Clinical Trial Results:
Phase III, open-label, multi-center study to assess the pharmacodynamic (PD), pharmacokinetic (PK) and safety of Zoreline 10.8 mg goserelin subcutaneous implant (Novalon) in male subjects with prostate cancer.
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Summary
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EudraCT number |
2019-000593-32 |
Trial protocol |
DE |
Global end of trial date |
06 Apr 2020
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Results information
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Results version number |
v1(current) |
This version publication date |
16 May 2021
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First version publication date |
16 May 2021
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Other versions |
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Summary report(s) |
Synopsis CSR |
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 |
MIT-Zo002-C301
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Additional study identifiers
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ISRCTN number |
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US NCT number |
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WHO universal trial number (UTN) |
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Sponsors
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Sponsor organisation name |
Novalon S.A
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Sponsor organisation address |
Rue Saint-Georges 5-7, Liege, Belgium, 4000
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Public contact |
Mithra Pharmaceuticals SA Pharma Department, Mithra Pharmaceuticals, Novalon S.A, +32 43492822, clinicaltrials@mithra.com
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Scientific contact |
Mithra Pharmaceuticals SA Pharma Department, Mithra Pharmaceuticals, Novalon S.A, +32 43492822, clinicaltrials@mithra.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 |
02 Feb 2021
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
06 Apr 2020
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
To assess the ability of Zoreline 10.8 mg subcutaneous implant to induce testosterone serum suppression (≤50 ng/dL) in male subjects with prostate cancer by Day 29 of Cycle 1 at the latest and have this confirmed at Day 85 of Cycle 1 and Day 85 of Cycle 2 (End of Treatment)
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Protection of trial subjects |
Subjects had to abstain from the use of all concomitant medications as described in the exclusion criteria: GnRH agonist or antagonist therapy, and any treatment that interferes with testosterone serum level. Previous and concomitant treatment with GnRH analogs was not allowed. However, subjects who previously underwent an intermittent treatment scheme could be included if no more than two treatment cycles were received and if the last treatment injection was not within 6 months of the screening visit (as per eligibility criteria). A treatment cycle was defined as the continuous and repeated administration of a GnRH analog (according to the prescribing information) until discontinuation of treatment based on the subject’s physical and / or disease status as judged by the Investigator. Non-steroidal anti-androgens (such as bicalutamide, flutamide, nilutamide, enzalutamide) were allowed to prevent disease flare-ups only, caused by testosterone surges. Treatment with non-steroidal anti-androgens was at the discretion of the Investigator. Further occurrence of disease flare-ups caused by testosterone surges had to be treated symptomatically as determined by the Investigator. The following rules had to be taken into account when prescribing other treatments during the subject’s participation in the trial:
•Ancillary treatments were allowed to be given as medically indicated; they should have been recorded in the subjects’ medical chart and on the appropriate electronic Case Report Form (eCRF);
•Radiotherapy was allowed to be given concomitantly for control of bone pain or other reasons;
•Subjects were not allowed to receive other anticancer treatments or other investigational agents from start of trial treatment until the End of Treatment visit;
•In case of doubt, concomitant medication could be discussed with the Medical Monitor.
The use of local anesthetic was allowed if this was part of local practice
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Background therapy |
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Evidence for comparator |
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Actual start date of recruitment |
14 Jun 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 |
Moldova, Republic of: 40
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Country: Number of subjects enrolled |
Georgia: 13
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Country: Number of subjects enrolled |
Ukraine: 31
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Country: Number of subjects enrolled |
Germany: 58
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Worldwide total number of subjects |
142
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EEA total number of subjects |
58
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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) |
32
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From 65 to 84 years |
105
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85 years and over |
5
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Recruitment
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Recruitment details |
In 14 trial sites in Germany, Moldova, Georgia and Ukraine, the trial subjects were recruited. In total 142 subjects meeting all eligibility criteria were enrolled. The first patient was included on 14Jun2019. Last study visit before database lock was 06Apr2020. | ||||||||||||
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Pre-assignment
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Screening details |
Male subjects (>18 years old) with prostate cancer. 169 subjects were screened and signed the ICF with 142 meeting all eligibility criteria and starting treatment with Zoreline. A total of 24 subjects were part of the pharmacokinetic sub-study. Each enrolled subject received the 10.8 mg goserelin (Zoreline) SC implant | ||||||||||||
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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 |
Not applicable
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Blinding used |
Not blinded | ||||||||||||
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Arms
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Arm title
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Each enrolled subject received 10.8 mg Zoreline SC implant | ||||||||||||
Arm description |
142 subjects started the treatment with Zoreline. The subjects had to come to the clinic center on Days 1, 2, 4, 8, 15, 29, 30, 36, 57, 84, and on Day 85 of Cycle 1 (=pre-dose on Day 1 of Cycle 2) and on Days 2, 4, 8, 15, 29, 36, 57, 84, and on Day 85 of Cycle 2 (which is the End of Treatment day). A total of 24 subjects were part of the pharmacokinetic (PK) substudy. This group had additional blood samples taken to assess the PK profile of the trial medication in addition to their blood collected for pharmacodynamic and safety assessments. Subjects in the PK substudy had seven additional visits on Days 22, 43, 45, 50, 64, 71 and 78 of Cycle 1. After all the PK substudy was not performed: the study was terminated early because of efficacy risks and the PK parameters were not evaluated because no PK analysis was performed on the respective samples. Each treatment cycle had a duration of 84 days. The total treatment duration of this trial was 168 days, two cycles. | ||||||||||||
Arm type |
Experimental | ||||||||||||
Investigational medicinal product name |
Zoreline
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Implant in pre-filled syringe
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
10.8 mg depot of Zoreline was injected subcutaneously into the anterior abdominal wall, every 84 days (12 weeks) on Day 1 of Cycle 1 and Day 1 of Cycle 2 (corresponding to Day 85 of Cycle 1).
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Baseline characteristics reporting groups
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Reporting group title |
Overall trial
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Reporting group description |
Overall, 169 subjects were screened and signed the ICF to participate in the trial (defined in this trial as the ENR population). Of these, 142 subjects were confirmed eligible on Cycle 1 Day 1, were enrolled in the trial and received at least one dose of trial medication (SAF population). The remainder of 27 subjects did not meet all eligibility criteria and were considered screen failures. ITT population was identical to SAF population. The Per Protocol population consisted of 31 subjects of the ITT population who completed the study. The study was terminated early because of efficacy risks and the PK parameters planned to be assessed in samples taken from the PK subset were not evaluated because no PK analysis was performed on the respective samples. Screened population (and who signed the ICF): 169 Safety set (SAF) population: 142 Intent-to-treat set (ITT) population: 142 Per Protocol set (PP) population: 31 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Each enrolled subject received 10.8 mg Zoreline SC implant
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Reporting group description |
142 subjects started the treatment with Zoreline. The subjects had to come to the clinic center on Days 1, 2, 4, 8, 15, 29, 30, 36, 57, 84, and on Day 85 of Cycle 1 (=pre-dose on Day 1 of Cycle 2) and on Days 2, 4, 8, 15, 29, 36, 57, 84, and on Day 85 of Cycle 2 (which is the End of Treatment day). A total of 24 subjects were part of the pharmacokinetic (PK) substudy. This group had additional blood samples taken to assess the PK profile of the trial medication in addition to their blood collected for pharmacodynamic and safety assessments. Subjects in the PK substudy had seven additional visits on Days 22, 43, 45, 50, 64, 71 and 78 of Cycle 1. After all the PK substudy was not performed: the study was terminated early because of efficacy risks and the PK parameters were not evaluated because no PK analysis was performed on the respective samples. Each treatment cycle had a duration of 84 days. The total treatment duration of this trial was 168 days, two cycles. | ||
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End point title |
Pharmacodynamics [1] | ||||||||||
End point description |
Responder subjects are subjects for which a response was defined as the subject having serum testosterone levels ≤50 ng/dL on at least one of the sampling time points on consecutive days. This assessment was done on the Intention to Treat Population.
The following values list the responder subjects of the ITT population N=142
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End point type |
Primary
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End point timeframe |
Cycle 1 Day 29 or 30; Cycle 1 Day 84 or Day 85; Cycle 2 Day 84 or 85
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| 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: Testosterone levels were planned to be determined for each subject from D1 of Cycle 1 to D85 of Cycle 2 (End of Treatment). Due to early termination of the trial, testosterone levels were evaluated for 42 subjects up to D85 of Cycle 1. The response rates are listed per time-point together with a 95% 2-sided CI (exact method). |
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| No statistical analyses for this end point | |||||||||||
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End point title |
Pharmacodynamics | ||||||||||||||||||||||||||
End point description |
Serum concentrations of testosterone.
Because of the early termination of the trial, no further planned efficacy, PK, and pharmacodynamic evaluations analysis were performed.
In the following section the median value for the change from baseline visit were added from the Intention to Treat population is listed.
With the between brackets the mimimum and maximum value
Med (Min to Max)
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End point type |
Secondary
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End point timeframe |
Between D 1 and D 29 of Cycle 1,surge at re-injection and potential escape (surge) following the onset of suppression after the initial surge in Cycle 1 to Day 85 of Cycle 1 (pre-dose of Cycle 2) and after the surge at reinjection in Cycle 2 to Day (EoT)
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| No statistical analyses for this end point | |||||||||||||||||||||||||||
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End point title |
Safety | ||||||
End point description |
Clinical safety was addressed by recording AEs, physical examinations, weight, vital signs, electrocardiogram [ECG], laboratory assessments (hematology, biochemistry and urinalysis), ECOG, and concomitant medications/procedures.
The values listed below refer to the number of AEs.
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End point type |
Secondary
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End point timeframe |
From subject ICF signature until End of Treatment Visit.
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| No statistical analyses for this end point | |||||||
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Adverse events information
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Timeframe for reporting adverse events |
Continuously from signing of ICF until the last trial related activity.
Please refer to the CSR for more details about type of AEs.
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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 |
22.0
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Reporting groups
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Reporting group title |
Subjects affected by adverse events
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Reporting group description |
Overall, 169 subjects were screened and signed the ICF to participate in the trial (defined in this trial as the ENR population). Of these, 142 subjects were confirmed eligible on Cycle 1 Day 1, were enrolled in the trial and received at least one dose of trial medication (SAF population). The remainder of 27 subjects did not meet all eligibility criteria and were considered screen failures. ITT population was identical to SAF population. The Per Protocol population consisted of 31 subjects of the ITT population who completed the study. The study was terminated early because of efficacy risks and the PK parameters planned to be assessed in samples taken from the PK subset were not evaluated because no PK analysis was performed on the respective samples. Screened population (and who signed the ICF): 169 Safety set (SAF) population: 142 Intent-to-treat set (ITT) population: 142 Per Protocol set (PP) population: 31 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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06 Jun 2019 |
Protocol amendment V2.0, dated 06-Jun-2019:
The main changes were:
- The addition of exclusion criterion #10: Hypersensitivity to GnRH and its analogues,
- The addition to the safety section 1.6,
- The addition of explanation for study purpose in section 2.1
- The addition of explanation of expected adverse events in section 6.4.6 |
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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. | |||
| Due to the early termination of the study only 31 patients could finish the study according to the protocol whereas the numbre of patients with intention to treat was 142. | |||
