A Randomized Phase III Study to Investigate the Efficacy and Safety of Alpha1H as a Neoadjuvant Therapy in Participants with Low- to Intermediate-Risk/Low-Grade Papillary Non-Muscle Invasive Bladder Cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Hamlet BioPharma AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Female Urogenital Diseases and Pregnancy Complications [C13], Diseases [C] - Male Urogenital Diseases [C12]

Decision date (initial)

2026-06-29

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Hamlet BioPharma AB

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

The primary objective is to determine whether neoadjuvant intravesical Alpha1H administered prior to standard TURBT-based management improves Event-Free Survival (EFS) compared with standard TURBT-based management alone in patients with low- to intermediate-risk NMIBC.

Secondary objectives 3

1. To evaluate the CR rate in the Alpha1H arm compared to SOC.
2. The tumor response to Alpha1H will be evaluated, based on change in tumor size and molecular response markers in the tumor compared to SOC, urine cytology pre- and post- Alpha1H treatment and pre- and cell shedding and molecular response markers post-treatment.
3. To evaluate the tissue accumulation of Alpha1H, safety and tolerability of Alpha1H, incidence and severity of treatment-emergent adverse events, and to evaluate quality of life based on Patient-Reported-Outcomes.

Conditions and MedDRA coding

Non-Muscle Invasive Papillary Bladder Cancer

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Signed and dated informed consent.
2. Patient with low- to intermediate-risk (in low and intermediate risk subgroup according to IBCG subclassification) non-muscle invasive papillary bladder cancer (NMIBC).
3. Male and female subjects, 18 years or older.
4. Negative pregnancy test in women of childbearing potential.
5. Women of childbearing potential must agree to use appropriate highly effective methods of contraception during the study in compliance with the protocol requirements; fertile men must refrain from donating sperm.
6. Patients should be able to keep the content of the bladder for two hours.

Exclusion criteria 14

1. Patient with non-papillary tumor appearance at the time of initial cystoscopy
2. Any concurrent illness that may render a participant ineligible or limit compliance with study requirements.
3. Previously enrolled in this trial.
4. Previous history of T1 or high-grade disease in recurrent tumors.
5. Patient with T1 or high-grade non-muscle invasive papillary bladder cancer (NMIBC).
6. Previous intravesical BCG immunotherapy.
7. Participants with any other cancer diagnosis within the last 5 years (except for skin basalioma).
8. Acute urinary tract infection requiring antibiotic treatment.
9. Prior radiotherapy or systemic chemotherapy.
10. WHO performance status 3 or 4.
11. Any other investigational agent or non-marketed product within one month prior to Visit 1 and during the trial.
12. Known active HIV infection, defined as detectable HIV viral load at screening.
13. Active hepatitis B virus (HBV) infection, defined as hepatitis B surface antigen (HBsAg) positivity with detectable HBV DNA at screening.
14. Active hepatitis C virus (HCV) infection, defined as anti-HCV antibody positivity with detectable HCV RNA at screening in a patient not on stable antiviral treatment.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Event-Free Survival is defined as the time from randomization to the earliest occurrence of: i) Recurrence of NMIBC (any grade or stage), ii) Progression to muscle-invasive bladder cancer (MIBC), iii) Development of metastatic bladder cancer, iv) Death from any cause

Secondary endpoints 10

1. CR rate in the Alpha1H arm compared to SOC.
2. Overall Survival in Alpha1H arm compared to SOC.
3. Tumor response to Alpha1H based on change in tumor size, cell numbers in urine, properties of shed tumor cells and induction of apoptosis.
4. Tumor response defined by cancer-related gene expression in tissue samples and urine RNA.
5. Protein biomarkers/immune response to Alpha1H in the urine of patients pre- and post-Alpha1H treatment.
6. Correlation between tumor cell shedding and recurrence or CR failure in study population.
7. Tissue accumulation of Alpha1H.
8. Safety and tolerability of Alpha1H.
9. Incidence and severity of treatment-emergent adverse events (AEs) and complications attributable to intravesical instillation of Alpha 1H (dysuria, urinary frequency/urgency, urinary retention, hematuria).
10. Quality of Life (QOL) changes based on Patient-Reported-Outcomes (QLQ-NMIBC24]) from baseline to follow-up visit.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Hamlet BioPharma AB

Sponsor organisation

Hamlet BioPharma AB

Address

S Allhelgonafors., Klinikgatan 32, Lunds Allhelgonafors. Klinikgatan 32 Lunds Allhelgonafors.

City

Lund

Postcode

222 42

Country

Sweden

Scientific contact point

Organisation

Hamlet BioPharma AB

Contact name

Catharina Svanborg

Public contact point

Organisation

Hamlet BioPharma AB

Contact name

Catharina Svanborg

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Results and documents

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

Documents 8 files

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

Application history

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