Clinical Trial Results:
A Phase 2, Double-Blind, Placebo Controlled Study of RV001V in Men with Biochemical Failure following Curatively Intended Therapy for Localized Prostate Cancer
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Summary
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EudraCT number |
2019-000951-14 |
Trial protocol |
DK FI SE DE BE GB |
Global end of trial date |
02 Jun 2022
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Results information
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Results version number |
v1(current) |
This version publication date |
06 Jan 2023
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First version publication date |
06 Jan 2023
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Other versions |
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Summary report(s) |
Abbreviated CSR_Synopsis |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
RhoVac-002
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03199872 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
RhoVac ApS
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Sponsor organisation address |
Agern Alle 24, Hørsholm, Denmark, 2970
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Public contact |
Malene Weis, RhoVac ApS, +45 53542818, mw@rhovac.com
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Scientific contact |
Malene Weis, RhoVac ApS, +45 53542818, mw@rhovac.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
18 Aug 2022
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
18 May 2022
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Global end of trial reached? |
Yes
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Global end of trial date |
02 Jun 2022
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The primary objective is to investigate whether a vaccination regimen with multiple subcutaneous (SC) administrations of RV001 Vaccine 0.1 mg/mL (RV001V) can reduce prostate-specific antigen (PSA) progression compared to the control group.
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Protection of trial subjects |
The DMC will be advisory to the Sponsor. The DMC will periodically monitor the accumulating data from the trial, including central
laboratory data, and advise the Sponsor regarding the continuing safety of trial subjects and thoseyet to be recruited to the trial, as well as the continuing validity. The primary charge of the DMC is to monitor the study for participant safety. DMC
responsibilities include;
- Protect the safety of the study participants;
- Review and evaluate ad hoc safety issues concerning the study at the request of
the sponsor;
- Make recommendations to the sponsor concerning continuation, termination, or
other modifications of the study based on the observed beneficial or adverse effects
of the study;
- Consider factors external to the study when relevant information becomes available,
such as scientific or therapeutic developments that may have an impact on
participant safety, scientific integrity, or the ethics of conducting the study
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 Jul 2019
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Sweden: 22
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Country: Number of subjects enrolled |
United Kingdom: 6
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Country: Number of subjects enrolled |
Belgium: 12
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Country: Number of subjects enrolled |
Denmark: 72
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Country: Number of subjects enrolled |
Finland: 22
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Country: Number of subjects enrolled |
Germany: 19
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Country: Number of subjects enrolled |
United States: 39
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Worldwide total number of subjects |
192
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EEA total number of subjects |
147
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
43
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From 65 to 84 years |
146
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85 years and over |
3
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Recruitment
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Recruitment details |
- | ||||||||||||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
Of the 257 subjects who signed the written informed consent form (IC), 192 subjects completed the screening and were enrolled in the study. For the 65 patients who were not eligible for participation, the major reason was BCR after the last definitive treatment, distant metastasis or locoregional recurrence. | ||||||||||||||||||||||||||||||||||||
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Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator | ||||||||||||||||||||||||||||||||||||
Blinding implementation details |
Investigators, patients, and all study staff with direct patient contact were blinded to assignment to RV001V or placebo. The Interactive web response system IWRS assigned RV001V, or placebo based on a block randomization scheme.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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RV001V group | ||||||||||||||||||||||||||||||||||||
Arm description |
RV001 vaccine 0.1 mg/mL in water-in-oil (w/o) emulsion for injection containing RV001 and the adjuvant Montanide ISA 51 were administered to subjects in the V001V arm at a dose of 0.1 mg RV001 | ||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
RV001
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
The dose of RV001 0.1 mg was given as a subcutaneous injection
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Arm title
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Placebo | ||||||||||||||||||||||||||||||||||||
Arm description |
Placebo vaccine containing 50/50 mixture of adjuvant and sterile acetate buffered saline pH 3.5 in a 1-mL syringe | ||||||||||||||||||||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo vaccine
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Placebo vaccine containing 50/50 mixture of adjuvant and sterile acetate buffered saline pH 3.5 in a 1-mL syringe
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Baseline characteristics reporting groups
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Reporting group title |
Overall trial
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Reporting group description |
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Subject analysis sets
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Subject analysis set title |
Primary Analysis
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Subject analysis set type |
Modified intention-to-treat | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Strata combined and based on the primary analysis which were conducted when 88 events had occurred in the modified intention-to-treat (m-ITT) population
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End points reporting groups
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Reporting group title |
RV001V group
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Reporting group description |
RV001 vaccine 0.1 mg/mL in water-in-oil (w/o) emulsion for injection containing RV001 and the adjuvant Montanide ISA 51 were administered to subjects in the V001V arm at a dose of 0.1 mg RV001 | ||
Reporting group title |
Placebo
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Reporting group description |
Placebo vaccine containing 50/50 mixture of adjuvant and sterile acetate buffered saline pH 3.5 in a 1-mL syringe | ||
Subject analysis set title |
Primary Analysis
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Subject analysis set type |
Modified intention-to-treat | ||
Subject analysis set description |
Strata combined and based on the primary analysis which were conducted when 88 events had occurred in the modified intention-to-treat (m-ITT) population
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End point title |
Primary endpoint | |||||||||||||||
End point description |
The primary endpoint was defined as the time from randomization until doubling of PSA from the baseline value, clinical recurrence or death from any cause, whichever occurred first. When the subject reached a primary endpoint, he continued into the extended follow up (E-FU) phase for safety monitoring until the study was terminated 36 months after first subject’s first injection. At the time of the primary analysis all subjects who have not yet reached the primary endpoint continued into E-FU for safety until study termination.
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End point type |
Primary
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End point timeframe |
The primary endpoint was defined as the time from randomization until doubling of PSA from the baseline value
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Statistical analysis title |
Cox regression analysis | |||||||||||||||
Comparison groups |
RV001V group v Placebo
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Number of subjects included in analysis |
185
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Analysis specification |
Pre-specified
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Analysis type |
equivalence | |||||||||||||||
P-value |
= 0.1327 | |||||||||||||||
Method |
Regression, Cox | |||||||||||||||
Parameter type |
Hazard ratio (HR) | |||||||||||||||
Confidence interval |
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95% | |||||||||||||||
sides |
2-sided
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lower limit |
0.91 | |||||||||||||||
upper limit |
2.07 | |||||||||||||||
Variability estimate |
Standard deviation
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Dispersion value |
1.37
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Adverse events information
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Timeframe for reporting adverse events |
Overall study period
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
25.0
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Reporting groups
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Reporting group title |
Safety population
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Reporting group description |
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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12 Apr 2019 |
Revision of protocol from V1.0 to V2.0
- Front page: Short protocol name BRaVac is added to front page
- Section 2.3 and 7.7.2: Exploratory endpoint C removed from protocol.
- Section 6.1: Collection of archival tumor slice has been removed from the protocol. This relates to the above reasons re. the exploratory endpoint.
- Section 6.1: Collection of oncology history including oncotype DX and radiation dose, in case the patient has received radiation therapy as part of previous curative treatment, has been added. This is based on recommendation from FDA received at a recent pre-IND meeting.
- Section 7.3 and 9.1.1: Specification of collection of AEs/SAEs during follow up and E-follow up. AEs/SAEs are collected for 3 months post End of Treatment visit.
- Section 9.11.1: Description of Dose Limiting Toxicities (DLTs) has been removed.
- Section 13.1: Precision of what can be considered source document in accordance with GCP.
- Section 14: Change in the publication strategy rec |
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15 May 2019 |
Protocol V2.0 to V3.0
- Synopsis: number of sites reduced from 35 to 30
- Section 4.3; Selection/Enrollment of Patients; Amended to clarify that only inclusion/exclusion
data relevant to randomsiation in IWRS will be entered in IWRS
- Section 5.6 Blinding and Unblinding Method; updated to clarify that the investigator can unblind a
patient with our first speaking to the Medical Monitor. Where possible the Medical monitor should
be consulted.
- Section 9.1.1 AE Monitoring: updated to clarify that any untoward medical occurrence event that
occurs after screening and before the first dose of IP will be recorded as a S(AE)
- Section 9.1.2 Reporting of Adverse Events; the following text was added;
- Section 9.2.1 Adverse Events; clarification that surgical procedure (pre-planned) is not
considered an AE
- 9.8 Reporting Serious Adverse Events, the following sentence was deleted; |
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13 Nov 2019 |
Protocol V3.0 to V4.0
- Specification of primary end point further with method for calculating PSA doubling
- Slight revision of secondary and exploratory endpoint
- Adaption of inclusion criteria
- Adaption of exclusion criteria
- Adding a specific benefit-risk assessment section
- Safety monitorin process updated
- DMC section updated
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08 Jul 2020 |
Protocol V4.0 to V4.0 with Amendment #1
- Removal of Gleason score from study inclusion criteria and enrolment of
patients based on PSA doubling time, to allow for inclusion of additional
patients potentially benefitting from treatment
- Collection of highest historical Gleason score at baseline for each patient added
to assessments and procedures |
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26 Mar 2021 |
Protocol V4.0 with Amendment #1 to V4.0 with Amendments #1 and #2
- Correction of incorrect hemoglobin value
- COVID-19 vaccination allowed during RV001 priming and maintenance
treatment periods with down to 6 days following each injection
- COVID-19 vaccination excluded from prohibited medications
- Rewording to remove unnecessary restriction of standard diagnositcs in
tumor assessments
- Deletion of Annex 1: Gleason Score, as no longer applicable following
amendment #1 to v4.0 |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
