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)

Debiopharm

Status and phase: Terminated; Phase 1

Conditions: GEP-NET; Acromegaly

Treatments: Drug: Somatuline ATG; Drug: Sandostatin LAR; Drug: Debio 4126

Study type: Interventional

Funder types: Industry

Identifiers

NCT05364944

Debio 4126-102

2021-005035-23 (EudraCT Number)

Details and patient eligibility

About

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).

Enrollment: 19 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.]

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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19 participants in 2 patient groups

Cohort A: Participants With Acromegaly

Experimental group

Description:

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.

Treatment:

Drug: Debio 4126

Drug: Sandostatin LAR

Drug: Somatuline ATG

Cohort B: Participants With GEP-NET

Experimental group

Description:

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.

Treatment:

Drug: Debio 4126

Drug: Sandostatin LAR

Drug: Somatuline ATG