A Dose Finding Study of Debio 4228 in Participants With Advanced Prostate Cancer

A Phase 2, Randomized, Open-Label, Dose-Finding Study of Debio 4228, an Extended-Release Formulation of Gonadotropin-Releasing Hormone Antagonist in Participants With Advanced Prostate Cancer

The primary purpose of this study is to determine the pharmacokinetics (PK) and pharmacodynamics (PD) of Debio 4228.

Study Overview

• Status: Completed
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: Debio 4228

• Study Type: Interventional
• Enrollment (Actual): 55
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Clermont-Ferrand, France, 63011
    • Centre Jean Perrin
  • Dijon, France, 21000
    • Centre Georges François Leclerc
  • Nantes, France, 44093
    • CHU de Nantes - Hôtel Dieu
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall d'Hebron
  • Barcelona, Spain, 8036
    • Hospital Clinic Barcelona
  • Madroñera, Spain, 28040
    • Hospital Clinico San Carlos
  • Valencia, Spain, 46009
    • Instituto Valenciano de Oncología
• United States
  • Arizona
    • Mesa, Arizona, United States, 85206
      • Urologic Surgeons of Arizona
    • Queen Creek, Arizona, United States, 85140
      • East Valley Urology Center of Arizona
  • California
    • Bakersfield, California, United States, 93301
      • Bakersfield Institute of Advanced Urology
    • Chula Vista, California, United States, 91910
      • Grimaldi Urology
    • Fresno, California, United States, 93722
      • Valley Urology
    • Los Angeles, California, United States, 90048
      • Tower Urology,
    • Montebello, California, United States, 90640
      • Alarcon Urology Center
    • Murrieta, California, United States, 92563
      • Urology Center of Southern California
  • Florida
    • Miami, Florida, United States, 33165
      • Biogenix Molecular
  • New York
    • New York, New York, United States, 10029
      • Icahn School Of Medicine At Mount Sinai
  • Oregon
    • Springfield, Oregon, United States, 97477
      • Oregon Urology Institut
  • South Carolina
    • Myrtle Beach, South Carolina, United States, 29572
      • Carolina Urologic Research Center
  • Virginia
    • Virginia Beach, Virginia, United States, 23462
      • Urology of Virginia
  • Washington
    • Spokane, Washington, United States, 99208
      • Summit Cancer Centers of North Spokane

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Participant with histologically confirmed diagnosis of prostate cancer, with one of the following:

   1. Newly diagnosed androgen-sensitive locally advanced or metastatic disease; or
   2. Localized disease not suitable for local primary intervention with curative intent.
2. Participant judged by the Study Investigator to be candidate for continuous androgen deprivation therapy (ADT).
3. Baseline morning serum testosterone levels >150 ng/dL at screening visit.
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
5. Life expectancy of at least 6 months.
6. Adequate bone marrow, hepatic, and renal function at the screening visit.

[Note: Other protocol and subprotocol-defined criteria apply]

Exclusion Criteria:

1. Previous ADT (neoadjuvant or adjuvant hormonal therapy) for ≥6 months duration and <6 months treatment-free interval before start of screening.
2. Participant requires combination with androgen deprivation therapy with the exception of enzalutamide.
3. History of bilateral orchiectomy, adrenalectomy, or hypophysectomy.
4. Received chemotherapy or cryotherapy within 8 weeks prior to the start of screening for the treatment of prostate cancer.
5. Abnormal cardiovascular function or diabetes.
6. Use of exogenous testosterone within 6 months before the start of screening.
7. Major surgery within 4 weeks before the start of screening.
8. Cancer disease within the last two years except for prostate cancer and some skin cancers.

[Note: Other protocol and subprotocol-defined criteria apply]

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 2: Debio 4228 Dose Level 2; Participants will receive a single IM administration of dose level 2 Debio 4228 on Day 1.	Drug: Debio 4228; Administered as IM injection.
Experimental: Cohort 3; If any alternative dose is deemed necessary based on preliminary data, participants may be enrolled in Cohort 3 to receive Debio 4228 loading dose IM, on Day 1 followed by a maintenance dose IM, 12 weeks after receiving the loading dose (Day 85).	Drug: Debio 4228; Administered as IM injection.
Experimental: Cohort 1: Debio 4228 Dose Level 1; Participants will receive a single intramuscular (IM) administration of dose level 1 Debio 4228 on Day 1. Enrolment for cohort 1 was discontinued as per protocol amendment v5.0	Drug: Debio 4228; Administered as IM injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Plasma Concentration of Debio 4228 at Week 12 (C84d)	Cohorts 1 and 2: Post-dose on Day 84; Cohort 3: Post-dose on Days 84 and 168
Serum Concentration of Testosterone	Cohorts 1 and 2: Predose and at multiple time points post-dose from Days 1 to 85; Cohort 3: Predose and at multiple time points post-dose from Days 1 to 169
Maximum Plasma Concentration (Cmax) of Debio 4228	Cohorts 1 and 2: Predose and at multiple time points post-dose up to Day 169; Cohort 3: Predose and at multiple time points post-dose up to Day 169
Area Under the Concentration-time Curve of Debio 4228 Over 12 weeks (AUC84d)	Cohorts 1 and 2: Predose and at multiple time points post-dose up to Day 84; Cohort 3: Predose and at multiple time points post-dose up to Day 169

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of Participants who Maintained a Testosterone Castration (Testosterone Level of <50 ng/dL and <20 ng/dL)	Cohort 3: Days 29 to 169
Time to Achieve Testosterone Castration (Testosterone Level of <50 ng/dL and <20 ng/dL)	Cohorts 1 and 2: Day 1 up to Day 85; Cohort 3: Day 1 up to Day 169
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) By Severity	Cohorts 1 and 2: Up to Day 169; Cohort 3: Up to Day 197
Number of Participants With Related TEAEs, Serious TEAEs, Adverse Events of Special Interest (AESIs), TEAEs Leading to Treatment Delay, and/or Discontinuation, and Death	Cohorts 1 and 2: Up to Day 169; Cohort 3: Up to Day 197
Number of Participants With Clinically Significant Abnormalities in Laboratory, Vital Signs, and Electrocardiogram (ECG) Parameters	Cohorts 1 and 2: Up to Day 169; Cohort 3: Up to Day 197
Percent Change From Baseline in Serum Prostate-Specific Antigen (PSA) Over Time	Cohorts 1 and 2: Baseline up to Day 85; Cohort 3: Baseline up to Day 169
Change From Baseline of Serum Luteinizing Hormone (LH) Over Time	Cohorts 1 and 2: Baseline up to Day 85; Cohort 3: Baseline up to Day 169
Change From Baseline in Serum Follicle-Stimulating Hormone (FSH) Over Time	Cohorts 1 and 2: Baseline up to Day 85; Cohort 3: Baseline up to Day 169
Number of Participants who Achieved and Maintained a Testosterone Castration (Testosterone Level of <50 [Nanograms per Deciliter] ng/dL and <20 ng/dL)	Cohorts 1, 2, and 3: Days 29 to 85
Number of Participants who Experience Local Reactions Categorized as Erythema, Swelling, and Induration at the Injection Site	Cohorts 1 and 2: Immediately, at 2 and 24 hours post-injection on Day 1; Cohort 3: Immediately, at 2 and 24 hours post-injection on Days 1 and 85
Number of Participants who Experience Pain at Injection Site	Cohorts 1 and 2: Immediately, at 2 and 24 hours post-injection on Day 1; Cohort 3: Immediately, at 2 and 24 hours post-injection on Days 1 and 85

Collaborators and Investigators

• Sponsor: Debiopharm International SA

Study record dates

Study Major Dates

• Study Start (Actual): May 23, 2024
• Primary Completion (Actual): June 24, 2026
• Study Completion (Actual): July 22, 2026

Study Registration Dates

• First Submitted: April 29, 2024
• First Submitted That Met QC Criteria: April 29, 2024
• First Posted (Actual): May 2, 2024

Study Record Updates

• Last Update Posted (Actual): August 24, 2026
• Last Update Submitted That Met QC Criteria: August 21, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms
• Other Study ID Numbers: Debio 4228-201; U1111-1298-8943 (Other Identifier: WHO Unique Trial Identifier); 2024-511038-11 (Other Identifier: EU CT Number)

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: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No