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A Phase III Study for Modification of Photodynamic Diagnosis of SPP-005 in Patients with Non-muscle Invasive Bladder Cancer (NMIBC) during Transurethral Resection of Bladder Tumor (TURBT)

A Phase III Study for Modification of Photodynamic Diagnosis of SPP-005

145

The average of age (mean +/- standard deviation) of the subjects in this study was 69.4 +/- 9.9 years old. The average of body weight (mean +/- standard deviation) was 64.22 +/- 12.70 kg. The proportions of male and female subjects were 81.3% and 18.8%, respectively, indicating a high proportion of males. The proportions of primary and recurrent cases were 63.2% and 36.8%, respectively, and the proportion of primary cases was high.

In this study, 161 subjects who consented were screened, and 149 (92.5%) were found eligible and randomized. Of the 149 subjects, 4 (2.5%) discontinued before receiving the investigational product, while 145 (90.1%) received the investigational product. No subjects discontinued the study after receiving the investigational product.

The incidence of adverse events (AEs) was 93.8% and blood pressure decreased, heamaturia, bladder spasm, dysuria, pollakiuria, constipation, nausea, hypotension, and hepatic function abnormal occurred in more than 10% of patients. All events except bladder spasm were known. No AEs leading to discontinuation of the study or death were observed. The incidence of serious AEs (SAEs) was 3.4%. The incidence of adverse drug reactions (ADRs) was 51.7% and hypotension and hepatic function abnormal, which events were known, occurred in more than 10% of patients. No serious ADRs were observed.

The primary endpoint was the sensitivity (95% confidence interval, CI) under blue light source (BL) that was 95.3% (92.4-97.3%) and its lower limit of the 95% CI was confirmed to exceed the threshold of the 95% CI that established for this study of 70%. This study achieved the primary endpoint. The sensitivity under BL was higher than that under the white light source (WL) of 61.1% (55.7-66.4%), a significant difference (p<0.001, McNemar test). The proportion of uroepithelial carcinoma in situ (CIS) detected only under BL was 68.7% (60.5-76.1%) and was also significantly higher than that only under WL, 0.7% (0.0-3.7%).

The phase III study was conducted to confirm sensitivity 4-8 hours prior to cystoscopy insertion in primary or recurrent NMIBC patients while TURBT. The primary endpoint was sensitivity under bule light that was 95.3% (92.4-97.3%) of which lower limit of 95% CI was confirmed above 70% threshold established for this study. This result met the primary endpoint and indicated non-inferiority to the previous. The incidences of AEs and ADRs were 93.8% and 51.7%, respectively, and no serious ADRs were observed.

Sept. 20, 2024

No

https://jrct.mhlw.go.jp/latest-detail/jRCT2061210055

Yamauchi Mitsugu

SBI Pharmaceuticals Co., Ltd.

1-6-1 Roppongi, Minato-ku, Tokyo

info_ala@sbigroup.co.jp

Yamauchi Mitsugu

SBI Pharmaceuticals Co., Ltd.

1-6-1 Roppongi, Minato-ku, Tokyo

+81-3-6229-0095

info_ala@sbigroup.co.jp

Complete

Jan. 06, 2022

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

diagnostic purpose

1) Patients who are eligible for TURBT
2) Patients who understand the informed consent document and can provide a written consent of their own free will
3) Patients who are between 20 and 85 years old (at the time of signing the informed consent document)
4) Patients with an ECOG Performance Status (ECOG PS) of 0 to 1 as determined at the time of enrollment
5) Patients whose clinical laboratory values meet the following criteria (laboratory tests within 28 days prior to IMP administration)
[Renal function]
Serum creatinine: Less than 1.5 times the upper limit of the institutional standard
[Hepatic function]
AST (GOT): Less than 1.5 times the upper limit of the institutional standard
ALT (GPT): Less than 1.5 times the upper limit of the institutional standard
Serum bilirubin: Less than 1.5 times the upper limit of the institutional standard
[Blood]
Platelet count:100,000/mm3 or more
6) Patients who are able to comply with the requirements of the study protocol, including the schedule of visit days
7) Patients suspected of having NMIBC, whether primary or recurrent, and in case of recurrence parents, at least 90 days have passed since the last day of the bladder cancer treatment.

1) Patients with a history of or complications from any of the following
- Myocardial infarction
- Congestive heart failure
- Angina pectoris requiring treatment
- Arrhythmia requiring treatment
2) Patients with serious complications (interstitial pneumonia, pulmonary fibrosis, poorly controlled hypertension, diabetes mellitus, etc.)
3) Patients with serious infectious diseases (including active tuberculosis)
4) Patients with active multiple cancers
5) Patients with systolic blood pressure of 100 mmHg or less, or diastolic blood pressure of 60 mmHg or less on the screening examination
6) Patients with a history of hypotension during previous TURBT
7) Female patients who are pregnant, lactating, or may be pregnant
8) Patients who do not intend to use contraception*
9) Patients with hypersensitivity or a history of hypersensitivity to porphyrin analogs.
10) Patients who have received any investigational medical product (including study drugs in post-marketing clinical studies) within 90 days prior to the start of screening examination
11) Patients who are scheduled to participate in clinical trials, etc. during the clinical trial period
12) Other patients who are judged to be inappropriate by the principal or sub investigators.
* Examples of contraception methods: condom, intrauterine device (IUD) and oral contraceptives (if a female participant use an oral contraceptive, a barrier method must be used concurrently).

Both

Non-muscle Invasive Bladder Cancer

Before TURBT, 20 mg/kg of aminolevulinic acid hydrochloride is dissolved in water and administered orally according to the assigned stratum dosing time.
-Stratum 1:Oral dose, 5 hours before TURBT(4 < t <= 6 hours)
-Stratum 2:Oral dose, 7 hours before TURBT(6 < t <= 8 hours)

Proportion of biopsy samples diagnosed as positive under BL out of the biopsy samples confirmed pathologically positive those collected during TURBT when SPP-005 administrates 4-8 hours before inserting the cystoscope (sensitivity).

+81-88-880-2627

Dec. 14, 2021

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