nadofaragene firadenovec for Non-muscle-invasive bladder cancer (high-grade, BCG-unresponsive) | Carcinoma in situ (bladder)

Inclusion criteria

• {"criterion_text":"- Signed informed consent obtained before beginning any trial-related procedures\n- Subjects with prostate cancer on active surveillance at low risk for progression are permitted to be included into the trial at the discretion of the investigator (see exclusion criterion 16)\n- Females of reproductive potential must have a negative highly sensitive urine or serum pregnancy test upon entry into this trial and be willing to use highly effective contraception during treatment with the investigational medicinal product (IMP) and for 6 months following the last dose. Otherwise, female subjects must be post-menopausal (no menstrual period for a minimum of 12 months, as confirmed by follicle-stimulating hormone levels) or surgically sterile. • 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.\n- Male subjects must use highly effective contraception and a condom during sexual contact regardless of partner’s childbearing potential, until 3 months following the last trial drug administration. Effective contraception is specified in inclusion criterion 11.\n- Adequate laboratory values: • Haemoglobin ≥10 g/dL • White blood cells (WBC) ≥3800/µL • Absolute neutrophil count (ANC) ≥2000/µL • Platelet count ≥100,000/µL • International normalised ratio (INR)a below institutional upper limit of normal (ULN) • Activated partial thromboplastin time (aPTT)a below institutional ULN • Aspartate aminotransferase (AST) ≤1.5 x ULN • Alanine aminotransferase (ALT) ≤1.5 x ULN • Total bilirubin ≤1.5 x ULN • Estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2 a It is accepted that subjects receiving anticoagulation therapy would not have INR and aPTT results that fall within ‘normal limits’. It is not intended to exclude these subjects and therefore medical discretion is permitted for subjects who have clinically acceptable results in regard to their current concomitant anticoagulant therapy.\n- Diagnosed, as documented, with carcinoma in situ (CIS) ±Ta/T1 high-grade disease • For T1 disease biopsies should contain muscle fibres\n- Unresponsive to ≥2 courses of Bacillus Calmette-Guerin (BCG) therapy within the last 12 months. BCG-unresponsive refers to subjects with high-grade non-muscle-invasive bladder cancer (NMIBC) who are unlikely to benefit from and who will not be receiving further intravesical BCG. The term “BCG-unresponsive” includes subjects who did not respond to BCG treatment and have a persistent high-grade recurrence within 12 months after BCG was initiated, and those who despite an initial complete response (CR) to BCG, relapse with CIS within 12 months of their last intravesical treatment with BCG or relapse with high grade Ta/T1 NMIBC within 6 months of their last intravesical treatment with BCG. The following criteria define the subjects who may be included in the trial: • Have received at least 2 courses of BCG within a 12-month period – defined as at least 5 of 6 induction BCG instillations and at least 2 of 3 instillations of maintenance BCG, or at least 2 of 6 instillations of a second induction course, where maintenance BCG is not given. o Exception: those who have T1 high-grade disease at 1st evaluation after induction BCG alone (at least 5 of 6 doses) may qualify in the absence of disease progression • At the time of tumour recurrence, subjects with CIS alone or high-grade Ta/T1 with CIS should be within 12 months of last exposure to BCG • No maximum limit to the amount of BCG administered • All visible papillary tumours must be resected and those with persistent T1 disease on transurethral resection of bladder tumour (TURBT) should undergo an additional re TURBT within 14 to 70 days prior to beginning trial treatment. Obvious areas of CIS should also be fulgurated\n- Eastern Cooperative Oncology Group (ECOG) status ≤2\n- Aged ≥18 years at the time of consent\n- Available for the whole duration of the trial\n- Life expectancy >2 years, in the opinion of the investigator\n- Absence of concomitant upper tract urothelial carcinoma or urothelial carcinoma within the prostatic urethra. Freedom from upper tract disease (if clinically indicated) as indicated by no evidence of upper tract tumour by either intravenous pyelogram, retrograde pyelogram, computed tomography (CT) scan with or without urogram, or magnetic resonance imaging (MRI) with or without urogram performed within 6 months of enrolment. Absence of locally advanced disease as assessed by CT scan or MRI\n- Subjects who elect not to undergo cystectomy"}

Exclusion criteria

• {"criterion_text":"- Current or previous evidence of muscle-invasive (muscularis propria) or metastatic disease presented at the screening visit. Examples of increased risk of muscle-invasive disease include but are not limited to: • Presence of lymphovascular invasion and / or micropapillary, sarcomatoid, plasmacytoid and / or neuroendocrine disease as shown in the histology of the biopsy sample • Subjects with CIS+T1 disease accompanied by the presence of hydronephrosis secondary to the primary tumour\n- Current or prior autoimmune disease\n- Immunocompromised, or immunodeficient, or undergoing any form of treatment known to cause immunosuppression\n- Symptomatic urinary tract infection or bacterial cystitis (once satisfactorily treated, subjects can enter the trial)\n- Clinically significant and unexplained elevated liver or renal function tests\n- Female subjects who are pregnant or lactating or refuse to commit to use contraception during the trial\n- Any other significant disease or other clinical findings which in the opinion of the investigator would prevent trial entry\n- History of malignancy of other organ system within past 5 years, except treated basal cell carcinoma or squamous cell carcinoma of the skin and ≤pT2 upper tract urothelial carcinoma at least 24 months after nephroureterectomy. Also subjects with genitourinary cancers other than urothelial cancer or prostate cancer, and subjects with renal mass ≤3 cm that are under active surveillance are excluded (see inclusion criterion 10)\n- Subjects who cannot hold instillation for 1 hour\n- Subjects who cannot tolerate intravesical dosing or intravesical surgical manipulation\n- Intravesical therapy within 8 weeks prior to beginning IMP with the exception of: • Cytotoxic agents (e.g., Mitomycin C, doxorubicin, epirubicin and gemcitabine) when administered as a single instillation immediately following a TURBT procedure, which is permitted within 70 days prior to beginning trial treatment • Previous intravesical BCG therapy, which can be given ≥5 weeks prior to the biopsy that is required for trial entry\n- Current systemic therapy for bladder cancer other than IMP used in randomisation arm\n- Current or prior investigational treatment for BCG-unresponsive NMIBC or any other investigational drug (drug used in a clinical trial, i.e. drug used in a Ferring sponsored non-interventional study does not apply) within 1 month prior to screening\n- Current or prior pelvic external beam radiotherapy within 2 years of screening\n- Prior treatment with nadofaragene firadenovec at any time\n- Prior systemic therapy for bladder cancer at any time\n- Prior intravesical chemotherapy for the treatment of BCG-unresponsive NMIBC (see exclusion criterion 19)\n- Use of other adenovirus vector-based drugs, e.g. COVID-19 vaccines, within 14 days before and after nadofaragene firadenovec instillation\n- Suspected hypersensitivity or immune-mediated reactions to any of the IMPs"}

Primary endpoints

• {"endpoint_text":"- Complete response ([CR] at any time from first treatment defined as absence of high-grade (HG) recurrence)","definition_or_measurement_approach":"Defined as complete response (CR) at any time from first treatment, specifically absence of high-grade (HG) recurrence"}

Methods

• Doctor-to-doctor (Dr to Dr) letters to referring clinicians (country-specific versions: e.g., K2_FR Dr to Dr Letter, K2_PL dr to pt letter, K2_DK dr to pt letter) to inform physicians about the study and refer patients
• Doctor-to-patient letters (country-specific) to inform eligible patients via their physicians
• Patient brochures and leaflets (country-specific localized brochures: PL, DK, CZ, FR, ES) distributed at sites and via clinicians
• Posters and flyers for display at clinical sites (country-specific poster with flyer materials)
• Email blasts and e-newsletter content targeting patients (PAG and study mailing lists) (documents: to pt email blast, enewsletter content)
• Patient video script / video content for awareness and information (Patient video script documents)
• Study-specific webpages and 'Find a site on website' materials to direct patients to recruiting sites (Patient information ABLE 22 study-specific website; Find a site on website)
• Patient advocacy group (PAG) materials and clinical study listings targeted to patient communities (PAG clinical study listing, PAG patient FAQ sheet)
• Patient information and FAQ sheets provided in local languages and English (country-specific K2 and L1 documents)
• Subject ID cards and study visit guides provided to enrolled participants

Poland

Earliest CTIS Part Ii Submission Date

12-06-2025

Latest Decision Or Authorization Date

26-01-2026

Processing Time Days

228

Number Of Sites

3

Number Of Participants

25

Denmark

Earliest CTIS Part Ii Submission Date

15-08-2025

Latest Decision Or Authorization Date

22-01-2026

Processing Time Days

160

Number Of Sites

1

Number Of Participants

8

Czechia

Earliest CTIS Part Ii Submission Date

08-08-2025

Latest Decision Or Authorization Date

22-01-2026

Processing Time Days

167

Number Of Sites

5

Number Of Participants

18

France

Earliest CTIS Part Ii Submission Date

12-06-2025

Latest Decision Or Authorization Date

21-01-2026

Processing Time Days

223

Number Of Sites

12

Number Of Participants

23

Spain

Earliest CTIS Part Ii Submission Date

08-08-2025

Latest Decision Or Authorization Date

23-01-2026

Processing Time Days

168

Number Of Sites

14

Number Of Participants

69

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

Operational support/clinical operations (sponsorDuties codes: [1,12,5]); contact email sm_clinopsams@syneoshealth.com

Third parties

• {"country":"Netherlands","full_name":"Syneos Health Netherlands B.V.","duties_or_roles":"sponsorDuties codes: [1,12,5]","organisation_type":"Pharmaceutical company"}