| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| acromegaly; neuroendocrine tumours |
|
| E.1.1.1 | Medical condition in easily understood language |
| acromegaly; neuroendocrine tumours |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Hormonal diseases [C19] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 17.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10000599 |
| E.1.2 | Term | Acromegaly |
| E.1.2 | System Organ Class | 10014698 - Endocrine disorders |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 17.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10052399 |
| E.1.2 | Term | Neuroendocrine tumour |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.3 | Condition being studied is a rare disease | Yes |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To characterise the PK profile of octreotide after each injection of CAM2029 as compared with baseline PK Sandostatin® LAR® in patients with acromegaly and NETs |
|
| E.2.2 | Secondary objectives of the trial |
The secondary objectives in patients with acromegaly are as follows:
•To assess the safety and tolerability of CAM2029
•To compare the effect of treatment and exposure with CAM2029 on the response rate of insulin-like growth factor 1 (IGF-1) at Day 84 with baseline treatment with Sandostatin LAR, ie, normalisation of IGF-1 adjusted for age and gender
•To compare the effect of treatment and exposure with CAM2029 on the reduction of mean growth hormone (GH) level to less than 2.5 µg/L at Day 84 with baseline treatment with Sandostatin LAR
•To characterise IGF-1 profiles after treatment with CAM2029 as compared with baseline treatment with Sandostatin LAR
•To compare the proportions of patients who have normalised GH and IGF-1 levels at Day 84 with baseline treatment with Sandostatin LAR
The secondary objectives in patients with NETs are as follows:
•To assess the safety and tolerability of CAM2029
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Inclusion criteria for patients with Acromegaly;
1.Patients from whom written informed consent to participate in the study has been obtained prior to any screening procedures.
2.Male or female patients ≥18 years of age.
3.Patients with acromegaly currently being treated with no medical treatment for acromegaly other than Sandostatin LAR (also Longastatina LAR for Italy).
4.Patients currently receiving Sandostatin LAR at a stable dose of 10 mg, 20 mg or 30 mg i.m. given every 28 days for at least 2 months before the start of the Last Sandostatin LAR Dose Assessment Phase (Day -28)
Inclusion criteria for patients with NETs;
1.Patients from whom written informed consent to participate in the study has been obtained prior to any screening procedures.
2.Male or female patients ≥18 years of age.
3.Patients with functional, well-differentiated (G1 or G2) neuroendocrine tumour (NET) with symptoms of carcinoid (bowel movements and/or flushing).
4.Patients currently receiving medical treatment with Sandostatin LAR (also Longastatina LAR for Italy) for symptom control at stable doses of 10 mg, 20 mg or 30 mg i.m. given every 28 days for at least 2 months before the start of the Last Sandostatin LAR Dose Assessment Phase (Day -28).
5.Patients with controlled symptoms, i.e., who do not require rescue medication with Sandostatin IR s.c. during Screening.
6.Patients not on treatment with any other agents for the treatment of NET (e.g., interferon, chemotherapy, radiotherapy, targeted agents).
|
|
| E.4 | Principal exclusion criteria |
Exclusion criteria for patients with Acromegaly:
1.Patients with inadequate bone marrow function as determined by WBC <3.0 × 109/L, and/or Platelets <100 × 109/L, and/ or Hgb <90% LLN.
2.Patients with abnormal coagulation (prothrombin time [PT] and/ or partial thromboplastin time [PTT] elevated by ≥30% above normal limits).
3.Patients with impaired liver function as determined by ALT and/ or AST more than 2 × upper limit of normal (ULN), total serum bilirubin >2.0 × ULN, or serum albumin <0.67 × lower limit of normal (LLN). Liver disease or history of liver disease
4.Patients with congestive heart failure, sustained ventricular tachycardia, ventricular fibrillation, clinically significant bradycardia or advanced heart block. Patients with a screening or baseline (Days -28 to -1) QTcF >450 msec for males, and QTcF >460 msec for females, and patients with sustained or clinically significant cardiac arrhythmias.
5.Patients with risk factors for Torsades de Pointes such as hypokalaemia, hypocalcaemia and hypomagnesemia, cardiac failure, clinically significant/ symptomatic bradycardia, and taking concomitant medication(s) known to prolong the QT interval.
6.Patients with impaired renal function as determined by serum creatinine >1.5 x ULN at screening.
7.Diabetic patients whose blood glucose is poorly controlled despite adequate therapy, as evidenced by glycosylated haemoglobin (HbA1C) >8.0% at screening.
8.Patients who require a surgical intervention for relief of any sign or symptom associated with tumour compression. Patients with compression of the optic chiasm causing acute clinically significant visual field defects.
9.Patients who have undergone major surgery/surgical therapy within 2 months before screening, or patients who are scheduled for any surgery within 6 months of starting this study.
10.Patients with active malignant disease within the last 5 years (with the exception of basal cell carcinoma or carcinoma in situ of the cervix).
Exclusion criteria for patients with NET:
1.Patients with poorly differentiated neuroendocrine carcinoma, high-grade neuroendocrine carcinoma, adenocarcinoid, pancreatic islet cell carcinoma, insulinoma, glucagonoma, gastrinoma, goblet cell carcinoid, typical and atypical lung carcinoids, large cell neuroendocrine carcinoma and small cell carcinoma.
2.Patients with carcinoid syndrome refractory to treatment with conventional doses of SSAs.
3.Patients with inadequate bone marrow function as determined by ANC <1.5 × 109/L, and /or WBC <3.0 × 109/L, and/or Platelets <100 × 109/L, and/ or Hgb <9 g/dL.
4.Patients with abnormal coagulation (prothrombin time [PT] and/ or partial thromboplastin time [PTT] elevated by ≥30% above normal limits).
5.Patients with impaired liver function as determined by ALT and/ or AST >2 × upper limit of normal (ULN) without liver metastases, or > 5 x ULN if documented liver metastases; total serum bilirubin >2.0 × ULN, or serum albumin <0.67 × lower limit of normal (LLN). Liver disease or history of liver disease such as cirrhosis, chronic active hepatitis B and C or chronic persistent hepatitis.
6.Patients with congestive heart failure, sustained ventricular tachycardia, ventricular fibrillation, clinically significant bradycardia or advanced heart block. Patients with a screening or baseline (Days -28 to -1) QTcF >450 msec for males, and QTcF >460 msec for females, and patients with sustained or clinically significant cardiac arrhythmias.
7.Patients with risk factors for Torsades de Pointes such as hypokalaemia, hypocalcaemia and hypomagnesemia, cardiac failure, clinically significant/ symptomatic bradycardia, and taking concomitant medication(s) known to prolong the QT interval.
8.Patients with impaired renal function as determined by serum creatinine >1.5 x ULN at screening.
9.Patients with short-bowel syndrome.
10.Diabetic patients whose blood glucose is poorly controlled despite adequate therapy, as evidenced by glycosylated haemoglobin (HbA1C) >8.0% at Screening.
11.Patients who have undergone major surgery/surgical therapy within 2 months before screening, or patients who are scheduled for any surgery within 6 months of starting this study. Patients who have not recovered from any adverse effects from surgery/radiotherapy.
12.History of hepatic embolisation, hepatic arterial chemoembolisation, and/or selective internal radiation therapy (e.g., SIR-Spheres) within less than 6 months prior to Screening. Scheduled hepatic embolisation, hepatic arterial chemoembolisation, and/or selective internal radiation therapy (e.g., SIR-Spheres) within 6 months of starting this study.
13.Patients with additional active malignant disease within the last 5 years (with the exception of basal cell carcinoma or carcinoma in situ of the cervix).
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| PK. The following variables are considered primary PK variables: AUC0-28d, Ctrough, and Cmax of octreotide. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Continuously throughout the study, see protocol |
|
| E.5.2 | Secondary end point(s) |
Safety endpoints (all patients):
•Incidence of treatment emergent AEs, including systemic tolerability and local tolerability (erythema, swelling, and pain)
•Changes in vital sign measurements (pulse rate, systolic and diastolic blood pressure, and body temperature), clinical laboratory investigations (haematology, coagulation tests, biochemistry, , endocrinology, and pregnancy test), and physical examination findings
•ECG results (ECGs to be analysed centrally
•ECG analysis based on QT and corrected QT according to Fridericia’s formula (QTcF) (treatment-emergent QTcF >450 msec, >480 msec, and >500 msec and change from baseline >30 msec and >60 msec)
•Results of the ultrasound examination of gallbladder
Efficacy endpoints for patients with acromegaly:
•Response rate of IGF-1 i.e. normalisation of IGF-1 (adjusted for age and gender) at baseline and at Day 84
•Proportion of patients with Reduction of mean GH level <2.5µg/L at baseline and at Day 84
•Change from baseline of IGF-1 and GH levels and maximum inhibition and AUC over 28 days of IGF-1 and GH levels
•Proportion of patients who have normalised GH and IGF-1 levels 1 (adjusted for age and gender) at baseline and at Day 84
Exploratory endpoint for patients with acromegaly:
•Octreotide concentration vs IGF-1 and GH modeling
Exploratory endpoints for patients with NETs:
•Symptoms of Carcinoid syndrome (bowel movements, flushing) with CAM2029 and Sandostatin LAR.
•Use of rescue medication |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Continuously throughout the study, see protocol |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 1 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 20 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 0 |
| E.8.9.1 | In the Member State concerned months | 7 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 0 |
| E.8.9.2 | In all countries concerned by the trial months | 7 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
Print
