Carcinoid Syndrome
Conditions
Brief summary
The purpose of the protocol is to assess the efficacy and safety of BIM 23A760 on patient's overall satisfaction in terms of symptom relief (diarrhoea and/or flushes) in patients with carcinoid syndrome after 24 weeks of treatment.
Interventions
DRUGBIM 23A760
BIM 23A760 is a solution at a concentration of 5 mg/mL ready for subcutaneous injection. BIM 23A760 dose of 1, 2, 4, 6 and 8 mg can be given to the patient according to a dose escalation and titration process. Patients will receive 24 weekly injections of BIM 23A760 during the treatment period. Patients eligible to continue the extension phase will be administered BIM 23A760 for further 52 weekly injections.
Sponsors
Ipsen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* The patient has a carcinoid syndrome defined as ≥3 stools/day and/or ≥3 flushes/week. * The patient has elevated 5-Hydroxyindoleacetic acid (above upper limit normal). * The patient has a well-differentiated mid-gut carcinoid tumour or serotonin secreting tumour of unknown localisation with hepatic metastasis.
Exclusion criteria
* The patient has undergone surgery related to a neuroendocrine tumour (NET) within 4 weeks prior to study entry or has surgery planned during the study. * The patient has received short acting somatostatin analogues (SSAs) within 2 weeks before study entry or has received short acting SSAs for more than 3 months. * The patient has received a radiolabelled SSA at any time before study entry. * The patient has received long acting SSAs under certain circumstances. * The patient has previously received any specific anti tumour treatment such as chemotherapy, (chemo)embolisation, radiotherapy or interferon in the last 6 months. * The patient has signs or symptoms of cardiac insufficiency. * The patient has an ejection fraction \<40% and/or clinically severe cardiac valvular regurgitation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients With a Positive Overall Satisfactory Relief of Symptoms (Diarrhoea and/or Flushes) on the Likert Scale | Week 24 | Patient satisfaction based on a Likert scale from 0-5 (0 being not satisfied and 5 being completely satisfied) |
Secondary
| Measure | Time frame |
|---|---|
| Minimum Concentration (Cmin) BIM 23A760 Plasma Levels | At 9 timepoints up to 1 week after 24th administration in week 24 |
| Concentration at 2 Hours Postdose (C2 Hours) BIM 23A760 Plasma Levels | At 8 timepoints up to week 24 |
| Number of Subjects Reported Adverse Events, Including Any Findings From an Examination of the Injection Site(s) | Up to week 26 |
| Change in the Quality of Life (QoL) Assessment | Week 24 |
| Change in 5 Hydroxyindoleacetic Acid (5 HIAA) and Chromogranin A | Week 24 |
| Percentage of Patients With Improvement in Symptoms (Diarrhoea and/or Flushes) | Up to week 24 |
Countries
Austria, Belgium, Czechia, Finland, France, Germany, Ireland, Israel, Italy, Latvia, Netherlands, Poland, Russia, Slovakia, Spain, Sweden, Ukraine, United Kingdom
Participant flow
Recruitment details
This study was terminated prematurely. Only 8 patients were treated in part A and no patients participated in part B.
Pre-assignment details
Patients screened were 15 and not treated were 7 (2 subjects were not included due to early termination of study by sponsor and 5 subjects failed to meet inclusion criteria).
Participants by arm
| Arm | Count |
|---|---|
| BIM 23A760 This dose adaptive study was planned to treat up to 20 patients in each starting dose cohort, with a maximum of three starting dose cohorts. The doses planned to be assessed were 1, 2, 4, 6 and 8 mg; however, the maximum starting dose was 4 mg. The starting dose of the first cohort was 1 mg and the first cohort would include at least five patients. After the first 15 patients were treated for 4 weeks, the results were to be reviewed by a Data Review Committee. An extension phase (Part B) was planned for those subjects completing the initial study and fulfilling specific eligibility criteria (symptoms control, willingness to participate, safety and tolerability).
BIM 23A760 was a solution at a concentration of 5 mg/mL ready for subcutaneous injection. BIM 23A760 doses of 1, 2, 4, 6 and 8 mg were to be given to the patient according to a dose escalation and titration process. Patients would have received 24 weekly injections of BIM 23A760 during the treatment period. | 8 |
| Total | 8 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Study termination by sponsor | 5 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | BIM 23A760 |
|---|---|
| Age, Continuous | 62.1 years STANDARD_DEVIATION 6.88 |
| Age, Customized Between 18 and 75 years | 8 participants |
| Diabetic status Diabetic | 0 participants |
| Diabetic status Nondiabetic | 8 participants |
| Post-menopausal status N/A - Not applicable | 2 participants |
| Post-menopausal status No | 0 participants |
| Post-menopausal status Yes | 6 participants |
| Race/Ethnicity, Customized Caucasian/ White | 8 participants |
| Region of Enrollment Belgium | 1 participants |
| Region of Enrollment Finland | 1 participants |
| Region of Enrollment Germany | 1 participants |
| Region of Enrollment Ireland | 1 participants |
| Region of Enrollment Netherlands | 1 participants |
| Region of Enrollment Russian Federation | 1 participants |
| Region of Enrollment United Kingdom | 2 participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 6 / 8 |
| serious Total, serious adverse events | 1 / 8 |
Outcome results
Primary
Percentage of Patients With a Positive Overall Satisfactory Relief of Symptoms (Diarrhoea and/or Flushes) on the Likert Scale
Patient satisfaction based on a Likert scale from 0-5 (0 being not satisfied and 5 being completely satisfied)
Time frame: Week 24
Population: Study was prematurely terminated and no data was collected/analyzed for this outcome measure.
Secondary
Change in 5 Hydroxyindoleacetic Acid (5 HIAA) and Chromogranin A
Time frame: Week 24
Population: Study was prematurely terminated and no data was collected/analyzed for this outcome measure.
Secondary
Change in the Quality of Life (QoL) Assessment
Time frame: Week 24
Population: Study was prematurely terminated and no data was collected/analyzed for this outcome measure.
Secondary
Concentration at 2 Hours Postdose (C2 Hours) BIM 23A760 Plasma Levels
Time frame: At 8 timepoints up to week 24
Population: Study was prematurely terminated and no data was collected/analyzed for this outcome measure.
Secondary
Minimum Concentration (Cmin) BIM 23A760 Plasma Levels
Time frame: At 9 timepoints up to 1 week after 24th administration in week 24
Population: Study was prematurely terminated and no data was collected/analyzed for this outcome measure.
Secondary
Number of Subjects Reported Adverse Events, Including Any Findings From an Examination of the Injection Site(s)
Time frame: Up to week 26
Population: Both ITT (Intent-To-Treat) and safety populations were the same analysis group. Treatment emergent adverse events (TEAE) reported by 2 or more patients (safety population) by primary system organ class.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BIM 23A760 | Number of Subjects Reported Adverse Events, Including Any Findings From an Examination of the Injection Site(s) | General Disorders & Administration Site Condition | 5 Participants |
| BIM 23A760 | Number of Subjects Reported Adverse Events, Including Any Findings From an Examination of the Injection Site(s) | Gastrointestinal Disorder | 4 Participants |
| BIM 23A760 | Number of Subjects Reported Adverse Events, Including Any Findings From an Examination of the Injection Site(s) | Nervous System Disorders | 3 Participants |
| BIM 23A760 | Number of Subjects Reported Adverse Events, Including Any Findings From an Examination of the Injection Site(s) | Infections and Infestations | 2 Participants |
| BIM 23A760 | Number of Subjects Reported Adverse Events, Including Any Findings From an Examination of the Injection Site(s) | Metabolism and Nutritional Disorders | 2 Participants |
| BIM 23A760 | Number of Subjects Reported Adverse Events, Including Any Findings From an Examination of the Injection Site(s) | Neoplasms Benign, Malignant and unspecified | 2 Participants |
| BIM 23A760 | Number of Subjects Reported Adverse Events, Including Any Findings From an Examination of the Injection Site(s) | Reproductive System and Breast Disorders | 2 Participants |
Secondary
Percentage of Patients With Improvement in Symptoms (Diarrhoea and/or Flushes)
Time frame: Up to week 24
Population: Study was prematurely terminated and no data was collected/analyzed for this outcome measure.