HPV-Induced Genital LesionsPhase 2NCT03334240
ICVT in HPV-induced Genital Lesions of Immunocompromised and Immunocompetent Patients
A Phase 2 study testing CLS003 in people with HPV-Induced Genital Lesions, run by Maruho Co., Ltd. at 1 site in Netherlands.
Trial summary
This study is intended to explore and evaluate the pharmacodynamics and clinical efficacy of the ionic contra-viral therapy CLS003 in immunocompromised and immunocompetent patients with benign and premalignant HPV-induced genital lesions Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HPV-Induced Genital Lesions
- What is being tested?
- CLS003
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 28 participants
- Where
- 1 siteNetherlands
- Study dates
- 5 Oct 2017to 30 Oct 2018
- Phase
- Phase 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
- Patients ≥ 18 years in general, stable good health (with the exception of the immunocompromised disorder) as per judgment of the investigator based upon the results of a medical history, physical examination, ECG, chemistry, hematology.
- In case of immunocompromised patients including but not limited to; patients receiving immunosuppressive therapy for any reason, patients with auto-immune disease, HIV patients, transplantation patients
- In case of genital warts patient group(s): have at least 3 genital warts (only applicable to Study Part 1)
- In case of vulvar HSIL: at least one lesion that can be accurately measured in at least one dimension with longest diameter ≥ 20 mm OR in 2 perpendicular dimensions that when multiplied together give a surface area ≥ 120 mm² (only applicable to Study Part 1)
- If female of childbearing potential, have a negative urine pregnancy test at Screening and Day 0, and is willing to use effective contraception during the study and 3 months afterwards (i.e. oral, implanted, injectable, IUD, diaphragm, condom, tubal ligation, abstinence, or are in a monogamous relationship with a partner who has had a vasectomy)
- Able to participate and willing to give written informed consent and to comply with the study restrictions
- Ability to communicate well with the investigator in the Dutch language
- Willing to refrain from using other topical products in the treatment area, or prohibited medications for the duration of the study
Who cannot join
- Significant, uncontrolled or unstable disease in any organ system as per judgment of the investigator (regardless of association with the immunosuppressing disorder/therapy), including but not limited to: psychiatric, neurologic, cardiovascular, pulmonary, gastrointestinal, hepatic, renal, endocrine, hematologic or respiratory disease
- Have used or received any topical genital wart treatment, cryotherapy, electrocoagulation, surgery in the treatment area within 28 days prior to enrolment
- Have used or received any topical vulvar HSIL treatment, laser therapy or surgery in the treatment area within 28 days prior to enrolment
- Have any current relevant skin infections in the treatment area other than genital warts (inclusively, but not limited to atopic dermatitis, lichen sclerosis, lichen planus or psoriasis)
- Have a known sensitivity to any of the investigational product ingredients, including digoxin and furosemide
- Participation in an investigational drug or device study within 3 months prior to screening or more than 4 times in the past year
- Loss or donation of blood over 500 mL within three months prior to screening.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 2, Randomized, Vehicle-controlled, Double-blind Study to Explore the Efficacy, Pharmacodynamics and Safety of Topical Ionic Contra-viral Therapy (ICVT) Comprised of Digoxin and Furosemide in HPV-induced Genital Lesions of Immunocompromised and Immunocompetent Patients
This study is intended to explore and evaluate the pharmacodynamics and clinical efficacy of the ionic contra-viral therapy CLS003 in immunocompromised and immunocompetent patients with benign and premalignant HPV-induced genital lesions
Read the detailed description
This study is intended to explore clinical efficacy and safety/tolerability of ICVT as a potential treatment for benign and premalignant HPV-induced genital lesions in immunocompetent and immunosuppressed patients. This includes 3 different patient populations: i) immunocompetent patients with anogenital warts (AGWs), ii) immunocompromised patients with anogenital warts and iii) immunocompromised patients with vulvar high grade squamous intraepithelial neoplasia (HSIL), formerly referred to as usual type vulvar intraepithelial neoplasia (uVIN). Since digoxin / furosemide ICVT's mode of action is in part independent of the immune system and directly targeted to eradicate the causative HPV, we hypothesize this therapy to be of value in this specific group of individuals.
- Conditions
- HPV-Induced Genital Lesions
- Being tested
- CLS003, Vehicle
- Keywords
- HPV, Digoxin, Furosemide, Vulvar HSIL
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CLS003Drug
CLS003
VehicleDrug
Vehicle
| Study group | Role | What they receive |
|---|---|---|
| CLS003 | Experimental | Digoxin and Furosemide topical formulation Receives: Drug: CLS003 |
| Vehicle | Placebo comparator | Inactive vehicle Receives: Drug: Vehicle |
What is being measured
The primary outcome is the main question the study is designed to answer.
Lesion (vulvar HSIL or wart) size reduction
Measured: Day 0, 21, 42, 84, 126, (Part 1 of study), Day 0, 28, 56, 140 (Part 2 of study)
Change in patient-reported outcomes
Measured: Through study completion, up to 20 weeks
HPV viral load assessment
Measured: Day 0, 21, 42, 84, 126, (Part 1 of study), Day 0, 28, 56, 140 (Part 2 of study)
Change in the HPV viral load
Measured: Day 0, 21, 42, 84, 126, (Part 1 of study), Day 0, 28, 56, 140 (Part 2 of study)
Mean HPV viral load
Measured: Day 0, 21, 42, 84, 126, (Part 1 of study), Day 0, 28, 56, 140 (Part 2 of study)
Histology (regression of vulvar HSIL or AGWs to no dysplasia, HPV genotyping)
Measured: Day 0, 42, 126, (Part 1 of study), Day 56 (Part 2 of study)
Local immunity status
Measured: Day 0, 21, 42, 84, 126, (Part 1 of study), Day 0, 28, 56, 140 (Part 2 of study)
Percentage clearance of vulvar HSIL lesions
For vulvar HSIL cohort
Measured: Day 0, 21, 42, 84, 126, (Part 1 of study), Day 0, 28, 56, 140 (Part 2 of study)
Proportion of patients with all vulvar HSIL lesions cleared
For vulvar HSIL cohort
Measured: Day 0, 21, 42, 84, 126, (Part 1 of study), Day 0, 28, 56, 140 (Part 2 of study)
Histology (regression of vulvar HSIL to no dysplasia)
For vulvar HSIL cohort
Measured: Day 0, 42, 126, (Part 1 of study), Day 56 (Part 2 of study)
Histological recurrence in the Part 1 follow-up period
For vulvar HSIL cohort
Measured: Day 84, 126
Percentage clearance of genital warts
For genital wart cohort
Measured: Day 0, 21, 42, 84, 126, (Part 1 of study), Day 0, 28, 56, 140 (Part 2 of study)
Proportion of patients with all genital warts cleared
For genital wart cohort
Measured: Day 0, 21, 42, 84, 126, (Part 1 of study), Day 0, 28, 56, 140 (Part 2 of study)
Clinical recurrence in the Part 1 follow-up period
For genital wart cohort
Measured: Day 84, 126
Secondary outcomes (1)
Adverse event collection to assess safety/tolerability of CLS003
Measured: Day 0, 21, 42, 84, 126, (Part 1 of study), Day 0, 28, 56, 140 (Part 2 of study), and as volunteered by patient
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Nov 2017
- Study start5 Oct 2017
- Primary completion30 Oct 2018
- Study completion30 Oct 2018
Why it stopped: Lack of effect in interim analysis
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HPV-Induced Genital LesionsStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- A total of 48 subjects are planned to be enrolled within one of the following three groups: a.) Immunocompetent patients with anogenital warts, b.) Immunocompromised with anogenital warts and c.) Immunocompromised with vulvar HSIL \[3:1, active/vehicle\]. Eligible subjects may enroll in an (up to) 8-week open-label Part 2 of study
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- Maruho Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- J. (Koos) Burggraaf, MD, PhD, Principal investigator, Centre For Human Drug Research
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03334240
- Sponsor's protocol ID
- CLS003-CO-PR-003
- Status last verified
- Mar 2019
- First submitted
- 30 Oct 2017
- Last updated
- 20 Mar 2019
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Randomized, Vehicle-controlled, Double-blind Study to Explore the Efficacy, Pharmacodynamics and Safety of Topical Ionic Contra-viral Therapy (ICVT) Comprised of Digoxin and Furosemide in HPV-induced Genital Lesions of Immunocompromised and Immunocompetent Patients
- ClinicalTrials.gov ID
- NCT03334240
- Acronym / sponsor ID
- CLS003-CO-PR-003
- Conditions
- HPV-Induced Genital Lesions
- Keywords
- HPV, Digoxin, Furosemide, Vulvar HSIL
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of effect in interim analysis
- Enrolment
- 28 participants (actual)
- Lead sponsor
- Maruho Co., Ltd.Industry (pharma, biotech, devices)
- Study start
- 5 Oct 2017 (actual)
- Primary completion
- 30 Oct 2018 (actual)
- Study completion
- 30 Oct 2018 (actual)
- First posted
- 7 Nov 2017 (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 is intended to explore and evaluate the pharmacodynamics and clinical efficacy of the ionic contra-viral therapy CLS003 in immunocompromised and immunocompetent patients with benign and premalignant HPV-induced genital lesions
Detailed description
This study is intended to explore clinical efficacy and safety/tolerability of ICVT as a potential treatment for benign and premalignant HPV-induced genital lesions in immunocompetent and immunosuppressed patients. This includes 3 different patient populations: i) immunocompetent patients with anogenital warts (AGWs), ii) immunocompromised patients with anogenital warts and iii) immunocompromised patients with vulvar high grade squamous intraepithelial neoplasia (HSIL), formerly referred to as usual type vulvar intraepithelial neoplasia (uVIN). Since digoxin / furosemide ICVT's mode of action is in part independent of the immune system and directly targeted to eradicate the causative HPV, we hypothesize this therapy to be of value in this specific group of individuals.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- A total of 48 subjects are planned to be enrolled within one of the following three groups: a.) Immunocompetent patients with anogenital warts, b.) Immunocompromised with anogenital warts and c.) Immunocompromised with vulvar HSIL [3:1, active/vehicle]. Eligible subjects may enroll in an (up to) 8-week open-label Part 2 of study
| Arm | Type | Receives |
|---|---|---|
| CLS003 | Experimental | Drug: CLS003Digoxin and Furosemide topical formulation |
| Vehicle | Placebo comparator | Drug: VehicleInactive vehicle |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Patients ≥ 18 years in general, stable good health (with the exception of the immunocompromised disorder) as per judgment of the investigator based upon the results of a medical history, physical examination, ECG, chemistry, hematology.
- In case of immunocompromised patients including but not limited to; patients receiving immunosuppressive therapy for any reason, patients with auto-immune disease, HIV patients, transplantation patients
- In case of genital warts patient group(s): have at least 3 genital warts (only applicable to Study Part 1)
- In case of vulvar HSIL: at least one lesion that can be accurately measured in at least one dimension with longest diameter ≥ 20 mm OR in 2 perpendicular dimensions that when multiplied together give a surface area ≥ 120 mm² (only applicable to Study Part 1)
- If female of childbearing potential, have a negative urine pregnancy test at Screening and Day 0, and is willing to use effective contraception during the study and 3 months afterwards (i.e. oral, implanted, injectable, IUD, diaphragm, condom, tubal ligation, abstinence, or are in a monogamous relationship with a partner who has had a vasectomy)
Key exclusion criteria (7 listed)
- Significant, uncontrolled or unstable disease in any organ system as per judgment of the investigator (regardless of association with the immunosuppressing disorder/therapy), including but not limited to: psychiatric, neurologic, cardiovascular, pulmonary, gastrointestinal, hepatic, renal, endocrine, hematologic or respiratory disease
- Have used or received any topical genital wart treatment, cryotherapy, electrocoagulation, surgery in the treatment area within 28 days prior to enrolment
- Have used or received any topical vulvar HSIL treatment, laser therapy or surgery in the treatment area within 28 days prior to enrolment
- Have any current relevant skin infections in the treatment area other than genital warts (inclusively, but not limited to atopic dermatitis, lichen sclerosis, lichen planus or psoriasis)
- Have a known sensitivity to any of the investigational product ingredients, including digoxin and furosemide
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 |
|---|---|---|
| CLS003CLS003 | Drug | CLS003 |
| VehicleVehicle | Drug | Vehicle |
Primary outcome
Lesion (vulvar HSIL or wart) size reduction
Time frame: Day 0, 21, 42, 84, 126, (Part 1 of study), Day 0, 28, 56, 140 (Part 2 of study)
Change in patient-reported outcomes
Time frame: Through study completion, up to 20 weeks
HPV viral load assessment
Time frame: Day 0, 21, 42, 84, 126, (Part 1 of study), Day 0, 28, 56, 140 (Part 2 of study)
Change in the HPV viral load
Time frame: Day 0, 21, 42, 84, 126, (Part 1 of study), Day 0, 28, 56, 140 (Part 2 of study)
Mean HPV viral load
Time frame: Day 0, 21, 42, 84, 126, (Part 1 of study), Day 0, 28, 56, 140 (Part 2 of study)
Histology (regression of vulvar HSIL or AGWs to no dysplasia, HPV genotyping)
Time frame: Day 0, 42, 126, (Part 1 of study), Day 56 (Part 2 of study)
Local immunity status
Time frame: Day 0, 21, 42, 84, 126, (Part 1 of study), Day 0, 28, 56, 140 (Part 2 of study)
Percentage clearance of vulvar HSIL lesions
Time frame: Day 0, 21, 42, 84, 126, (Part 1 of study), Day 0, 28, 56, 140 (Part 2 of study)
For vulvar HSIL cohort
Proportion of patients with all vulvar HSIL lesions cleared
Time frame: Day 0, 21, 42, 84, 126, (Part 1 of study), Day 0, 28, 56, 140 (Part 2 of study)
For vulvar HSIL cohort
Histology (regression of vulvar HSIL to no dysplasia)
Time frame: Day 0, 42, 126, (Part 1 of study), Day 56 (Part 2 of study)
For vulvar HSIL cohort
Histological recurrence in the Part 1 follow-up period
Time frame: Day 84, 126
For vulvar HSIL cohort
Percentage clearance of genital warts
Time frame: Day 0, 21, 42, 84, 126, (Part 1 of study), Day 0, 28, 56, 140 (Part 2 of study)
For genital wart cohort
Proportion of patients with all genital warts cleared
Time frame: Day 0, 21, 42, 84, 126, (Part 1 of study), Day 0, 28, 56, 140 (Part 2 of study)
For genital wart cohort
Clinical recurrence in the Part 1 follow-up period
Time frame: Day 84, 126
For genital wart cohort
1 secondary outcome
Adverse event collection to assess safety/tolerability of CLS003
Time frame: Day 0, 21, 42, 84, 126, (Part 1 of study), Day 0, 28, 56, 140 (Part 2 of study), and as volunteered by patient
Results and safety
The study was stopped early (reason given: Lack of effect in interim analysis). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Mar 2019.
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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.
J. (Koos) Burggraaf, MD, PhD principal investigator
Centre For Human Drug Research
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing CLS003 in people with HPV-Induced Genital Lesions, run by Maruho Co., Ltd. at 1 site in Netherlands.
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 8 inclusion and 7 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: stopped early, as of the sponsor's last update on 20 Mar 2019. 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 Netherlands. 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 phase mean?
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?
The study was stopped early (reason given: Lack of effect in interim analysis). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Lesion (vulvar HSIL or wart) size reduction (time frame: Day 0, 21, 42, 84, 126, (Part 1 of study), Day 0, 28, 56, 140 (Part 2 of study)). The study lists 14 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 20 Mar 2019.