A Study to Assess the Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of Debio 4126 in Participants With Acromegaly or Functioning Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs)

Study Overview
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Brief Summary
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This is an open-label, single treatment arm, multicenter study to assess the pharmacokinetics (PK), pharmacodynamics (PD), safety, and tolerability of Debio 4126 in the treatment of participants with Acromegaly or Functioning Gastroenteropancreatic Neuroendocrine tumors (GEP-NETs).

Official Title
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A Phase 1b Study in Patients With Acromegaly or Functioning Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs) to Characterize the Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of Debio 4126, a 12-week Prolonged-release Octreotide Formulation

Conditions
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Acromegaly, GEP-NET

Intervention / Treatment
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* Drug: Debio 4126
* Drug: Sandostatin LAR
* Drug: Somatuline ATG


Participation Criteria
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Eligibility Criteria
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Main Inclusion Criteria: For Participants with Acromegaly: Treatment with octreotide LAR (≤30 mg dose once in 4 weeks [Q4W] IM) or lanreotide ATG (≤120 mg Q4W or 120 mg once in 6 weeks [Q6W] to once in 8 weeks [Q8W] as deep SC injection) for at least 6 months overall, and for at least 2 months at a stable dose as monotherapy for acromegaly treatment prior to entering Run-in (Day -28). Octreotide doses of 10, 20, and 30 mg are considered similar to lanreotide doses of 60, 90, and 120 mg. Thus, a switch between similar doses of the two products will be considered as the patient remaining on a stable dose, unless due to efficacy or safety Diagnosis of acromegaly by historical evidence of (persistent or recurrent) acromegaly will be carried out IGF-1 ≤1.3 x upper limit of normal (ULN) assessed centrally at screening For Participants with GEP-NETs: Treatment with octreotide LAR (≤ 30 mg dose Q4W IM) or lanreotide ATG (≤ 120 mg Q4W or 120 mg Q6W to Q8W as deep SC injection) for at least 6 months overall, and for at least 2 months at a stable dose as monotherapy for study disease treatment prior to entering Run-in (Day -28). Octreotide doses of 10, 20, and 30 mg are considered similar to lanreotide doses of 60, 90, and 120 mg. Thus, a switch between similar doses of the two products will be considered as the participant remaining on a stable dose, unless due to efficacy or safety Participants with functioning, well-differentiated (Grade 1 or Grade 2) GEP-NET with symptoms of carcinoid syndrome which are controlled by Sandostatin LAR, Somatuline ATG, or equivalent medications; sporadic use of rescue medication for symptom control, e.g., bowel movements and/or flushing, is allowed Main Exclusion Criteria: For Participants with Acromegaly and GEP-NETs: Known ongoing gallbladder or bile duct disease or acute or chronic pancreatitis Hypothyroidism not adequately treated with thyroid hormone replacement therapy Diabetic participants whose blood glucose is poorly controlled despite adequate therapy, as evidenced by glycated hemoglobin (HbA1c) >8.0% at screening Cardiology: Known left ventricular ejection fraction <50%, left ventricular hypertrophy, ventricular arrhythmias, bradycardia (heart rate <50 beats per minute [bpm]), cardiomyopathy New York Heart Association Class ≥3 heart failure Congenital long QT syndrome or Known family history of long QT syndrome or sudden cardiac death before the age of 50 Symptomatic Pulmonary embolism QT interval corrected for heart rate according to Fridericia's formula (QTcF) at screening >450 milliseconds (msec) for males and >470 msec for females, based on the average of a triplicate ECG For Participants with Acromegaly: Participants who received pituitary irradiation <2 years prior to enrollment as stereotactic radiotherapy or <3 years prior to enrollment for conventional radiotherapy Participants who received medical treatment with pasireotide (within 6 months prior to screening), pegvisomant (within 3 months prior to screening), dopamine agonists (within 3 months prior to screening) Participants who have undergone pituitary surgery within 6 months prior to screening For Participants with GEP-NETs: Participants with short-bowel syndrome Participants with poorly differentiated neuroendocrine carcinoma and/or high-grade neuroendocrine carcinoma Participants who have received any previous therapy with interferons, targeted therapies (e.g., everolimus, sunitinib, bevacizumab), chemotherapy or other anti-neoplastic systemic therapies administered for more than 1 month and within 12 weeks prior to the start of the Run-in period Participants having history of hepatic embolization, hepatic arterial chemoembolization, and/or selective internal radiation (SIR) therapy within less than 6 months prior to screening Participants who have received Peptide receptor radionuclide therapy (PRRT) therapy during the last 12 months prior to screening [Note: Other inclusion/exclusion criteria mentioned in the protocol may apply.]

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A: Participants With Acromegaly<br>Participants will receive Sandostatin Long-acting repeatable (LAR) or Somatuline Autogel (ATG) (or equivalent formulations of octreotide/lanreotide) in Run-in Period and further will receive Debio 4126 in this group. | Drug: Debio 4126<br>* Intramuscular (IM) injection<br>Drug: Sandostatin LAR<br>* Sandostatin LAR will be administered as IM injection as pre-study treatment dose prior to Debio 4126 administration<br>* Other names: Octreotide acetate;Drug: Somatuline ATG<br>* Somatulin ATG will be administered as deep subcutaneous (SC) injection as pre-study treatment dose prior to Debio 4126 administration<br>* Other names: Lanreotide acetate;|
| Experimental: Cohort B: Participants With GEP-NET<br>Participants will receive Sandostatin LAR or Somatuline ATG (or equivalent formulations of octreotide/lanreotide) in Run-in Period and further will receive Debio 4126 in this group. | Drug: Debio 4126<br>* Intramuscular (IM) injection<br>Drug: Sandostatin LAR<br>* Sandostatin LAR will be administered as IM injection as pre-study treatment dose prior to Debio 4126 administration<br>* Other names: Octreotide acetate;Drug: Somatuline ATG<br>* Somatulin ATG will be administered as deep subcutaneous (SC) injection as pre-study treatment dose prior to Debio 4126 administration<br>* Other names: Lanreotide acetate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma Concentration of Debio 4126 in Acromegaly and GEP-NET Participants | The PK of Debio 4126 will be evaluated in plasma. | Predose at Days -28 to -7; Postdose at multiple timepoints from Day 1 to Day 337 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of Ratio of Accumulation (Rac) of Octreotide in Plasma After Repeated Administration of Debio 4126 in Acromegaly and GEP-NET Participants |  | Predose at Days -28 to -7; Postdose at multiple timepoints from Day 1 to Day 337 | 
| Safety and Tolerability of Debio 4126 as Assessed by Number of Participants With At Least one Treatment Emergent Adverse Events (TEAE) in Acromegaly and GEP-NET Participants |  | Up to Week 65 | 
| Local Tolerability of Debio 4126 as Assessed by Pain at Injection Site Based on Pain Visual Analog Scale (VAS) Score in Acromegaly and GEP-NET Participants | Pain VAS scale score will be assessed on 4-point rating scale, where 0=absent and 3=severe. | Up to Week 65 | 
| Insulin-Like Growth Factor 1 (IGF-1) and Growth Hormone (GH) Levels in Acromegaly Participants | The blood samples will be collected to assess changes in the levels of IGF-1 (in µg/L) and GH (in µg/L). | Baseline up to Week 48 | 
| Number of Participants With Carcinoid Syndrome Symptoms and use of Rescue Medication for Symptom Control in GEP-NET Participants |  | Baseline up to Week 48 |