OXTEND-01: A Study to Assess the Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of Debio 4126 in Participants With Acromegaly or Functioning Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs)

• Sponsor: Debiopharm International SA (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT05364944
• Collaborator: (none)
• Enrollment: 30
• Locations: 35
• Arms: 2
• Anticipated Duration (Months): 32.5
• Patients Per Site: 0.9
• Patients Per Site Per Month: 0

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Acromegaly; GEP-NET	Drug: Debio 4126; Drug: Sandostatin LAR; Drug: Somatuline ATG	Phase 1

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 30 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: May 18, 2022
• Anticipated Primary Completion Date: Jan 1, 2025
• Anticipated Study Completion Date: Feb 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort A: Participants With Acromegaly 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; Intramuscular (IM) injection; Drug: Sandostatin LAR; Sandostatin LAR will be administered as IM injection as pre-study treatment dose prior to Debio 4126 administration; Other Names: Octreotide acetate ; Drug: Somatuline ATG; Somatulin ATG will be administered as deep subcutaneous (SC) injection as pre-study treatment dose prior to Debio 4126 administration; Other Names: Lanreotide acetate
Experimental: Cohort B: Participants With GEP-NET 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; Intramuscular (IM) injection; Drug: Sandostatin LAR; Sandostatin LAR will be administered as IM injection as pre-study treatment dose prior to Debio 4126 administration; Other Names: Octreotide acetate ; Drug: Somatuline ATG; Somatulin ATG will be administered as deep subcutaneous (SC) injection as pre-study treatment dose prior to Debio 4126 administration; Other Names: Lanreotide acetate

Outcome Measures

Primary Outcome Measures

1. Plasma Concentration 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]

   The PK of Debio 4126 will be evaluated in plasma.

Secondary Outcome Measures

1. 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]

2. 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 61]

3. 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 61]

   Pain VAS scale score will be assessed on 4-point rating scale, where 0=absent and 3=severe.

4. Insulin-Like Growth Factor 1 (IGF-1) and Growth Hormone (GH) Levels in Acromegaly Participants [Baseline up to Week 48]

   The blood samples will be collected to assess changes in the levels of IGF-1 (in µg/L) and GH (in µg/L).

5. Number of Participants With Carcinoid Syndrome Symptoms and use of Rescue Medication for Symptom Control in GEP-NET Participants [Baseline up to Week 48]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Main Inclusion Criteria:

For Participants with Acromegaly:

• Treatment with a stable dose of octreotide LAR (≤30 mg dose once in 4 weeks [Q4W] IM) or lanreotide ATG (≤120 mg Q4W as deep SC injection) for at least 2 months as monotherapy for acromegaly treatment prior to entering Run-in (Day -28)

• 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 a stable dose of octreotide LAR (≤ 30 mg dose Q4W IM) or lanreotide ATG (≤ 120 mg Q4W as deep SC injection) for at least 2 months prior to entering Run-in (Day -28)

• 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. Left ventricular ejection fraction, left ventricular hypertrophy, ventricular arrhythmias, bradycardia, cardiomyopathy

2. Heart failure

3. Congenital long QT syndrome or

4. Known family history of long QT syndrome or sudden cardiac death

5. 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

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), or other investigational agents (within 30 days or 5 half-lives prior to screening, whichever is longer)

• 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.]

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Rigshospitalet, Endokrinologisk afdeling	Copenaghen		Denmark	2200
2	CHU Angers	Angers		France	49933
3	AP-HP Hopital Bicetre	Le Kremlin-bicetre		France	94270
4	AP-HM - Hôpital de la Conception, Service d'Endocrinologie et Centre de Référence des Maladies Rares de l'hypophyse	Marseille		France	13385
5	CHU Bordeaux - Hôpital Haut-Lévêque	Pessac		France	33604
6	Universitaetsklinikum Bonn, Medizinische Klinik und Poliklinik I,	Bonn		Germany	53127
7	Medicover Praxis fur Neuroendokrinologie	Munich		Germany	81667
8	Universitätsklinikum München - Medizinische Klinik und Poliklinik IV, Medizinische Klinik und Poliklinik IV Department of Nephrology	München		Germany	80802
9	Semmelweis Egyetem - II. Belgyogyaszati Klinika (Internal Medicine), Klinikai Farmakológiai Részleg	Budapest		Hungary	H-1083
10	Debreceni Egyetem Klinikai Kozpont, Klinikai Farmakológiai részleg	Debrecen		Hungary	H-4032
11	Hadassah Ein-Karem Medical Center	Jerusalem		Israel	9112001
12	Rabin Medical Center, Beilinson Hospital, Clalit Health Services by Rabin Medical Center, Beilinson Hospita	Petach Tikva		Israel	49100
13	Sheba Medical Center, Endocrine institute	Ramat Gan		Israel	5265601
14	Tel Aviv Sourasky Medical Center, Institute of Endocrinology, metabolism and hypertension	Tel Aviv		Israel	6423906
15	Istituto Romagnolo per lo Studio dei Tumori Dino Amadori	Meldola		Italy	47014
16	Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano	Milano		Italy	20122
17	Fondazione Policlinico Universitario A. Gemelli IRCCS - Universita Cattolica del Sacro Cuore	Rome		Italy	00168
18	Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy, Oddzial Gliwice, Zaklad Medycyny Nuklearnej i Endokrynologii Onkologicznej	Gliwice		Poland	41-101
19	Uniwersyteckie Centrum Kliniczne im. Prof. K. Gibinskiego Slaskiego Uniwersytetu Medycznego w Katowicach	Katowice		Poland	40-514
20	Szpital Uniwersytecki Krakow - Oddzial Kliniczny Endokrynologii,	Kraków		Poland	30-688
21	Mazowiecki Szpital Brodnowski - Zespol Oddzialow Chorob Wewnetrznych, Endokrynologii i Diabetologii	Warszawa		Poland	03-242
22	Instituto Português de Oncologia de Lisboa Francisco Gentil	Lisboa		Portugal	1099-023
23	Centro Hospitalar Universitário São João, EPE, Departamento de Endocrinologia, Diabetes e Metabolismo	Porto		Portugal	4200 - 319
24	Scientific and Research Medical complex Vashe Zdorovie, LLC, State Autonomous Healthcare Institution, Interregional Clinical Diagnostic Cente	Kazan		Russian Federation	42010
25	Novosibirsk State Regional Clinical Hospital	Novosibirsk		Russian Federation	630087
26	Siberian State Medical University	Tomsk		Russian Federation	634050
27	Hospital Universitario Vall d´Hebron	Barcelona		Spain	08035
28	Hospital de la Santa Creu i Sant Pau Barcelon	Barcelona		Spain	08041
29	Hospital Universitario 12 de Octubre	Madrid		Spain	28041
30	Hospital Universitario Virgen del Rocio	Sevilla		Spain	41013
31	Uppsala University Hospital	Uppsala		Sweden	SE-751 85
32	University Hospital Coventry, WISDEM Centre, UHCW NHS Trust	Coventry		United Kingdom	CV2 2DX
33	Royal Free London NHS Foundation Trust, Royal Free Hospital	London		United Kingdom	NW3 2QG
34	Cancer Research UK - Christie Hospital Foundation NHS Trust - Dept of Medical Oncology, Christie Hospital NHS Foundation Trust	Manchester		United Kingdom	M20 4BX
35	Cancer Research UK - Christie Hospital Foundation NHS Trust - Endocrinology Department, Endocrinology department, The Christie	Manchester		United Kingdom	M20 4BX

Sponsors and Collaborators

• Debiopharm International SA

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Debiopharm International SA
• ClinicalTrials.gov Identifier: NCT05364944
• Other Study ID Numbers: Debio 4126-102; 2021-005035-23
• First Posted: May 6, 2022
• Last Update Posted: Aug 22, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Neuroendocrine Tumors; Acromegaly; Octreotide; Lanreotide

Study Results

No Results Posted as of Aug 22, 2022