.00%)
Vascular disorders
Capillary leak syndrome † 1	1/82 (1.22%)	0/40 (0.00%)
1 Term from vocabulary, MedDRA (23.0); † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Avatrombopag	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	71/82 (86.59%)	36/40 (90.00%)
Blood and lymphatic system disorders
Anaemia † 1	32/82 (39.02%)	21/40 (52.50%)
Leukopenia † 1	24/82 (29.27%)	15/40 (37.50%)
Neutropenia † 1	24/82 (29.27%)	17/40 (42.50%)
Thrombocytopenia † 1	15/82 (18.29%)	13/40 (32.50%)
Thombocytosis † 1	9/82 (10.98%)	2/40 (5.00%)
Gastrointestinal disorders
Nausea † 1	6/82 (7.32%)	6/40 (15.00%)
Vomiting † 1	5/82 (6.10%)	0/40 (0.00%)
General disorders
Asthenia † 1	5/82 (6.10%)	4/40 (10.00%)
Fatigue † 1	3/82 (3.66%)	3/40 (7.50%)
Respiratory, thoracic and mediastinal disorders
Epistaxis † 1	4/82 (4.88%)	2/40 (5.00%)
1 Term from vocabulary, MedDRA (23.0); † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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.

Results Point of Contact

• Name/Title: VP of Global Drug Development
• Organization: Dova
• Phone: 9193387864
• EMail: clinical@dova.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Al-Samkari H, Kolb-Sielecki J, Safina SZ, Xue X, Jamieson BD. Avatrombopag for chemotherapy-induced thrombocytopenia in patients with non-haematological malignancies: an international, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Haematol. 2022 Mar;9(3):e179-e189. doi: 10.1016/S2352-3026(22)00001-1.

• Responsible Party: Sobi, Inc.
• ClinicalTrials.gov Identifier: NCT03471078
• Other Study ID Numbers: AVA-CIT-330
• First Submitted: March 7, 2018
• First Posted: March 20, 2018
• Results First Submitted: September 10, 2021
• Results First Posted: November 24, 2021
• Last Update Posted: April 20, 2023