Non-muscle Invasive Bladder CancerPhase 1/2NCT03560479
A First-in-Human Study of alpha1H in Patients With Non-muscle Invasive Bladder Cancer
A Phase 1/2 study testing alpha1H, 7.4 mg/mL, alpha1H, 37 mg/mL and alpha1H, 74 mg/mL in people with Non-muscle Invasive Bladder Cancer, run by Hamlet Pharma AB at 1 site in Czechia.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-muscle Invasive Bladder Cancer
- What is being tested?
- alpha1H, 7.4 mg/mL, alpha1H, 37 mg/mL and alpha1H, 74 mg/mL
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 52 participants
- Where
- 1 siteCzechia
- Study dates
- 21 May 2018to Dec 2023
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 10Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
Czechia1 site, 1 recruiting
- Recruiting
Motol University Hospital
Prague
Marek Babjuk, MD, Prof
About this study
Official title: A Randomized Placebo Controlled Phase I/II Study Evaluating the Safety and Efficacy of alpha1H in Adult Patients With Non-muscle Invasive Bladder Cancer Awaiting Transurethral Surgery
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.
Read the detailed description
Protein-lipid complexes represent a new type of tumouricidal biologicals, with broad effects against cancers of different origins. The investigational product alpha1H is a synthetic peptide, corresponding to the alpha1 domain of α-lactalbumin, in complex with oleic acid. Alpha1H is a further development product of HAMLET, a complex between human alpha-lactalbumin and oleic acid, which has shown broad anti-tumor activity with a high degree of selectivity.
This study is a combined phase 1/2, placebo controlled, double blind study in subjects with non-muscle invasive bladder cancer awaiting transurethral resection of bladder (TURB). The first, main part of the study is randomized 1/1 and the subjects will receive intravesical instillation of either alpha1H or placebo on 6 occasions during a period of 22 days (on days 1, 3, 5, 8, 15 and 22). In a second, open, dose-escalation (DE) part of the study, two additional groups will receive increased doses of alpha1H in a standard 3+3 design in order to determine a Maximum Tolerated Dose (MTD) or alternatively, a Maximum Administered Dose (MAD). The same treatment schedule as in part 1 will be followed. One group will receive a dose of 5 times the original dose and, if tolerated, the last group will receive a dose of 10 times the original dose.
Cell shedding is quantified and characterized at each treatment occasion. The bladder tumors are characterized prior treatment and prior to the scheduled surgery. Remaining tumors will be removed by TURB (according to European Association of Urology (EAU) Guidelines recommendations) and tissues will be obtained for analyses.
A follow-up Visit will take place 30 days after the last administration of study treatment.
The total study duration of the main study is 8 - 12 weeks. After the main study, the subjects may continue in an optional extended 24-months follow-up period.
- Conditions
- Non-muscle Invasive Bladder Cancer
- Being tested
- alpha1H, 7.4 mg/mL, placebo, alpha1H, 37 mg/mL, alpha1H, 74 mg/mL
- 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
- Medical subject headings
- Non-Muscle Invasive Bladder Neoplasms, Neoplasms, Urinary Bladder Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
alpha1H, 7.4 mg/mLDrug
Intravesical instillations on 6 occasions during 22 days (Days 1, 3, 5, 8, 15 and 22)
placeboOther
Intravesical instillations on 6 occasions during 22 days (Days 1, 3, 5, 8, 15 and 22)
alpha1H, 37 mg/mLDrug
Intravesical instillations on 6 occasions during 22 days (Days 1, 3, 5, 8, 15 and 22)
alpha1H, 74 mg/mLDrug
Intravesical instillations on 6 occasions during 22 days (Days 1, 3, 5, 8, 15 and 22)
| Study group | Role | What they receive |
|---|---|---|
| alpha1H, 7.4 mg/mL | Experimental | alpha1H (7.4 mg/mL), solution for instillation, 30 mL Receives: Drug: alpha1H, 7.4 mg/mL |
| placebo | Placebo comparator | Placebo, 0.9% NaCl (sodium chloride), 30 mL Receives: Other: placebo |
| alpha1H, 37 mg/mL | Experimental | alpha1H (37 mg/mL), solution for instillation, 30 mL Receives: Drug: alpha1H, 37 mg/mL |
| alpha1H, 74 mg/mL | Experimental | alpha1H (74 mg/mL), solution for instillation, 30 mL Receives: Drug: alpha1H, 74 mg/mL |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety as Adverse Events Profile
Incidence of adverse events and classification in terms of severity, causality and outcome
Measured: 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).
Measured: 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.
Measured: Prior to treatment (Baseline) and on Day 30, in connection with scheduled surgery.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jun 2018
- Study start21 May 2018
- Primary completionDec 2021 (estimated)
- Study completionDec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Non-muscle Invasive Bladder CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 52 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hamlet Pharma AB
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Marek Babjuk, MD, Prof., Principal investigator, Motol University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03560479
- Sponsor's protocol ID
- HP002-001
- Other IDs
- 2016-004269-14, 2016
- Status last verified
- Aug 2020
- First submitted
- 24 May 2018
- Last updated
- 19 Aug 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Haq F, Chinchankar S, Ambite I, Ahmadi S, Tran H, Nazari A, Brisuda A, Hacek J, Babjuk M, Svanborg C. Identification of alpha1-oleate as a potent regulator of adipokine-dependent metabolism, in bladder cancer tissue. Cancer Metab. 2026 Jun 23;14(1):21. doi: 10.1186/s40170-026-00445-2.
PubMed 42337683Ahmadi S, Ambite I, Brisuda A, Hacek J, Haq F, Sabari S, Vanarsa K, Mohan C, Babjuk M, Svanborg C. Similar immune responses to alpha1-oleate and Bacillus Calmette-Guerin treatment in patients with bladder cancer. Cancer Med. 2024 Apr;13(7):e7091. doi: 10.1002/cam4.7091.
PubMed 38553868Brisuda 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.
PubMed 34103518
Study at a glance
From the registry record, last updated by the sponsor on 19 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Placebo Controlled Phase I/II Study Evaluating the Safety and Efficacy of alpha1H in Adult Patients With Non-muscle Invasive Bladder Cancer Awaiting Transurethral Surgery
- ClinicalTrials.gov ID
- NCT03560479
- Acronym / sponsor ID
- HP002-001
- Conditions
- Non-muscle Invasive Bladder Cancer
- Keywords
- First-in human, Phase 1, Phase 2, Safety, Tolerability, Cancer, Bladder cancer, Clinical trial
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 52 participants (estimated)
- Lead sponsor
- Hamlet Pharma ABIndustry (pharma, biotech, devices)
- Study start
- 21 May 2018 (actual)
- Primary completion
- Dec 2021 (estimated)
- Study completion
- Dec 2023 (estimated)
- First posted
- 18 Jun 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Protein-lipid complexes represent a new type of tumouricidal biologicals, with broad effects against cancers of different origins. The investigational product alpha1H is a synthetic peptide, corresponding to the alpha1 domain of α-lactalbumin, in complex with oleic acid. Alpha1H is a further development product of HAMLET, a complex between human alpha-lactalbumin and oleic acid, which has shown broad anti-tumor activity with a high degree of selectivity.
This study is a combined phase 1/2, placebo controlled, double blind study in subjects with non-muscle invasive bladder cancer awaiting transurethral resection of bladder (TURB). The first, main part of the study is randomized 1/1 and the subjects will receive intravesical instillation of either alpha1H or placebo on 6 occasions during a period of 22 days (on days 1, 3, 5, 8, 15 and 22). In a second, open, dose-escalation (DE) part of the study, two additional groups will receive increased doses of alpha1H in a standard 3+3 design in order to determine a Maximum Tolerated Dose (MTD) or alternatively, a Maximum Administered Dose (MAD). The same treatment schedule as in part 1 will be followed. One group will receive a dose of 5 times the original dose and, if tolerated, the last group will receive a dose of 10 times the original dose.
Cell shedding is quantified and characterized at each treatment occasion. The bladder tumors are characterized prior treatment and prior to the scheduled surgery. Remaining tumors will be removed by TURB (according to European Association of Urology (EAU) Guidelines recommendations) and tissues will be obtained for analyses.
A follow-up Visit will take place 30 days after the last administration of study treatment.
The total study duration of the main study is 8 - 12 weeks. After the main study, the subjects may continue in an optional extended 24-months follow-up period.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| alpha1H, 7.4 mg/mL | Experimental | Drug: alpha1H, 7.4 mg/mLalpha1H (7.4 mg/mL), solution for instillation, 30 mL |
| placebo | Placebo comparator | Other: placeboPlacebo, 0.9% NaCl (sodium chloride), 30 mL |
| alpha1H, 37 mg/mL | Experimental | Drug: alpha1H, 37 mg/mLalpha1H (37 mg/mL), solution for instillation, 30 mL |
| alpha1H, 74 mg/mL | Experimental | Drug: alpha1H, 74 mg/mLalpha1H (74 mg/mL), solution for instillation, 30 mL |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (10 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| alpha1H, 7.4 mg/mLIntravesical instillations on 6 occasions during 22 days (Days 1, 3, 5, 8, 15 and 22) | Drug | alpha1H, 7.4 mg/mL |
| placeboIntravesical instillations on 6 occasions during 22 days (Days 1, 3, 5, 8, 15 and 22) | Other | placebo |
| alpha1H, 37 mg/mLIntravesical instillations on 6 occasions during 22 days (Days 1, 3, 5, 8, 15 and 22) | Drug | alpha1H, 37 mg/mL |
| alpha1H, 74 mg/mLIntravesical instillations on 6 occasions during 22 days (Days 1, 3, 5, 8, 15 and 22) | Drug | alpha1H, 74 mg/mL |
Primary outcome
Safety as Adverse Events Profile
Time frame: From signing of informed consent (Day 1) and until 30 days after the last dose (Day 52).
Incidence of adverse events and classification in terms of severity, causality and outcome
Efficacy as Cell Shedding
Time frame: Days 1 to 22
Change in cell shedding into urine (number of epithelial cells per mL of urine).
Change from baseline in characteristics of papillary tumors
Time frame: Prior to treatment (Baseline) and on Day 30, in connection with scheduled surgery.
The bladder tumors will be characterised by in vivo imaging during examination by cystoscopy.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Aug 2020.
- Derived from this study: PubMed 42337683Haq F, Chinchankar S, Ambite I, Ahmadi S, Tran H, Nazari A, Brisuda A, Hacek J, Babjuk M, Svanborg C. Identification of alpha1-oleate as a potent regulator of adipokine-dependent metabolism, in bladder cancer tissue. Cancer Metab. 2026 Jun 23;14(1):21. doi: 10.1186/s40170-026-00445-2.
- Derived from this study: PubMed 38553868Ahmadi S, Ambite I, Brisuda A, Hacek J, Haq F, Sabari S, Vanarsa K, Mohan C, Babjuk M, Svanborg C. Similar immune responses to alpha1-oleate and Bacillus Calmette-Guerin treatment in patients with bladder cancer. Cancer Med. 2024 Apr;13(7):e7091. doi: 10.1002/cam4.7091.
- Derived from this study: PubMed 34103518Brisuda 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marek Babjuk, MD, Prof. principal investigator
Motol University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing alpha1H, 7.4 mg/mL, alpha1H, 37 mg/mL and alpha1H, 74 mg/mL in people with Non-muscle Invasive Bladder Cancer, run by Hamlet Pharma AB at 1 site in Czechia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 19 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Czechia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Catharina Svanborg, Prof. (+4640122505, catharina.svanborg@med.lu.se), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety as Adverse Events Profile (time frame: From signing of informed consent (Day 1) and until 30 days after the last dose (Day 52).). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03560479, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Aug 2020.