Trial Outcomes & Findings for A Phase III PI-88 in the Adjuvant Treatment of Subjects With Hepatitis Virus Related HCC After Surgical Resection (NCT NCT01402908)

Last Updated: 2022-06-23

Results Overview

To evaluate the efficacy of daily administration of PI-88 versus placebo for the adjuvant treatment of study subjects as measured by DFS during study period. As the median DFS could not be estimated, the overall 25 th percentile DFS was reported.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

520 participants

Primary outcome timeframe

End of study

Results posted on

2022-06-23

Participant Flow

Participant milestones

Participant milestones
Measure	PI-88 Arm 1 PI-88: Lyophilized powder reconstituted to provide 160 mg of PI-88	Placebo Arm 2 Placebo: Lactose lyophilized powder
Overall Study STARTED	258	261
Overall Study COMPLETED	224	243
Overall Study NOT COMPLETED	34	18

Reasons for withdrawal

Reasons for withdrawal
Measure	PI-88 Arm 1 PI-88: Lyophilized powder reconstituted to provide 160 mg of PI-88	Placebo Arm 2 Placebo: Lactose lyophilized powder
Overall Study Withdrawal by Subject	30	17
Overall Study Lost to Follow-up	3	1
Overall Study Physician Decision	1	0

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	PI-88 n=258 Participants Arm 1 PI-88: Lyophilized powder reconstituted to provide 160 mg of PI-88	Placebo n=261 Participants Arm 2 Placebo: Lactose lyophilized powder	Total n=519 Participants Total of all reporting groups
Vascular Invasion Absent	134 Participants n=258 Participants	134 Participants n=261 Participants	268 Participants n=519 Participants
Baseline Hepatitis Serology Missing	0 Participants n=258 Participants	1 Participants n=261 Participants	1 Participants n=519 Participants
Baseline Hepatitis Serology HBV+ & HCV+	10 Participants n=258 Participants	13 Participants n=261 Participants	23 Participants n=519 Participants
Baseline Hepatitis Serology HBV+ Only	212 Participants n=258 Participants	222 Participants n=261 Participants	434 Participants n=519 Participants
Baseline Hepatitis Serology HCV+ Only	33 Participants n=258 Participants	20 Participants n=261 Participants	53 Participants n=519 Participants
Baseline Hepatitis Serology HBV- & HCV-	3 Participants n=258 Participants	5 Participants n=261 Participants	8 Participants n=519 Participants
Total Child-Pugh Score (categorized) Missing	1 units on a scale n=258 Participants	1 units on a scale n=261 Participants	2 units on a scale n=519 Participants
Age, Continuous	54.12 years STANDARD_DEVIATION 10.201 • n=258 Participants	55.08 years STANDARD_DEVIATION 9.619 • n=261 Participants	54.61 years STANDARD_DEVIATION 9.915 • n=519 Participants
Sex: Female, Male Female	52 Participants n=258 Participants	44 Participants n=261 Participants	96 Participants n=519 Participants
Sex: Female, Male Male	206 Participants n=258 Participants	217 Participants n=261 Participants	423 Participants n=519 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Region of Enrollment South Korea	106 participants n=258 Participants	96 participants n=261 Participants	202 participants n=519 Participants
Region of Enrollment Hong Kong	6 participants n=258 Participants	3 participants n=261 Participants	9 participants n=519 Participants
Region of Enrollment China	24 participants n=258 Participants	24 participants n=261 Participants	48 participants n=519 Participants
Region of Enrollment Taiwan	122 participants n=258 Participants	138 participants n=261 Participants	260 participants n=519 Participants
BMI	23.95 kg/m^2 STANDARD_DEVIATION 3.261 • n=258 Participants	23.74 kg/m^2 STANDARD_DEVIATION 3.015 • n=261 Participants	23.84 kg/m^2 STANDARD_DEVIATION 3.138 • n=519 Participants
Liver Cirrhosis (Pre-Operative) Missing	2 Participants n=258 Participants	6 Participants n=261 Participants	8 Participants n=519 Participants
Liver Cirrhosis (Pre-Operative) None	105 Participants n=258 Participants	94 Participants n=261 Participants	199 Participants n=519 Participants
Liver Cirrhosis (Pre-Operative) Mild	109 Participants n=258 Participants	130 Participants n=261 Participants	239 Participants n=519 Participants
Liver Cirrhosis (Pre-Operative) Moderate	35 Participants n=258 Participants	22 Participants n=261 Participants	57 Participants n=519 Participants
Liver Cirrhosis (Pre-Operative) Severe	7 Participants n=258 Participants	9 Participants n=261 Participants	16 Participants n=519 Participants
Total CLIP Score (categorized) Missing	1 units on a scale n=258 Participants	1 units on a scale n=261 Participants	2 units on a scale n=519 Participants
Total CLIP Score (categorized) 0	146 units on a scale n=258 Participants	171 units on a scale n=261 Participants	317 units on a scale n=519 Participants
Total CLIP Score (categorized) 1	83 units on a scale n=258 Participants	64 units on a scale n=261 Participants	147 units on a scale n=519 Participants
Total CLIP Score (categorized) 2	19 units on a scale n=258 Participants	19 units on a scale n=261 Participants	38 units on a scale n=519 Participants
Total CLIP Score (categorized) 3	7 units on a scale n=258 Participants	3 units on a scale n=261 Participants	10 units on a scale n=519 Participants
Total CLIP Score (categorized) 4	2 units on a scale n=258 Participants	3 units on a scale n=261 Participants	5 units on a scale n=519 Participants
Child-Pugh Stage Missing	1 units on a scale n=258 Participants	1 units on a scale n=261 Participants	2 units on a scale n=519 Participants
Child-Pugh Stage A (5 - 6 points)	256 units on a scale n=258 Participants	258 units on a scale n=261 Participants	514 units on a scale n=519 Participants
Child-Pugh Stage B (7 - 9 points)	1 units on a scale n=258 Participants	2 units on a scale n=261 Participants	3 units on a scale n=519 Participants
Tumor Morphology Missing	1 Participants n=258 Participants	1 Participants n=261 Participants	2 Participants n=519 Participants
Tumor Morphology Uninodular and extension <= 50%	213 Participants n=258 Participants	228 Participants n=261 Participants	441 Participants n=519 Participants
Tumor Morphology Multinodular and extension <= 50%	34 Participants n=258 Participants	28 Participants n=261 Participants	62 Participants n=519 Participants
Tumor Morphology Massive or extension > 50%	10 Participants n=258 Participants	4 Participants n=261 Participants	14 Participants n=519 Participants
AFP Missing	1 Participants n=258 Participants	1 Participants n=261 Participants	2 Participants n=519 Participants
AFP < 400 ng/ml	187 Participants n=258 Participants	197 Participants n=261 Participants	384 Participants n=519 Participants
AFP >= 400 ng/ml	70 Participants n=258 Participants	63 Participants n=261 Participants	133 Participants n=519 Participants
Portal Vein Thrombosis Missing	1 Participants n=258 Participants	1 Participants n=261 Participants	2 Participants n=519 Participants
Portal Vein Thrombosis No	234 Participants n=258 Participants	238 Participants n=261 Participants	472 Participants n=519 Participants
Portal Vein Thrombosis Yes	23 Participants n=258 Participants	22 Participants n=261 Participants	45 Participants n=519 Participants
ECOG Performance Score 0	245 Participants n=258 Participants	247 Participants n=261 Participants	492 Participants n=519 Participants
ECOG Performance Score 1	13 Participants n=258 Participants	14 Participants n=261 Participants	27 Participants n=519 Participants
Stratification V+L+	54 Participants n=258 Participants	53 Participants n=261 Participants	107 Participants n=519 Participants
Stratification V+L-	70 Participants n=258 Participants	74 Participants n=261 Participants	144 Participants n=519 Participants
Stratification V-L+	33 Participants n=258 Participants	36 Participants n=261 Participants	69 Participants n=519 Participants
Stratification V-L-	101 Participants n=258 Participants	98 Participants n=261 Participants	199 Participants n=519 Participants
Number of Tumors 1	223 Participants n=258 Participants	235 Participants n=261 Participants	458 Participants n=519 Participants
Number of Tumors 2	28 Participants n=258 Participants	20 Participants n=261 Participants	48 Participants n=519 Participants
Number of Tumors >=3	7 Participants n=258 Participants	6 Participants n=261 Participants	13 Participants n=519 Participants
Differentiation of Baseline Tumor Missing	1 Participants n=258 Participants	0 Participants n=261 Participants	1 Participants n=519 Participants
Differentiation of Baseline Tumor Well differentiated	13 Participants n=258 Participants	20 Participants n=261 Participants	33 Participants n=519 Participants
Differentiation of Baseline Tumor Moderately differentiated	143 Participants n=258 Participants	117 Participants n=261 Participants	260 Participants n=519 Participants
Differentiation of Baseline Tumor Poorly differentiated	86 Participants n=258 Participants	103 Participants n=261 Participants	189 Participants n=519 Participants
Differentiation of Baseline Tumor Anaplasia	15 Participants n=258 Participants	21 Participants n=261 Participants	36 Participants n=519 Participants
Size of the Largest Explanted Tumor <5 cm	171 Participants n=258 Participants	172 Participants n=261 Participants	343 Participants n=519 Participants
Size of the Largest Explanted Tumor 5 - <10 cm	63 Participants n=258 Participants	66 Participants n=261 Participants	129 Participants n=519 Participants
Size of the Largest Explanted Tumor >= 10 cm	24 Participants n=258 Participants	23 Participants n=261 Participants	47 Participants n=519 Participants
Surgical Margin of Explanted Tumor < 10 mm	118 Participants n=258 Participants	137 Participants n=261 Participants	255 Participants n=519 Participants
Surgical Margin of Explanted Tumor >= 10 mm	140 Participants n=258 Participants	123 Participants n=261 Participants	263 Participants n=519 Participants
Surgical Margin of Explanted Tumor NA	0 Participants n=258 Participants	1 Participants n=261 Participants	1 Participants n=519 Participants
Vascular Invasion Macro	18 Participants n=258 Participants	22 Participants n=261 Participants	40 Participants n=519 Participants
Vascular Invasion Micro Only	106 Participants n=258 Participants	105 Participants n=261 Participants	211 Participants n=519 Participants
Total Child-Pugh Score (categorized) 5	239 units on a scale n=258 Participants	242 units on a scale n=261 Participants	481 units on a scale n=519 Participants
Total Child-Pugh Score (categorized) 6	17 units on a scale n=258 Participants	16 units on a scale n=261 Participants	33 units on a scale n=519 Participants
Total Child-Pugh Score (categorized) 7	1 units on a scale n=258 Participants	1 units on a scale n=261 Participants	2 units on a scale n=519 Participants
Total Child-Pugh Score (categorized) 8	0 units on a scale n=258 Participants	1 units on a scale n=261 Participants	1 units on a scale n=519 Participants

PRIMARY outcome

Timeframe: End of study

Population: ITT population, defined as all subjects who were randomized.

Outcome measures

Outcome measures
Measure	PI-88 n=258 Participants Arm 1 PI-88: Lyophilized powder reconstituted to provide 160 mg of PI-88	Placebo n=261 Participants Arm 2 Placebo: Lactose lyophilized powder
Disease-Free Survival (DFS)	51.0 weeks Interval 28.0 to 52.7	75.6 weeks Interval 40.0 to 100.1

SECONDARY outcome

Timeframe: Time to recurrence (TTR) was defined as the time from randomization to the first time that tumor recurrence was observed or suspected during the study period (3 years).

Population: ITT population

As no subjects died without a preceding tumor recurrence , no median time to TTR could be estimated in the present study. And therefore the overall 25th percentile DFS was reported. The results of time to recurrence (TTR) were the same as that of DFS, as no subjects died without a preceding tumor recurrence.

Outcome measures

Outcome measures
Measure	PI-88 n=258 Participants Arm 1 PI-88: Lyophilized powder reconstituted to provide 160 mg of PI-88	Placebo n=261 Participants Arm 2 Placebo: Lactose lyophilized powder
Time to Recurrence (TTR)	51.0 weeks Interval 28.0 to 52.7	75.6 weeks Interval 40.0 to 100.1

SECONDARY outcome

Timeframe: Overall survival was defined as the time, in weeks, from randomization to death from any cause during the study period (3 years).

Population: ITT population

Overall survival was defined as the time, in weeks, from randomization to death from any cause during the study period.

Outcome measures

Outcome measures
Measure	PI-88 n=258 Participants Arm 1 PI-88: Lyophilized powder reconstituted to provide 160 mg of PI-88	Placebo n=261 Participants Arm 2 Placebo: Lactose lyophilized powder
Overall Survival (OS)	71.7 weeks Standard Error 0.37	69.2 weeks Standard Error 0.28

SECONDARY outcome

Timeframe: The cumulative tumor recurrence rate at weeks 5, 53, 101 and 149 was reported here.

Population: ITT population

TR rate was to calculate number of subjects with recurrence among the analyzed population.

Outcome measures

Outcome measures
Measure	PI-88 n=258 Participants Arm 1 PI-88: Lyophilized powder reconstituted to provide 160 mg of PI-88	Placebo n=261 Participants Arm 2 Placebo: Lactose lyophilized powder
Tumor Recurrence Rate (TR Rate) Cumulative Tumor Recurrence Rate at weeks 5	11 Participants	8 Participants
Tumor Recurrence Rate (TR Rate) Cumulative Tumor Recurrence Rate at weeks 53	74 Participants	58 Participants
Tumor Recurrence Rate (TR Rate) Cumulative Tumor Recurrence Rate at weeks 101	82 Participants	70 Participants
Tumor Recurrence Rate (TR Rate) Cumulative Tumor Recurrence Rate at weeks 149	85 Participants	74 Participants

Adverse Events

PI-88

Serious events: 30 serious events

Other events: 233 other events

Deaths: 0 deaths

Placebo

Serious events: 15 serious events

Other events: 201 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Clinical Research Manager

Medigen Biotechnology Corp.

Phone: 886-2-77361234

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	PI-88 n=258 participants at risk Arm 1 PI-88: Lyophilized powder reconstituted to provide 160 mg of PI-88 In the safety population, the subjects were analyzed according to the actual treatment received and must have received at least one dose of study medication. A total of 258 subjects were included in the safety population.	Placebo n=260 participants at risk Arm 2 Placebo: Lactose lyophilized powder In the safety population, the subjects were analyzed according to the actual treatment received and must have received at least one dose of study medication. Because one subject withdrew the consent before treatment, a total of 260 subjects were included in the safety population.
Skin and subcutaneous tissue disorders Alopecia	25.2% 65/258 • The adverse events were collected at each study visit during the study period (3 year). In the safety population, the subjects were analyzed according to the actual treatment received and must have received at least one dose of study medication.	2.7% 7/260 • The adverse events were collected at each study visit during the study period (3 year). In the safety population, the subjects were analyzed according to the actual treatment received and must have received at least one dose of study medication.
Investigations Platelet count decreased	15.5% 40/258 • The adverse events were collected at each study visit during the study period (3 year). In the safety population, the subjects were analyzed according to the actual treatment received and must have received at least one dose of study medication.	5.0% 13/260 • The adverse events were collected at each study visit during the study period (3 year). In the safety population, the subjects were analyzed according to the actual treatment received and must have received at least one dose of study medication.
General disorders Injection site haematoma	13.2% 34/258 • The adverse events were collected at each study visit during the study period (3 year). In the safety population, the subjects were analyzed according to the actual treatment received and must have received at least one dose of study medication.	2.7% 7/260 • The adverse events were collected at each study visit during the study period (3 year). In the safety population, the subjects were analyzed according to the actual treatment received and must have received at least one dose of study medication.
Infections and infestations Upper respiratory tract infection	12.8% 33/258 • The adverse events were collected at each study visit during the study period (3 year). In the safety population, the subjects were analyzed according to the actual treatment received and must have received at least one dose of study medication.	6.5% 17/260 • The adverse events were collected at each study visit during the study period (3 year). In the safety population, the subjects were analyzed according to the actual treatment received and must have received at least one dose of study medication.
Investigations Alanine aminotransferase increased	12.4% 32/258 • The adverse events were collected at each study visit during the study period (3 year). In the safety population, the subjects were analyzed according to the actual treatment received and must have received at least one dose of study medication.	8.8% 23/260 • The adverse events were collected at each study visit during the study period (3 year). In the safety population, the subjects were analyzed according to the actual treatment received and must have received at least one dose of study medication.
Skin and subcutaneous tissue disorders Pruritus	10.1% 26/258 • The adverse events were collected at each study visit during the study period (3 year). In the safety population, the subjects were analyzed according to the actual treatment received and must have received at least one dose of study medication.	7.3% 19/260 • The adverse events were collected at each study visit during the study period (3 year). In the safety population, the subjects were analyzed according to the actual treatment received and must have received at least one dose of study medication.
Investigations Aspartate aminotransferase increased	9.3% 24/258 • The adverse events were collected at each study visit during the study period (3 year). In the safety population, the subjects were analyzed according to the actual treatment received and must have received at least one dose of study medication.	8.1% 21/260 • The adverse events were collected at each study visit during the study period (3 year). In the safety population, the subjects were analyzed according to the actual treatment received and must have received at least one dose of study medication.
Gastrointestinal disorders Diarrhoea	9.3% 24/258 • The adverse events were collected at each study visit during the study period (3 year). In the safety population, the subjects were analyzed according to the actual treatment received and must have received at least one dose of study medication.	5.0% 13/260 • The adverse events were collected at each study visit during the study period (3 year). In the safety population, the subjects were analyzed according to the actual treatment received and must have received at least one dose of study medication.
Skin and subcutaneous tissue disorders Rash	9.3% 24/258 • The adverse events were collected at each study visit during the study period (3 year). In the safety population, the subjects were analyzed according to the actual treatment received and must have received at least one dose of study medication.	3.1% 8/260 • The adverse events were collected at each study visit during the study period (3 year). In the safety population, the subjects were analyzed according to the actual treatment received and must have received at least one dose of study medication.
Psychiatric disorders Insomnia	8.1% 21/258 • The adverse events were collected at each study visit during the study period (3 year). In the safety population, the subjects were analyzed according to the actual treatment received and must have received at least one dose of study medication.	10.4% 27/260 • The adverse events were collected at each study visit during the study period (3 year). In the safety population, the subjects were analyzed according to the actual treatment received and must have received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders Cough	7.4% 19/258 • The adverse events were collected at each study visit during the study period (3 year). In the safety population, the subjects were analyzed according to the actual treatment received and must have received at least one dose of study medication.	8.1% 21/260 • The adverse events were collected at each study visit during the study period (3 year). In the safety population, the subjects were analyzed according to the actual treatment received and must have received at least one dose of study medication.
Investigations Neutrophil count decreased	7.4% 19/258 • The adverse events were collected at each study visit during the study period (3 year). In the safety population, the subjects were analyzed according to the actual treatment received and must have received at least one dose of study medication.	1.2% 3/260 • The adverse events were collected at each study visit during the study period (3 year). In the safety population, the subjects were analyzed according to the actual treatment received and must have received at least one dose of study medication.
General disorders Injection site haemorrhage	7.0% 18/258 • The adverse events were collected at each study visit during the study period (3 year). In the safety population, the subjects were analyzed according to the actual treatment received and must have received at least one dose of study medication.	0.00% 0/260 • The adverse events were collected at each study visit during the study period (3 year). In the safety population, the subjects were analyzed according to the actual treatment received and must have received at least one dose of study medication.
Gastrointestinal disorders Abdominal pain upper	6.2% 16/258 • The adverse events were collected at each study visit during the study period (3 year). In the safety population, the subjects were analyzed according to the actual treatment received and must have received at least one dose of study medication.	4.6% 12/260 • The adverse events were collected at each study visit during the study period (3 year). In the safety population, the subjects were analyzed according to the actual treatment received and must have received at least one dose of study medication.
Investigations Alpha 1 foetoprotein increased	6.2% 16/258 • The adverse events were collected at each study visit during the study period (3 year). In the safety population, the subjects were analyzed according to the actual treatment received and must have received at least one dose of study medication.	3.5% 9/260 • The adverse events were collected at each study visit during the study period (3 year). In the safety population, the subjects were analyzed according to the actual treatment received and must have received at least one dose of study medication.
Nervous system disorders Dizziness	6.2% 16/258 • The adverse events were collected at each study visit during the study period (3 year). In the safety population, the subjects were analyzed according to the actual treatment received and must have received at least one dose of study medication.	5.4% 14/260 • The adverse events were collected at each study visit during the study period (3 year). In the safety population, the subjects were analyzed according to the actual treatment received and must have received at least one dose of study medication.
General disorders Fatigue	6.2% 16/258 • The adverse events were collected at each study visit during the study period (3 year). In the safety population, the subjects were analyzed according to the actual treatment received and must have received at least one dose of study medication.	5.0% 13/260 • The adverse events were collected at each study visit during the study period (3 year). In the safety population, the subjects were analyzed according to the actual treatment received and must have received at least one dose of study medication.
Musculoskeletal and connective tissue disorders Back pain	5.8% 15/258 • The adverse events were collected at each study visit during the study period (3 year). In the safety population, the subjects were analyzed according to the actual treatment received and must have received at least one dose of study medication.	5.4% 14/260 • The adverse events were collected at each study visit during the study period (3 year). In the safety population, the subjects were analyzed according to the actual treatment received and must have received at least one dose of study medication.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	5.4% 14/258 • The adverse events were collected at each study visit during the study period (3 year). In the safety population, the subjects were analyzed according to the actual treatment received and must have received at least one dose of study medication.	2.3% 6/260 • The adverse events were collected at each study visit during the study period (3 year). In the safety population, the subjects were analyzed according to the actual treatment received and must have received at least one dose of study medication.
General disorders Injection site pain	5.0% 13/258 • The adverse events were collected at each study visit during the study period (3 year). In the safety population, the subjects were analyzed according to the actual treatment received and must have received at least one dose of study medication.	0.77% 2/260 • The adverse events were collected at each study visit during the study period (3 year). In the safety population, the subjects were analyzed according to the actual treatment received and must have received at least one dose of study medication.
General disorders Injection site reaction	5.0% 13/258 • The adverse events were collected at each study visit during the study period (3 year). In the safety population, the subjects were analyzed according to the actual treatment received and must have received at least one dose of study medication.	1.2% 3/260 • The adverse events were collected at each study visit during the study period (3 year). In the safety population, the subjects were analyzed according to the actual treatment received and must have received at least one dose of study medication.