Nadofaragene firadenovec for Non-muscle invasive bladder cancer (intermediate risk)

Inclusion criteria

• {"criterion_text":"- Willing and able to provide written consent for the trial, obtained prior to any trial-related procedures"}
• {"criterion_text":"- Subjects with prostate cancer which has previously been treated with radiation therapy are eligible, if the radiation therapy was complete at least 1 years prior to randomization and the subject has remained disease free"}
• {"criterion_text":"- Female subjects of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of investigational medicinal product (IMP). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required"}
• {"criterion_text":"- Females of reproductive potential must meet 1 of the following conditions:  Have a negative highly sensitive urine or serum pregnancy test upon entry into this trial and be willing to use highly effective contraceptiona during treatment with the IMP and for 6 months following the last dose. For sites in Japan only, contraception should be approved in Japan.  Be postmenopausal (no menstrual period for a minimum of 12 months, as confirmed by follicle-stimulating hormone levels). For sites in Japan only, postmenopausal women should be 45 years or older.  Be surgically sterileb . a Highly effective methods of contraception include: combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal or transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable or implantable), intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomised partner, and sexual abstinence. Vasectomised partner is a highly effective birth control method provided that partner is the sole sexual partner of the female subject and that the vasectomised partner has received medical assessment of the surgical success. Sexual abstinence is defined as refraining from heterosexual intercourse. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject. b The methods acceptable for surgical sterility are hysterectomy, bilateral salpingectomy, and bilateral oophorectomy."}
• {"criterion_text":"- Male subjects must be willing to use a male condom and effective contraception during sex throughout the treatment period and for 3 months following the last dose. Effective contraception is defined in inclusion criterion 12."}
• {"criterion_text":"- Adequate laboratory values defined as:  Hemoglobin ≥9 g/dL, without transfusion or erythropoietin dependency  White blood cells (WBC) ≥4 x 109 /L  Absolute neutrophil count (ANC) ≥1.5 x 109 /L  Platelets ≥75 x 109 /L  International Normalised Ratio (INR) or Prothrombin Time (PT) and Activated Partial Thromboplastin Time (aPTT) ≤1.5 x upper limit of normal (ULN), unless subject is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants  Aspartate aminotransferase (AST) ≤1.5 x ULN  Alanine aminotransferase (ALT) ≤1.5 x ULN  Total bilirubin ≤1.5 x ULN  Calculated creatinine clearance ≥30ml/min  Estimated glomerular filtration rate (eGFR) ≥30ml/min/1.73m2 Inclusion criteria 3 and 4 are considered key."}
• {"criterion_text":"- Age 18 years or older at the time of consent"}
• {"criterion_text":"- Newly diagnosed or recurrent intermediate risk (IR) non-muscle invasive bladder cancer (NMIBC) at screening as defined by American Urological Association (AUA)/Society of Urologic Oncology [SUO] Guideline (2020)"}
• {"criterion_text":"- Has undergone complete transurethral resection of bladder tumor (TURBT; with or without peri-operative intravesical chemotherapy) within 60 days prior to randomization, with 1 of the following confirmed by a diagnostic pathology report (which should indicate whether lamina propria and muscularis propria are present as well as the degree of involvement, if presenta ):  Low-grade Ta, <12 months  Low-grade Ta, solitary and >3 cm  Low-grade Ta, multifocalb  High-grade Ta, solitary and ≤3 cm  Low-grade T1a,b a Patients with T1 disease should undergo resection at the base of the lesion and biopsies should contain muscle fibres. b Restage TURBT may be done at the discretion of the investigator."}
• {"criterion_text":"- Must adhere to applicable (regional or national) policies and procedures for the management and control of COVID-19"}
• {"criterion_text":"- Life expectancy of >2 years"}
• {"criterion_text":"- Have a normal upper urinary tract (as evidenced by ultrasound, computed tomography (CT) urography or other appropriate test within 1 year prior to randomization) and no evidence of tumor in prostatic urethra"}
• {"criterion_text":"- Eastern Cooperative Oncology Group (ECOG) status of 2 or less"}
• {"criterion_text":"- Subjects with prostate cancer on active surveillance at low risk for progression, defined as prostate-specific antigen (PSA) <10 ng/mL, Gleason score 6 and cT1 are permitted to be included into the trial at the discretion of the investigator"}

Exclusion criteria

• {"criterion_text":"- Current or previous evidence of muscle invasive (muscularis propria) or metastatic disease presented at the screening visit"}
• {"criterion_text":"- Has an active or intractable infection requiring systemic therapy"}
• {"criterion_text":"- Clinically significant and unexplained elevated liver tests"}
• {"criterion_text":"- Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening until 6 months (females) or 3 months (males) after the last IMP dose"}
• {"criterion_text":"- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject’s participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator"}
• {"criterion_text":"- Has a known additional malignancy that is progressing or requires active treatment. Exceptions include: • Prior malignancy that has not progressed nor required active treatment in the past 2 years • Basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer"}
• {"criterion_text":"- Cannot hold instillation for 1 hour"}
• {"criterion_text":"- Any intravesical therapy within 8 weeks prior to randomization, except any of the following: mitomycin C, doxorubicin, gemcitabine, epirubicin, or pirarubicin, when administered as a single peri-operative intravesical instillation immediately following or within 24 hours after TURBT pre-trial or during screening (pre-trial/screening TURBT)"}
• {"criterion_text":"- Any adjuvant pre-trial intravesical therapy more than 8 weeks prior to randomization, except any of the following:  Peri-operative single instillation intravesical therapy related to a prior occurrence(s) of NMIBC  1 intravesical chemotherapy induction course (once weekly for 6 weeks) related to a prior occurrence of NMIBC administered within 12 months prior to pre-trial/screening TURBT  1 intravesical induction course of BCG (once weekly for 5-6 weeks) related to a prior occurrence of NMIBC administered within 12 months prior to pre-trial/screening TURBT"}
• {"criterion_text":"- Any pre-trial adjuvant intravesical therapy > 8 weeks prior to beginning trial treatment, including induction and maintenance therapy, except any of the following: • 1 intravesical chemotherapy induction course (once weekly for 6 weeks) related to a prior occurrence of NMIBC administered within 12 months prior to screening TURBT • 1 intravesical induction course of BCG (once weekly for 5-6 weeks) related to a prior occurrence of NMIBC administered within 12 months prior to screening TURBT"}
• {"criterion_text":"- Prior or current investigational therapy for NMIBC within 28 days or randomization"}
• {"criterion_text":"- High-risk NMIBC defined as: • High-grade T1 • Any recurrent, high-grade Ta • High-grade Ta >3 cm (or multifocal) • Any carcinoma in situ (CIS) • Any Bacillus Calmette-Guérin (BCG) failure in high-grade subject • Any variant histology • Any prostatic urethral involvement"}
• {"criterion_text":"- Immunocompromised persons, including those receiving immunosuppressant therapy, may be at risk for disseminated adenovirus infection because of the possible presence of low levels of replication-competent adenovirus in nadofaragene firadenovec. Individuals who are immunosuppressed or immune-deficient should not come into contact with nadofaragene firadenovec."}
• {"criterion_text":"- Has active uncontrolled clinically significant cardiovascular disease"}
• {"criterion_text":"- Has known active Hepatitis B (e.g. HbsAg reactive) or Hepatitis C (e.g. Hepatitis C virus ribonucleic acid [qualitative] is detected)"}
• {"criterion_text":"- Has a known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the trial"}
• {"criterion_text":"- Concomitant participation in any other interventional studies, in which subject has received trial treatment (or used an investigation device), within 28 days of randomization"}
• {"criterion_text":"- Low-risk NMIBC defined as: • First occurrence of low-grade solitary Ta ≤3 cm • Recurrence of low-grade solitary Ta ≤3 cm >12 months from previous occurrence • Papillary urothelial neoplasm of low malignant potential"}
• {"criterion_text":"- Current systemic therapy for bladder cancer"}
• {"criterion_text":"- Has significant urinary incontinence or known bladder instability"}
• {"criterion_text":"- Current or prior pelvic external beam radiotherapy within 1 year of randomization"}
• {"criterion_text":"- Use of other adenoviral vector-based medication, e.g. COVID-19 vaccines, within 2 weeks before and after IMP instillation"}
• {"criterion_text":"- Current or prior use of nadofaragene firadenovec"}
• {"criterion_text":"- Suspected hypersensitivity to interferon-α2b"}

Primary endpoints

• {"endpoint_text":"- The primary endpoint is recurrence-free survival (RFS), defined as the time from the date of randomization to first documented recurrence or progression (as defined in the below table), or death (due to any cause), whichever occurs first during the treatment period (24 months).","definition_or_measurement_approach":"Recurrence-free survival (RFS) measured as time from randomization to first documented recurrence or progression (per protocol definitions) or death from any cause, assessed during the 24-month treatment period; summarised by hazard ratio comparing nadofaragene firadenovec versus observation."}

Methods

• Patient brochure (country-specific versions: DK, CZ, PL, ES, FR, IT) — printed brochure for patients to inform about the study and participation.
• Dr to patient letter (doctor-to-patient letters) — materials to be provided by clinicians to potential participants (country-specific versions).
• PAG materials / clinical study listing (PAG) — study listing and FAQs prepared for patient advocacy groups / patient audiences (country-specific PAG materials).
• Email blasts / to-patient email — electronic outreach to patients via email (country-specific templates: enewsletter content, email blast).
• Poster with flyer — printed posters and accompanying flyers for site display to recruit patients (country-specific versions).
• Patient video script — scripted content for patient-facing videos to explain the study (country-specific).
• Study-specific website / 'Find a site on website' materials — online method to direct patients to participating sites (country-specific materials).
• Patient FAQ sheet — documents to address frequently asked questions from patients (country-specific versions).
• GP letter (Italy specific) — materials to inform general practitioners about the study to facilitate referral.

Denmark

Earliest CTIS Part Ii Submission Date

17-03-2025

Latest Decision Or Authorization Date

17-10-2025

Processing Time Days

214

Number Of Sites

1

Number Of Participants

8

Czechia

Earliest CTIS Part Ii Submission Date

12-02-2026

Latest Decision Or Authorization Date

09-03-2026

Processing Time Days

25

Number Of Sites

4

Number Of Participants

18

Poland

Earliest CTIS Part Ii Submission Date

16-02-2026

Latest Decision Or Authorization Date

13-03-2026

Processing Time Days

25

Number Of Sites

3

Number Of Participants

15

Spain

Earliest CTIS Part Ii Submission Date

03-03-2025

Latest Decision Or Authorization Date

22-12-2025

Processing Time Days

294

Number Of Sites

12

Number Of Participants

199

France

Earliest CTIS Part Ii Submission Date

20-01-2025

Latest Decision Or Authorization Date

16-01-2026

Processing Time Days

361

Number Of Sites

12

Number Of Participants

46

Italy

Earliest CTIS Part Ii Submission Date

16-02-2026

Latest Decision Or Authorization Date

16-03-2026

Processing Time Days

28

Number Of Sites

2

Number Of Participants

10

Primary sponsor

Full Name

Ferring Pharmaceuticals A/S

Organisation Type

Pharmaceutical company

Country Of Registered Address

Denmark

Contract research organisations

Name

Syneos Health Netherlands B.V.

Responsibilities

Clinical operations; contact email sm_clinopsams@syneoshealth.com; phone +312003018500. Duties codes: 1,12,5

Third parties

• {"country":"Netherlands","full_name":"Syneos Health Netherlands B.V.","duties_or_roles":"Sponsor duties codes: 1, 12, 5 (as listed in CTIS thirdParty sponsorDuties)","organisation_type":"Pharmaceutical company"}