A First-in-Human Study of alpha1H in Patients With Non-muscle Invasive Bladder Cancer

NCT03560479 | Unknown Phase 1

• 2 other identifiers: HP002-0012016-004269-14
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

Brief Summary

This study evaluates the tolerability and preliminary anti-tumour effect of alpha1H in adults with non-muscle invasive bladder cancer, who are awaiting transurethral surgery. In the main, blinded part of the study, one group of subjects will receive treatment with alpha1H and the other half will receive placebo. In a second, dose-escalation part of the study, a third and fourth group of subjects will receive increased doses of alpha1H. The treatment is given on 6 occasions during a period of 22 days. The study duration is 8 - 12 weeks including scheduled follow-up and up to 27 months when an optional 24-months non-interventional follow-up period is included.

Conditions

Non-muscle Invasive Bladder Cancer

Keywords

First-in human; Phase 1; Phase 2; Safety; Tolerability; Cancer; Bladder cancer; Clinical trial; Anti-cancer; Antineoplastic; alpha1H; HAMLET; Urothelial; Malignant; Papillary; Transurethral; Non-muscle invasive; Instillation; Intravesical

Outcome Measures

Primary Outcomes (3)

• Safety as Adverse Events Profile

  Incidence of adverse events and classification in terms of severity, causality and outcome

  From signing of informed consent (Day 1) and until 30 days after the last dose (Day 52).

• Efficacy as Cell Shedding

  Change in cell shedding into urine (number of epithelial cells per mL of urine).

  Days 1 to 22

• Change from baseline in characteristics of papillary tumors

  The bladder tumors will be characterised by in vivo imaging during examination by cystoscopy.

  Prior to treatment (Baseline) and on Day 30, in connection with scheduled surgery.

Study Arms (4)

alpha1H, 7.4 mg/mL

EXPERIMENTAL

alpha1H (7.4 mg/mL), solution for instillation, 30 mL

Drug: alpha1H, 7.4 mg/mL

placebo

PLACEBO COMPARATOR

Placebo, 0.9% NaCl (sodium chloride), 30 mL

Other: placebo

alpha1H, 37 mg/mL

EXPERIMENTAL

alpha1H (37 mg/mL), solution for instillation, 30 mL

Drug: alpha1H, 37 mg/mL

alpha1H, 74 mg/mL

EXPERIMENTAL

alpha1H (74 mg/mL), solution for instillation, 30 mL

Drug: alpha1H, 74 mg/mL

Interventions

alpha1H, 74 mg/mL DRUG

Intravesical instillations on 6 occasions during 22 days (Days 1, 3, 5, 8, 15 and 22)

alpha1H, 74 mg/mL

placebo OTHER

Intravesical instillations on 6 occasions during 22 days (Days 1, 3, 5, 8, 15 and 22)

placebo

alpha1H, 37 mg/mL DRUG

Intravesical instillations on 6 occasions during 22 days (Days 1, 3, 5, 8, 15 and 22)

alpha1H, 37 mg/mL

Eligibility Criteria

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

You may qualify if:

• Patient with non-muscle invasive papillary bladder cancer (NMIBC) based on cystoscopy appearance, on the waiting list for TURB.
• Negative pregnancy test in women of childbearing potential.
• Appropriate methods of contraception in women of childbearing potential during study.
• Patients should be able to keep the content of the bladder for at least one hour.

You may not qualify if:

• Patient with a previous history of muscle invasive bladder cancer.
• Patient with a history of NMIBC with an interval shorter than 6 months after previous TURB.
• Previous intravesical Bacillus Calmette-Guerin (BCG) immunotherapy in the last 12 months.
• Previous intravesical chemotherapy in the last 12 months.
• Participants with any other cancer diagnosis within the last 5 years (except of skin basaliomas).
• Acute urinary tract infection
• Participants with prior radiotherapy or systemic chemotherapy.
• Participants receiving any other investigational agent or non-marketed product one month prior to Visit 1 and during the trial.
• 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)

Motol University Hospital

Prague, Czechia

RECRUITING

Related Publications (1)

• Brisuda A, Ho JCS, Kandiyal PS, Ng JT, Ambite I, Butler DSC, Hacek J, Wan MLY, Tran TH, Nadeem A, Tran TH, Hastings A, Storm P, Fortunati DL, Esmaeili P, Novotna H, Hornak J, Mu YG, Mok KH, Babjuk M, Svanborg C. Bladder cancer therapy using a conformationally fluid tumoricidal peptide complex. Nat Commun. 2021 Jun 8;12(1):3427. doi: 10.1038/s41467-021-23748-y.

  PMID: 34103518 DERIVED

MeSH Terms

Conditions

Non-Muscle Invasive Bladder Neoplasms; Neoplasms; Urinary Bladder Neoplasms

Condition Hierarchy (Ancestors)

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

Study Officials

• Marek Babjuk, MD, Prof.

  Motol University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Catharina Svanborg, Prof.

CONTACT

+4640122505; catharina.svanborg@med.lu.se

Mats Persson, PhD

CONTACT

+4640122500; mats.persson@hamletpharma.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Part 1 (Main part): Patients are randomized to receive intravesical instillations of either alpha1H (7.4 mg/mL) or placebo. The randomization ratio is 1:1. Part 2 (DE part): In this open part of the study, two groups of patients will receive escalating doses of alpha1H in a standard 3+3 design. One group will receive a dose of 37 mg/mL and, if tolerated, one group will receive a dose of 74 mg/mL.

Study Record Dates

• First Submitted: May 24, 2018
• First Posted: June 18, 2018
• Study Start: May 21, 2018
• Primary Completion: December 1, 2021
• Study Completion: December 1, 2023
• Last Updated: August 19, 2020

Record last verified: 2020-08

Locations

CZ (1)