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

NCT05364944 | Terminated Phase 1

• 2 other identifiers: Debio 4126-1022021-005035-23
• Study Type: interventional
• Target: 19
• Locations: 8 countries
• Sites: 14

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).

Conditions

Acromegaly; GEP-NET

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• 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

  Up to Week 65

• Insulin-Like Growth Factor 1 (IGF-1) and Growth Hormone (GH) Levels in Acromegaly Participants

  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

Study Arms (2)

Cohort A: Participants With Acromegaly

EXPERIMENTAL

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; Drug: Sandostatin LAR; Drug: Somatuline ATG

Cohort B: Participants With GEP-NET

EXPERIMENTAL

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; Drug: Sandostatin LAR; Drug: Somatuline ATG

Interventions

Debio 4126 DRUG

Intramuscular (IM) injection

Cohort A: Participants With Acromegaly; Cohort B: Participants With GEP-NET

Sandostatin LAR DRUG

Sandostatin LAR will be administered as IM injection as pre-study treatment dose prior to Debio 4126 administration

Also known as: Octreotide acetate

Cohort A: Participants With Acromegaly; Cohort B: Participants With GEP-NET

Somatuline ATG DRUG

Somatulin ATG will be administered as deep subcutaneous (SC) injection as pre-study treatment dose prior to Debio 4126 administration

Also known as: Lanreotide acetate

Cohort A: Participants With Acromegaly; Cohort B: Participants With GEP-NET

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Debiopharm International SA: lead

Study Sites (14)

Rigshospitalet, Endokrinologisk afdeling

Copenhagen, 2200, Denmark

Location

CHU Angers

Angers, 49933, France

Location

AP-HP Hopital Bicetre

Le Kremlin-Bicêtre, 94270, France

Location

AP-HM - Hôpital de la Conception, Service d'Endocrinologie et Centre de Référence des Maladies Rares de l'hypophyse

Marseille, 13385, France

Location

Medicover Praxis fur Neuroendokrinologie

Munich, 81667, Germany

Location

Rabin Medical Center, Beilinson Hospital, Clalit Health Services by Rabin Medical Center, Beilinson Hospita

Petah Tikva, 49100, Israel

Location

Sheba Medical Center, Endocrine institute

Ramat Gan, 5265601, Israel

Location

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano

Milan, 20122, Italy

Location

Uniwersyteckie Centrum Kliniczne im. Prof. K. Gibinskiego Slaskiego Uniwersytetu Medycznego w Katowicach

Katowice, 40-514, Poland

Location

Mazowiecki Szpital Brodnowski - Zespol Oddzialow Chorob Wewnetrznych, Endokrynologii i Diabetologii

Warsaw, 03-242, Poland

Location

Hospital de la Santa Creu i Sant Pau Barcelon

Barcelona, 08041, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

Location

University Hospital Coventry, WISDEM Centre, UHCW NHS Trust

Coventry, CV2 2DX, United Kingdom

Location

Royal Free London NHS Foundation Trust

London, NW3 2QG, United Kingdom

Location

MeSH Terms

Conditions

Acromegaly; Gastro-enteropancreatic neuroendocrine tumor

Interventions

Octreotide; lanreotide

Condition Hierarchy (Ancestors)

Bone Diseases, Endocrine; Bone Diseases; Musculoskeletal Diseases; Hyperpituitarism; Pituitary Diseases; Hypothalamic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 4, 2022
• First Posted: May 6, 2022
• Study Start: May 18, 2022
• Primary Completion: October 29, 2024
• Study Completion: December 3, 2024
• Last Updated: November 17, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

ES (2); FR (3); IT (1); PL (2); GB (2); DK (1); IL (2); DE (1)