Clinical trial NCT05364944: A Study to Assess the Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of Debio 4126 in Participants With Acromegaly or Functioning Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs)
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Acromegaly
GEP-NET
Lead sponsor: Debiopharm International SA
Sponsor class: INDUSTRY
First posted: 2022-05-06
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: 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:

  1. Known left ventricular ejection fraction \<50%, left ventricular hypertrophy, ventricular arrhythmias, bradycardia (heart rate \<50 beats per minute \[bpm\]), cardiomyopathy
  2. New York Heart Association Class ≥3 heart failure
  3. Congenital long QT syndrome or
  4. Known family history of long QT syndrome or sudden cardiac death before the age of 50
  5. Symptomatic Pulmonary embolism
  6. 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

\[Note: Other inclusion/exclusion criteria mentioned in the protocol may apply.\]

Primary outcomes:
measure: Plasma Concentration of Debio 4126 in Acromegaly and GEP-NET Participants
timeFrame: Predose at Days -28 to -7; Postdose at multiple timepoints from Day 1 to Day 337
Secondary outcomes:
measure: Assessment of Ratio of Accumulation (Rac) of Octreotide in Plasma After Repeated Administration of Debio 4126 in Acromegaly and GEP-NET Participants
timeFrame: Predose at Days -28 to -7; Postdose at multiple timepoints from Day 1 to Day 337
measure: 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
timeFrame: Up to Week 65
measure: 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
timeFrame: Up to Week 65
measure: Insulin-Like Growth Factor 1 (IGF-1) and Growth Hormone (GH) Levels in Acromegaly Participants
timeFrame: Baseline up to Week 48
measure: Number of Participants With Carcinoid Syndrome Symptoms and use of Rescue Medication for Symptom Control in GEP-NET Participants
timeFrame: Baseline up to Week 48
Other outcomes:
Locations:
city: Copenaghen
country: Denmark
facility: Rigshospitalet, Endokrinologisk afdeling
city: Angers
country: France
facility: CHU Angers
city: Le Kremlin-bicetre
country: France
facility: AP-HP Hopital Bicetre
city: Marseille
country: France
facility: AP-HM - Hôpital de la Conception, Service d'Endocrinologie et Centre de Référence des Maladies Rares de l'hypophyse
city: Munich
country: Germany
facility: Medicover Praxis fur Neuroendokrinologie
city: Petach Tikva
country: Israel
facility: Rabin Medical Center, Beilinson Hospital, Clalit Health Services by Rabin Medical Center, Beilinson Hospita
city: Ramat Gan
country: Israel
facility: Sheba Medical Center, Endocrine institute
city: Milano
country: Italy
facility: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano
city: Katowice
country: Poland
facility: Uniwersyteckie Centrum Kliniczne im. Prof. K. Gibinskiego Slaskiego Uniwersytetu Medycznego w Katowicach
city: Warszawa
country: Poland
facility: Mazowiecki Szpital Brodnowski - Zespol Oddzialow Chorob Wewnetrznych, Endokrynologii i Diabetologii
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau Barcelon
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Coventry
country: United Kingdom
facility: University Hospital Coventry, WISDEM Centre, UHCW NHS Trust
city: London
country: United Kingdom
facility: Royal Free London NHS Foundation Trust
Study officials:
References: