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

February 26, 2024 updated by: Debiopharm International SA

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

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).

Study Overview

Status

Active, not recruiting

Conditions

Study Type

Interventional

Enrollment (Estimated)

30

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

      • Copenaghen, Denmark, 2200
        • Rigshospitalet, Endokrinologisk afdeling
      • Angers, France, 49933
        • CHU Angers
      • Le Kremlin-bicetre, France, 94270
        • AP-HP Hôpital Bicêtre
      • Marseille, France, 13385
        • AP-HM - Hôpital de la Conception, Service d'Endocrinologie et Centre de Référence des Maladies Rares de l'hypophyse
      • Munich, Germany, 81667
        • Medicover Praxis fur Neuroendokrinologie
      • Petach Tikva, Israel, 49100
        • Rabin Medical Center, Beilinson Hospital, Clalit Health Services by Rabin Medical Center, Beilinson Hospita
      • Ramat Gan, Israel, 5265601
        • Sheba Medical Center, Endocrine institute
      • Milano, Italy, 20122
        • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano
      • Katowice, Poland, 40-514
        • Uniwersyteckie Centrum Kliniczne im. Prof. K. Gibinskiego Slaskiego Uniwersytetu Medycznego w Katowicach
      • Warszawa, Poland, 03-242
        • Mazowiecki Szpital Brodnowski - Zespol Oddzialow Chorob Wewnetrznych, Endokrynologii i Diabetologii
      • Barcelona, Spain, 08041
        • Hospital de la Santa Creu i Sant Pau Barcelon
      • Sevilla, Spain, 41013
        • Hospital Universitario Virgen del Rocio
      • Coventry, United Kingdom, CV2 2DX
        • University Hospital Coventry, WISDEM Centre, UHCW NHS Trust

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.]

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / 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.
Intramuscular (IM) injection
Sandostatin LAR will be administered as IM injection as pre-study treatment dose prior to Debio 4126 administration
Other Names:
  • Octreotide acetate
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.
Intramuscular (IM) injection
Sandostatin LAR will be administered as IM injection as pre-study treatment dose prior to Debio 4126 administration
Other Names:
  • Octreotide acetate
Somatulin ATG will be administered as deep subcutaneous (SC) injection as pre-study treatment dose prior to Debio 4126 administration
Other Names:
  • Lanreotide acetate

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Plasma Concentration of Debio 4126 in Acromegaly and GEP-NET Participants
Time Frame: 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.
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
Time Frame: Predose at Days -28 to -7; Postdose at multiple timepoints from Day 1 to Day 337
Predose at Days -28 to -7; Postdose at multiple timepoints from Day 1 to Day 337
Insulin-Like Growth Factor 1 (IGF-1) and Growth Hormone (GH) Levels in Acromegaly Participants
Time Frame: 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).
Baseline up to Week 48
Number of Participants With Carcinoid Syndrome Symptoms and use of Rescue Medication for Symptom Control in GEP-NET Participants
Time Frame: Baseline up to Week 48
Baseline up to Week 48
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
Time Frame: Up to Week 65
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
Time Frame: Up to Week 65
Pain VAS scale score will be assessed on 4-point rating scale, where 0=absent and 3=severe.
Up to Week 65

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 18, 2022

Primary Completion (Estimated)

November 1, 2024

Study Completion (Estimated)

December 1, 2024

Study Registration Dates

First Submitted

May 4, 2022

First Submitted That Met QC Criteria

May 4, 2022

First Posted (Actual)

May 6, 2022

Study Record Updates

Last Update Posted (Actual)

February 28, 2024

Last Update Submitted That Met QC Criteria

February 26, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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