A 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

NCT07804056 | Recruiting Phase 3 FDA Drug

• 2 other identifiers: HP003-0012026-525531-16-00
• Study Type: interventional
• Target: 194
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to learn if the drug Alpha1H works to treat low-to-intermediate risk non-muscle-invasive bladder cancer in adults. It will also learn about the safety of drug Alpha1H. The main questions it aims to answer are:

• Does giving drug Alpha1H before surgery lower the risk of cancer returning or worsening compared to standard care alone?
• Is drug Alpha1H safe and well-tolerated by participants? Researchers will compare participants receiving drug Alpha1H before standard surgery to participants receiving standard care alone to see if drug Alpha1H lowers the risk of cancer returning or progressing. Participants will:
• Be randomly assigned to receive either drug Alpha1H before surgery or standard care alone.
• Receive drug Alpha1H directly into the bladder 6 times over about 1 month if assigned to the Alpha1H group.
• Hold the liquid in the bladder for up to 2 hours during each visit.
• Undergo standard surgery through the urethra (TURBT) to remove remaining tumor tissue.
• Visit the clinic regularly for follow-up checkups (including bladder examinations and urine tests) to check if the cancer returns.
• Fill out questionnaires about their quality of life.

Conditions

Urinary Bladder Neoplasms; Non-muscle Invasive Bladder Cancer (NMIBC)

Keywords

Non-Muscle Invasive Bladder Cancer; Papillary Bladder Carcinoma; Low-Grade Bladder Cancer; Low-Risk Bladder Cancer; Intermediate-Risk Bladder Cancer; Alpha1H; Neoadjuvant Therapy; Intravesical Instillation

Outcome Measures

Primary Outcomes (1)

• Event-Free Survival (EFS)

  From randomization until the occurrence of an EFS event or study completion, assessed at 3, 6, 9 (optional), and 12 months post-randomization, and every 6 months thereafter for up to 3 years.

Secondary Outcomes (7)

• Complete Response (CR) Rate

  Day 30 (±5 days), prior to TURBT

• Overall Survival (OS)

  From randomization through study completion (assessed at 3, 6, 9 [optional], and 12 months, and every 6 months thereafter for up to 3 years).

• Tumor Response (Morphological and Cellular)

  Baseline (Day 1) to Day 30 (±5 days)

• Tumor Gene Expression

  Baseline (Day 1) to Day 30 (±5 days)

• Urinary Biomarkers and Immune Response

  Day 1, 3, 5, 8, 15, and 22 (pre- and post-instillation), and Day 30 (±5 days)

Study Arms (2)

Alpha1H

EXPERIMENTAL

Participants receive 6 intravesical instillations of Alpha1H over approximately 1 month prior to transurethral resection of bladder tumor (TURBT).

Drug: Alpha1H; Procedure: Transurethral Resection of Bladder Tumor (TURBT); Drug: Intravesical Chemotherapy

Standard of Care

ACTIVE COMPARATOR

Participants receive standard of care consisting of transurethral resection of bladder tumor (TURBT) followed by a single early intravesical instillation of standard chemotherapy.

Procedure: Transurethral Resection of Bladder Tumor (TURBT); Drug: Intravesical Chemotherapy

Interventions

Alpha1H DRUG

Administered via intravesical instillation directly into the urinary bladder. Participants in the experimental group receive a total of 6 instillations on Days 1, 3, 5, 8, 15, and 22 over approximately 1 month prior to TURBT. During each treatment, participants are asked to retain the solution in the bladder for up to 2 hours.

Alpha1H

Transurethral Resection of Bladder Tumor (TURBT) PROCEDURE

Standard endoscopic surgical procedure performed through the urethra to resect and remove papillary bladder tumor tissue. Performed approximately 30 days after study entry (on Visit 8). Resected tumor tissue is collected for histopathology and central analysis.

Alpha1H; Standard of Care

Intravesical Chemotherapy DRUG

A single early intravesical instillation of standard-of-care chemotherapy (epirubicin, mitomycin, or gemcitabine) administered into the urinary bladder shortly following TURBT surgery in accordance with local institutional guidelines.

Alpha1H; Standard of Care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed and dated informed consent.
• Low- or intermediate-risk non-muscle-invasive bladder cancer (NMIBC) meeting one of the following definitions:
• Low-risk NMIBC: Primary, solitary, Ta, low-grade, 0.5 cm to 3 cm.
• Intermediate-risk NMIBC (low-to-intermediate risk subgroup per IBCG classification):
• Primary multifocal (\<10 lesions), Ta, low-grade, 0.5 cm to 3 cm;
• Recurrent solitary, Ta, low-grade, 0.5 cm to 3 cm; or
• Recurrent multifocal (\<10 lesions), Ta, low-grade, \>1 year after previous recurrence.
• Men and women aged 18 years or older.
• Negative pregnancy test at screening for women of childbearing potential.
• Women of childbearing potential must agree to use highly effective contraception methods throughout study participation; men of childbearing potential must refrain from donating sperm during the study.
• Ability to retain bladder contents for 2 hours.

You may not qualify if:

• Patient with non-papillary tumor appearance at the time of initial cystoscopy.
• Previous history of T1 or high-grade disease in recurrent tumors.
• Patients with T1 or high-grade non-muscle invasive papillary bladder cancer (NMIBC).
• Previous intravesical BCG immunotherapy.
• Patients with any other cancer diagnosis within the last 5 years (except for skin basalioma).
• Acute urinary tract infection requiring antibiotic treatment.
• Prior radiotherapy or systemic chemotherapy.
• WHO performance status of 3 or 4.
• Any other investigational agent or non-marketed product within one month prior to Visit 1 and during the trial.
• Known active HIV infection, defined as detectable HIV viral load at screening.
• Active hepatitis B virus (HBV) infection, defined as hepatitis B surface antigen (HBsAg) positivity with detectable HBV DNA at screening.
• 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.
• Any concurrent illness that may render a participant ineligible or limit compliance with study requirements.
• Previously enrolled in this trial.

Sponsors & Collaborators

• Hamlet Pharma AB: lead

Study Sites (1)

Fakultni nemocnice Motol a Homolka

Prague, 15000, Czechia

RECRUITING

MeSH Terms

Conditions

Urinary Bladder Neoplasms; Non-Muscle Invasive Bladder Neoplasms

Interventions

Transurethral Resection of Bladder

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Urologic Surgical Procedures; Urogenital Surgical Procedures; Surgical Procedures, Operative

Central Study Contacts

Catharina Svanborg, MD, PhD.

CONTACT

+46709426549; catharina.svanborg@med.lu.se

Petr Bouska

CONTACT

+420773076076; pe.bouska@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 26, 2026
• First Posted: September 4, 2026
• Study Start: September 17, 2026
• Primary Completion (Estimated): July 1, 2029
• Study Completion (Estimated): July 1, 2029
• Last Updated: September 21, 2026

Record last verified: 2026-09

Locations

CZ (1)