Clinical Trial Results:
A Single Blind, Two-Stage Dose Finding Study to Evaluate the Safety, Tolerability and Efficacy of a Single Liproca® Depot Injection into the Prostate in Patients with Localized Prostate Cancer, Assigned to Active Surveillance who are at High Risk for Disease Progression (followed by an Open Label Extension with a Repeat Injection (Optional)).

Trial information Top of page
Trial identification
Sponsor protocol code	LPC-004
Additional study identifiers
ISRCTN number	-
US NCT number	NCT03348527
WHO universal trial number (UTN)	-
Sponsors
Sponsor organisation name	LIDDS AB
Sponsor organisation address	Virdings Alle 32b, Uppsala, Sweden, SE-75450
Public contact	Nina Herne, LIDDS AB, nina.herne@liddspharma.com
Scientific contact	Charlotta Gauffin, LIDDS AB, charlotta.gauffin@liddspharma.com
Paediatric regulatory details
Is trial part of an agreed paediatric investigation plan (PIP)	No
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?	No
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?	No
Results analysis stage
Analysis stage	Final
Date of interim/final analysis	26 Aug 2020
Is this the analysis of the primary completion data?	No
Global end of trial reached?	Yes
Global end of trial date	06 Jul 2020
Was the trial ended prematurely?	No
General information about the trial
Main objective of the trial	Primary objectives: •To define the highest tolerable dose of Liproca®Depot for transrectal injection into the prostate •To determine the level of Prostate Specific Antigen (PSA) reduction for the doses in Treatment groups 3 and 4
Protection of trial subjects	Patients received prophylactic antibiotics prior to transrectal injection procedure.
Background therapy	-
Evidence for comparator	-
Actual start date of recruitment	26 Jun 2017
Long term follow-up planned	No
Independent data monitoring committee (IDMC) involvement?	Yes
Population of trial subjects
Number of subjects enrolled per country
Country: Number of subjects enrolled	Finland: 3
Country: Number of subjects enrolled	Lithuania: 24
Country: Number of subjects enrolled	Canada: 34
Worldwide total number of subjects	61
EEA total number of subjects	27
Number of subjects enrolled per age group
In utero	0
Preterm newborn - gestational age < 37 wk	0
Newborns (0-27 days)	0
Infants and toddlers (28 days-23 months)	0
Children (2-11 years)	0
Adolescents (12-17 years)	0
Adults (18-64 years)	37
From 65 to 84 years	24
85 years and over	0

Trial information Top of page

Subject disposition Top of page
Recruitment
Recruitment details	First patient in: 26 June 2017. Last patient out: 06 July 2020
Pre-assignment
Screening details	Men at 18 - 80 years of age and assigned to Active Surveillance Histologically confirmed, localized prostate cancer with Gleason score 3+3 or 3+4 . PSA must be below 20 ng/mL. No previous or ongoing hormonal therapy for prostate cancer allowed.
Period 1
Period 1 title	Single dose
Is this the baseline period?	Yes
Allocation method	Not applicable
Blinding used	Not blinded
Arms
Are arms mutually exclusive	Yes
Arm title	Treatment group 1
Arm description	Dose: 35% of prostate volume
Arm type	Experimental
Investigational medicinal product name	Liproca Depot
Investigational medicinal product code
Other name
Pharmaceutical forms	Concentrate and solvent for suspension for injection
Routes of administration	Injection
Dosage and administration details	Single dose, injection at baseline. Intraprostatic injection of suspension.
Arm title	Treatment group 2
Arm description	Dose: 45% of prostate volume
Arm type	Experimental
Investigational medicinal product name	Liproca Depot
Investigational medicinal product code
Other name
Pharmaceutical forms	Concentrate and solvent for suspension for injection
Routes of administration	Injection
Dosage and administration details	Single dose, injection at baseline. Intraprostatic injection of suspension.
Arm title	Treatment group 3
Arm description	Dose: 16 mL
Arm type	Experimental
Investigational medicinal product name	Liproca Depot
Investigational medicinal product code
Other name
Pharmaceutical forms	Concentrate and solvent for suspension for injection
Routes of administration	Injection
Dosage and administration details	Single dose, injection at baseline. Intraprostatic injection of suspension.
Arm title	Treatment group 4
Arm description	Dose: 20 mL
Arm type	Experimental
Investigational medicinal product name	Liproca Depot
Investigational medicinal product code
Other name
Pharmaceutical forms	Concentrate and solvent for suspension for injection
Routes of administration	Injection
Dosage and administration details	Single dose, injection at baseline. Intraprostatic injection of suspension.
Number of subjects in period 1 Treatment group 1 Treatment group 2 Treatment group 3 Treatment group 4 Started 10 10 21 20 Completed 10 10 21 20
Period 2
Period 2 title	Repeat dose
Is this the baseline period?	No
Allocation method	Not applicable
Blinding used	Not blinded
Arms
Arm title	Repeated dose
Arm description	Repeted injection of study drug
Arm type	Experimental
Investigational medicinal product name	Liproca Depot
Investigational medicinal product code
Other name
Pharmaceutical forms	Concentrate and solvent for suspension for injection
Routes of administration	Injection
Dosage and administration details	Repeted injection of study drug. Intraprostatic injection of suspension.
Number of subjects in period 2 [1] Repeated dose Started 12 Completed 12
Notes [1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period. Justification: Participation in Period 2 was voluntary

Subject disposition Top of page

Baseline characteristics Top of page
Baseline characteristics reporting groups
Reporting group title	Treatment group 1
Reporting group description	Dose: 35% of prostate volume
Reporting group title	Treatment group 2
Reporting group description	Dose: 45% of prostate volume
Reporting group title	Treatment group 3
Reporting group description	Dose: 16 mL
Reporting group title	Treatment group 4
Reporting group description	Dose: 20 mL
Reporting group values Treatment group 1 Treatment group 2 Treatment group 3 Treatment group 4 Total Number of subjects 10 10 21 20 61 Age categorical Units: Subjects     In utero 0 0 0 0 0     Preterm newborn infants (gestational age < 37 wks) 0 0 0 0 0     Newborns (0-27 days) 0 0 0 0 0     Infants and toddlers (28 days-23 months) 0 0 0 0 0     Children (2-11 years) 0 0 0 0 0     Adolescents (12-17 years) 0 0 0 0 0     Adults (18-64 years) 7 7 9 14 37     From 65-84 years 3 3 12 6 24     85 years and over 0 0 0 0 0 Gender categorical Units: Subjects     Female 0 0 0 0 0     Male 10 10 21 20 61

Baseline characteristics Top of page

End points Top of page
End points reporting groups
Reporting group title	Treatment group 1
Reporting group description	Dose: 35% of prostate volume
Reporting group title	Treatment group 2
Reporting group description	Dose: 45% of prostate volume
Reporting group title	Treatment group 3
Reporting group description	Dose: 16 mL
Reporting group title	Treatment group 4
Reporting group description	Dose: 20 mL
Reporting group title	Repeated dose
Reporting group description	Repeted injection of study drug

End points Top of page

Primary: PSA responder rate Top of page
End point title	PSA responder rate [1] [2]
End point description
End point type	Primary
End point timeframe	Week 20
Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Descriptive statistics. [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: All four arms were evaluated for safety, while only two arms were evaluated for efficacy in the primary objective and endpoint.
End point values Treatment group 3 Treatment group 4 Number of subjects analysed 21 20 Units: Percentage 57 40
No statistical analyses for this end point

Primary: PSA responder rate Top of page

Primary: Time to PSA recurrence Top of page
End point title	Time to PSA recurrence [3]
End point description
End point type	Primary
End point timeframe	24-48 weeks
Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Descriptive statistics.
End point values Repeated dose Number of subjects analysed 12 Units: week     arithmetic mean (full range (min-max)) 43 (32 to 48)
No statistical analyses for this end point

Primary: Time to PSA recurrence Top of page

Adverse events Top of page
Adverse events information
Timeframe for reporting adverse events	24 weeks
Assessment type	Systematic
Dictionary used for adverse event reporting
Dictionary name	MedDRA
Dictionary version	19.1
Reporting groups
Reporting group title	Treatment group 1
Reporting group description	-
Reporting group title	Treatment group 2
Reporting group description	-
Reporting group title	Treatment group 3
Reporting group description	-
Reporting group title	Treatment group 4
Reporting group description	-
Reporting group title	Repeated dose
Reporting group description	Repeated dose
Serious adverse events Treatment group 1 Treatment group 2 Treatment group 3 Treatment group 4 Repeated dose Total subjects affected by serious adverse events      subjects affected / exposed 1 / 10 (10.00%) 0 / 10 (0.00%) 1 / 21 (4.76%) 3 / 20 (15.00%) 1 / 6 (16.67%)      number of deaths (all causes) 0 0 0 0 0      number of deaths resulting from adverse events 0 0 0 0 0 Reproductive system and breast disorders Prostatitis      subjects affected / exposed 0 / 10 (0.00%) 0 / 10 (0.00%) 0 / 21 (0.00%) 2 / 20 (10.00%) 0 / 6 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 2 / 2 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Renal and urinary disorders Urinary retention      subjects affected / exposed 0 / 10 (0.00%) 0 / 10 (0.00%) 0 / 21 (0.00%) 0 / 20 (0.00%) 1 / 6 (16.67%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 1 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Infections and infestations Bacteraemia      subjects affected / exposed 1 / 10 (10.00%) 0 / 10 (0.00%) 0 / 21 (0.00%) 0 / 20 (0.00%) 0 / 6 (0.00%)      occurrences causally related to treatment / all 1 / 1 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Urosepsis      subjects affected / exposed 1 / 10 (10.00%) 0 / 10 (0.00%) 0 / 21 (0.00%) 0 / 20 (0.00%) 0 / 6 (0.00%)      occurrences causally related to treatment / all 1 / 1 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Appendicitis      subjects affected / exposed 0 / 10 (0.00%) 0 / 10 (0.00%) 1 / 21 (4.76%) 0 / 20 (0.00%) 0 / 6 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 1 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Sepsis      subjects affected / exposed 0 / 10 (0.00%) 0 / 10 (0.00%) 0 / 21 (0.00%) 1 / 20 (5.00%) 0 / 6 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 1 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0
Frequency threshold for reporting non-serious adverse events: 5%
Non-serious adverse events Treatment group 1 Treatment group 2 Treatment group 3 Treatment group 4 Repeated dose Total subjects affected by non serious adverse events      subjects affected / exposed 6 / 10 (60.00%) 5 / 10 (50.00%) 16 / 21 (76.19%) 15 / 20 (75.00%) 6 / 6 (100.00%) Investigations Blood urine present      subjects affected / exposed 0 / 10 (0.00%) 1 / 10 (10.00%) 1 / 21 (4.76%) 1 / 20 (5.00%) 1 / 6 (16.67%)      occurrences all number 0 1 1 1 1 Hepatic enzyme increased      subjects affected / exposed 0 / 10 (0.00%) 0 / 10 (0.00%) 0 / 21 (0.00%) 1 / 20 (5.00%) 0 / 6 (0.00%)      occurrences all number 0 0 0 1 0 C-reactive protein increased      subjects affected / exposed 0 / 10 (0.00%) 0 / 10 (0.00%) 1 / 21 (4.76%) 0 / 20 (0.00%) 0 / 6 (0.00%)      occurrences all number 0 0 1 0 0 Blood alkaline phosphatase increased      subjects affected / exposed 0 / 10 (0.00%) 0 / 10 (0.00%) 0 / 21 (0.00%) 1 / 20 (5.00%) 0 / 6 (0.00%)      occurrences all number 0 0 0 1 0 Alanine aminotransferase increased      subjects affected / exposed 0 / 10 (0.00%) 0 / 10 (0.00%) 0 / 21 (0.00%) 1 / 20 (5.00%) 0 / 6 (0.00%)      occurrences all number 0 0 0 1 0 Aspartate aminotransferase increased      subjects affected / exposed 0 / 10 (0.00%) 0 / 10 (0.00%) 0 / 21 (0.00%) 1 / 20 (5.00%) 0 / 6 (0.00%)      occurrences all number 0 0 0 1 0 General disorders and administration site conditions Pyrexia      subjects affected / exposed 1 / 10 (10.00%) 0 / 10 (0.00%) 2 / 21 (9.52%) 1 / 20 (5.00%) 1 / 6 (16.67%)      occurrences all number 1 0 2 1 1 Constipation      subjects affected / exposed 0 / 10 (0.00%) 1 / 10 (10.00%) 0 / 21 (0.00%) 0 / 20 (0.00%) 1 / 6 (16.67%)      occurrences all number 0 1 0 0 1 Injection site pain      subjects affected / exposed 0 / 10 (0.00%) 1 / 10 (10.00%) 0 / 21 (0.00%) 0 / 20 (0.00%) 0 / 6 (0.00%)      occurrences all number 0 1 0 0 0 Chills      subjects affected / exposed 0 / 10 (0.00%) 0 / 10 (0.00%) 1 / 21 (4.76%) 2 / 20 (10.00%) 1 / 6 (16.67%)      occurrences all number 0 0 1 2 1 Reproductive system and breast disorders Prostatitis      subjects affected / exposed 0 / 10 (0.00%) 0 / 10 (0.00%) 2 / 21 (9.52%) 2 / 20 (10.00%) 1 / 6 (16.67%)      occurrences all number 0 0 2 2 1 Prostatic pain      subjects affected / exposed 1 / 10 (10.00%) 0 / 10 (0.00%) 0 / 21 (0.00%) 0 / 20 (0.00%) 0 / 6 (0.00%)      occurrences all number 1 0 0 0 0 Gastrointestinal disorders Vomiting      subjects affected / exposed 1 / 10 (10.00%) 0 / 10 (0.00%) 0 / 21 (0.00%) 0 / 20 (0.00%) 0 / 6 (0.00%)      occurrences all number 1 0 0 0 0 Dyschezia      subjects affected / exposed 0 / 10 (0.00%) 0 / 10 (0.00%) 0 / 21 (0.00%) 2 / 20 (10.00%) 0 / 6 (0.00%)      occurrences all number 0 0 0 2 0 Haematochezia      subjects affected / exposed 0 / 10 (0.00%) 0 / 10 (0.00%) 0 / 21 (0.00%) 1 / 20 (5.00%) 0 / 6 (0.00%)      occurrences all number 0 0 0 1 0 Abdominal pain lower      subjects affected / exposed 0 / 10 (0.00%) 0 / 10 (0.00%) 0 / 21 (0.00%) 1 / 20 (5.00%) 1 / 6 (16.67%)      occurrences all number 0 0 0 1 1 Renal and urinary disorders Dysuria      subjects affected / exposed 1 / 10 (10.00%) 2 / 10 (20.00%) 5 / 21 (23.81%) 5 / 20 (25.00%) 1 / 6 (16.67%)      occurrences all number 1 3 6 5 2 Urinary retention      subjects affected / exposed 3 / 10 (30.00%) 2 / 10 (20.00%) 3 / 21 (14.29%) 5 / 20 (25.00%) 2 / 6 (33.33%)      occurrences all number 3 2 4 5 3 Haematuria      subjects affected / exposed 0 / 10 (0.00%) 0 / 10 (0.00%) 5 / 21 (23.81%) 5 / 20 (25.00%) 1 / 6 (16.67%)      occurrences all number 0 0 6 5 2 Hypertonic bladder      subjects affected / exposed 1 / 10 (10.00%) 0 / 10 (0.00%) 0 / 21 (0.00%) 0 / 20 (0.00%) 0 / 6 (0.00%)      occurrences all number 1 0 0 0 0 Micturition urgency      subjects affected / exposed 0 / 10 (0.00%) 1 / 10 (10.00%) 0 / 21 (0.00%) 1 / 20 (5.00%) 0 / 6 (0.00%)      occurrences all number 0 1 0 1 0 Pollakiuria      subjects affected / exposed 0 / 10 (0.00%) 1 / 10 (10.00%) 1 / 21 (4.76%) 2 / 20 (10.00%) 0 / 6 (0.00%)      occurrences all number 0 1 1 2 0 Nocturia      subjects affected / exposed 1 / 10 (10.00%) 0 / 10 (0.00%) 2 / 21 (9.52%) 0 / 20 (0.00%) 1 / 6 (16.67%)      occurrences all number 2 0 2 0 2 Lower urinary tract symptoms      subjects affected / exposed 0 / 10 (0.00%) 0 / 10 (0.00%) 3 / 21 (14.29%) 0 / 20 (0.00%) 0 / 6 (0.00%)      occurrences all number 0 0 3 0 0 Urine flow decreased      subjects affected / exposed 0 / 10 (0.00%) 0 / 10 (0.00%) 2 / 21 (9.52%) 1 / 20 (5.00%) 0 / 6 (0.00%)      occurrences all number 0 0 2 1 0 Leukocyturia      subjects affected / exposed 0 / 10 (0.00%) 0 / 10 (0.00%) 1 / 21 (4.76%) 1 / 20 (5.00%) 0 / 6 (0.00%)      occurrences all number 0 0 1 1 0 Infections and infestations Epididymitis      subjects affected / exposed 1 / 10 (10.00%) 0 / 10 (0.00%) 0 / 21 (0.00%) 0 / 20 (0.00%) 0 / 6 (0.00%)      occurrences all number 1 0 0 0 0 Metabolism and nutrition disorders Hyponatraemia      subjects affected / exposed 1 / 10 (10.00%) 0 / 10 (0.00%) 0 / 21 (0.00%) 0 / 20 (0.00%) 0 / 6 (0.00%)      occurrences all number 1 0 0 0 0 Hypokalaemia      subjects affected / exposed 1 / 10 (10.00%) 0 / 10 (0.00%) 0 / 21 (0.00%) 0 / 20 (0.00%) 0 / 6 (0.00%)      occurrences all number 1 0 0 0 0

Adverse events Top of page

More information Top of page
Substantial protocol amendments (globally)
Were there any global substantial amendments to the protocol? Yes
Date	Amendment
09 Mar 2017	Upon request from Health Canada: I/E criteria clarified, increased number of MRI assessments.
19 Jul 2017	Upon request by Health Canada: I/E criteria #9: Creatinine less than 30 times ULN changed to eGF equal or more than 30 mL/min (by Cockcroft-Gault)
11 Jun 2018	Following data safety monitoring board outcome: Change in injection procedure and dose levels for treatment arms 3 and 4.
06 Oct 2019	Upon Health Canada Request: Change in cut-off level for PSA-responder
Interruptions (globally)
Were there any global interruptions to the trial? No
Limitations and caveats
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
None reported
Online references
http://www.ncbi.nlm.nih.gov/pubmed/33583762

More information Top of page