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

Acromegaly Clinical Trial

— OXTEND-01  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05364944
• Other study ID #: Debio 4126-102
• Secondary ID: 2021-005035-23
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: May 18, 2022
• Est. completion date: December 2024

Study information

• Verified date: April 2024
• Source: Debiopharm International SA
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 30
• Est. completion date: December 2024
• Est. primary completion date: November 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.]

Related Conditions & MeSH terms

• Acromegaly
• Neuroendocrine Tumors

Intervention

Drug:
• Debio 4126
Intramuscular (IM) injection
• Sandostatin LAR
Sandostatin LAR will be administered as IM injection as pre-study treatment dose prior to Debio 4126 administration
• Somatuline ATG
Somatulin ATG will be administered as deep subcutaneous (SC) injection as pre-study treatment dose prior to Debio 4126 administration

Locations

Country	Name	City	State
Denmark	Rigshospitalet, Endokrinologisk afdeling	Copenaghen
France	CHU Angers	Angers
France	AP-HP Hopital Bicetre	Le Kremlin-bicetre
France	AP-HM - Hôpital de la Conception, Service d'Endocrinologie et Centre de Référence des Maladies Rares de l'hypophyse	Marseille
Germany	Medicover Praxis fur Neuroendokrinologie	Munich
Israel	Rabin Medical Center, Beilinson Hospital, Clalit Health Services by Rabin Medical Center, Beilinson Hospita	Petach Tikva
Israel	Sheba Medical Center, Endocrine institute	Ramat Gan
Italy	Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano	Milano
Poland	Uniwersyteckie Centrum Kliniczne im. Prof. K. Gibinskiego Slaskiego Uniwersytetu Medycznego w Katowicach	Katowice
Poland	Mazowiecki Szpital Brodnowski - Zespol Oddzialow Chorob Wewnetrznych, Endokrynologii i Diabetologii	Warszawa
Spain	Hospital de la Santa Creu i Sant Pau Barcelon	Barcelona
Spain	Hospital Universitario Virgen del Rocio	Sevilla
United Kingdom	University Hospital Coventry, WISDEM Centre, UHCW NHS Trust	Coventry
United Kingdom	Royal Free London NHS Foundation Trust	London

Sponsors (1)

Lead Sponsor	Collaborator
Debiopharm International SA

Countries where clinical trial is conducted

Denmark,  France,  Germany,  Israel,  Italy,  Poland,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Number of Participants With Carcinoid Syndrome Symptoms and use of Rescue Medication for Symptom Control in GEP-NET Participants		Baseline up to Week 48