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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Debiopharm International SA

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male

Therapeutic area

Diseases [C] - Male Urogenital Diseases [C12], Diseases [C] - Neoplasms [C04]

Trial duration

24 Sep 2024 → ongoing

Decision date (initial)

2024-07-17

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Debiopharm International S.A.

External identifiers

EU CT number

2024-511038-11-00

WHO UTN

U1111-1298-8943

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Efficacy, Pharmacodynamic

To determine the PK/PD of Debio 4228

Secondary objectives 7

1. To evaluate the efficacy of Debio 4228 in achieving and maintaining castration
2. To evaluate the efficacy of Debio 4228 in terms of time to castration
3. To assess the local tolerability at the injection site
4. To assess injection site pain
5. To assess the safety profile of Debio 4228
6. To assess the serum prostate-specific antigen (PSA) level over time
7. To assess the change of serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels over time

Conditions and MedDRA coding

advanced prostate cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Participant with histologically confirmed diagnosis of prostate cancer, with one of the following: a. Newly diagnosed androgen-sensitive locally advanced or metastatic disease; b. Localized disease not suitable for local primary intervention with curative intent.
2. Participant judged by the Study Investigator to be candidate for continuous ADT
3. Baseline morning serum testosterone levels >150 ng/dL at screening visit
4. Age ≥18 years
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
6. Life expectancy of at least 6 months
7. Adequate bone marrow, hepatic, and renal function at the screening visit
8. Other protocol and subprotocol defined criteria apply.

Exclusion criteria 9

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
9. Other protocol and subprotocol-defined criteria apply.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Degarelix plasma PK profile and PK parameters over 12 weeks after Debio 4228 dosing, including but not limited to: - Maximum concentration (Cmax) - Area under the concentration-time curve over 12 weeks (AUC84d) - Concentration at 12 weeks (C84d) This will be derived for each treatment period.
2. Testosterone serum concentration profile from Day 1 to Day 85 for all cohorts and from Day 85 to Day 169 in case of Cohort 3

Secondary endpoints 10

1. Achievement and maintenance of testosterone castration (testosterone level <50 ng/dL and <20 ng/dL) from Day 29 to Day 85 for all cohorts
2. Maintenance of testosterone castration (testosterone level <50 ng/dL and <20 ng/dL) from Day 29 to Day 169 for Cohort 3
3. Time to castration (testosterone level <50 ng/dL and <20 ng/dL)
4. Investigator’s assessment (4-point rating scale) of erythema, swelling, and induration at the injection site immediately after Debio 4228 injection, 2 hours, and 24 hours (Day 2) after Debio 4228 injection
5. Participants’ self-assessment of pain at the injection site immediately after Debio 4228 injection, 2 hours, and 24 hours (Day 2) after Debio 4228 injection using Numeric Pain Rating Scale (NPRS)
6. Incidence and severity of treatment-emergent adverse events (TEAEs), related TEAEs, serious TEAEs, adverse events of special interest (AESIs), death, and TEAEs leading to treatment delay, and/or discontinuation, graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0;
7. Percentage of change of PSA over time (per scheduled timepoint)
8. Time course of changes of LH and FSH (per scheduled timepoint)
9. Safety laboratory parameters and related severity based on NCI-CTCAE version 5.0
10. Changes from baseline in vital signs, weight, and electrocardiogram (ECG)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Debiopharm International SA

Sponsor organisation

Debiopharm International SA

Address

Forum Apres-Demain, Chemin Messidor 5-7 Chemin Messidor 5-7

City

Lausanne

Postcode

1006

Country

Switzerland

Scientific contact point

Organisation

Debiopharm International SA

Contact name

Debiopharm International S.A / Clinical department

Public contact point

Organisation

Debiopharm International SA

Contact name

Debiopharm International S.A / Clinical department

Third parties 7

Locations

7 EU/EEA countries · 27 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 58 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

9 submissions — initial application plus substantial / non-substantial modifications