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A Single-blind, Randomized, Controlled, Parallel-group, Comparative Study Evaluating the Safety and Effectiveness of VER-01 as an Adjunct to Sealing Sutured Cranial Dural Repair

VER-01 Sealing Sutured Cranial Dural Repair Study

131

No major bias was observed in the distribution of each item of subject demographic and baseline characteristics between the treatment groups. Overall, 56.5% (74/131 subjects) were female and the mean age (SD) was 53.2 (14.4) years. All subjects were Japanese except 1 Asian subject (non-Japanese). There was no major bias in the distribution of surgical information between the treatment groups. Overall, the most common target disease was cancer (27.5%, 36/131 subjects), followed by cerebral aneurysm (9.9%, 13/131 subjects). The surgical procedure was craniotomy in all subjects. The surgical site was supratentorial in 60.3% (79/131 subjects), followed by posterior fossa in 39.7% (52/131 subjects).

Of the 144 patients who consented to participate in the study, 131 patients were enrolled, excluding 13 patients who were screen failures. All enrolled subjects were randomized (66 subjects in VER-01 group, 65 subjects in Beriplast P group), and all received investigational product. A total of 126 subjects (62 subjects, 64 subjects) completed the study. 131 randomized subjects (66 subjects in VER-01 group, 65 subjects in Beriplast P group) were included in the ITT. Since all subjects in the ITT received investigational product of the randomized group, the ITT, mITT, and SAF were the same. A total of 128 subjects (64 patients in VER-01 group, 64 patients in Beriplast P group) were included in the PPS, excluding 3 subjects (n = 2, n = 1) with major protocol violations/deviations from the mITT.

The incidence of adverse events in the SAF was 63.6% (42/66 subjects) in the VER-01 group and 52.3% (34/65 subjects) in the Beriplast P group. Of these, the incidence of serious AEs was 13.6% (9/66 subjects) in VER-01 group and 3.1% (2/65 subjects) in Beriplast P group, respectively, and the incidence of severe AEs was 10.6% (7/66 subjects) in VER-01 group and 3.1% (2/65 subjects) in Beriplast P group, respectively. AEs reported in >= 5% of subjects in the VER-01 group were constipation (16.7% [11/66 subjects]), nausea (15.2% [10/66 subjects]), procedural pain (13.6% [9/66 subjects]), insomnia (12.1% [8/66 subjects]), cerebrospinal fluid leakage (9.1% [6/66 subjects]), cerebral infarction (7.6% [5/66 subjects]), hypoaesthesia, vomiting, and malaise (6.1% [4/66 subjects] each). In the Beriplast P group, the most frequently reported AEs (>= 5% of subjects) were procedural pain (16.9% [11/65 subjects]), constipation (13.8% [9/65 subjects]), nausea (12.3% [8/65 subjects]), hyperglycemia and cerebrospinal fluid leakage (9.2% [6/65 subjects] each), and malaise and pyrexia (7.7% [5/65 subjects] each).Of these, adverse events with >= 5% higher incidence in the VER-01 group than in the Beriplast P group were insomnia and cerebral infarction. In all of these cases, a causal relationship with the investigational drug was denied (not related). The incidence of AEs related to investigational product was 1.5% (1/66) in VER-01 group and 6.2% (4/65) in Beriplast P group, respectively, all of which were CSF leakage. Of these, no SAEs or severe AEs were reported in either treatment group. No AEs related to the concomitant medical device were reported in either treatment group. There were no adverse drug reactions with an incidence of >= 5% in the VER-01 group. The adverse reaction with incidence >= 5% in the Beriplast P group was cerebrospinal fluid leakage (6.2%, 4/65 subjects). The incidence of procedure-related adverse events was 6.1% (4/66 subjects) in VER-01 group and 3.1% (2/65 subjects) in Beriplast P group, respectively, and of these events, the incidence of serious adverse events and severe adverse events was 1.5% (1/66 subjects) in VER-01 group and 1.5% (1/65 subjects) in Beriplast P group, respectively.

<Primary Endpoint>(Analysis set: mITT) - Incidence of cerebrospinal fluid leakage or pseudomeningocele from postoperative day to postoperative day 7 (+/- 2 days) CT scan within 5 mm slice thickness was necessary after surgery within 7 days (+/-2 days) following surgery. CT imaging was not necessary when CSF leak was visually apparent. The subjects with "(event) onset" included the subjects who received additional treatment other than investigational product before head closure, the subjects who experienced "dural closure failure" due to liquorrhea after the second application of investigational product, and the subjects who were not evaluated by the Valsalva maneuver for the second time (or the first time if the second application was not necessary; however, if cerebrospinal fluid leakage was observed spontaneously, Valsalva maneuver was not necessary). For liquorrhea or pseudomeningocele, events with the onset date of the adverse event included in the period from Day 1 to Day 10 were to be included in the assessment of the primary endpoint. Any occurrence of cerebrospinal fluid leak or pseudomeningocele was to be included regardless of causal relationship to investigational or comparator product. 90.9% (60/66 subjects) (95% CI: 81.3~96.6) in the VER-01 group and 90.8% (59/65 subjects) (95% CI: 81.0~96.5) in the Beriplast P group Any occurrence of cerebrospinal fluid leak or pseudomeningocele was included regardless of causal relationship to investigational or comparator product. The difference in the success rate for dural closure between the VER-01 group and the Beriplast P group was 0.1% (95% CI: -11.1~11.4). <Secondary Endpoint>(Analysis set: mITT) - Success rate of intraoperative cranial repair A subject was considered a success due to absence of intra-operative CSF leak in the surgical area after second application (or first application if the second application was unnecessary) following the final Valsalva maneuver performed to a pressure between 20-25 cm H2O for 5-10 seconds. For the success rate of dural closure during surgery, subjects who received additional treatment other than investigational product before head closure were also considered as "failed dural closure." 98.5% (65/66 subjects) (95%CI: 91.8~100.0) in the VER-01 group, 98.5% (64/65 subjects) (95%CI: 91.7~100.0) in the Beriplast P group - Incidence of cerebrospinal fluid leakage or pseudomeningocele from the postoperative period to 30 days (+ 15 days) after surgery 16.7% (11/66 subjects) (95%CI: 8.6~27.9) in the VER-01 group, 12.3% (8/65 subjects) (95%CI: 5.5~22.8) in the Beriplast P group - Incidence of meningitis from the postoperative period to 30 days (+ 15 days) after surgery 7.6% (5/66 subjects) (95%CI: 2.5~16.8) in the VER-01 group, and 3.1% (2/65 subjects) (95%CI: 0.4~10.7) in the Beriplast P group For postoperative liquorrhea, pseudomeningocele, and meningitis, the subjects who experienced (event) will include those who received additional treatment other than investigational product before cephalic closure, those who experienced liquorrhea after the second application of investigational product and became "dural closure failure, " and those who were not evaluated by the second Valsalva maneuver (However, if cerebrospinal fluid leakage is observed spontaneously, Valsalva maneuver was not necessary). Adverse events whose onset date falls between Day 1 and Day 46 were also included. Neither pseudomeningocele nor meningitis occurred as an adverse event. These "event" subjects included two cases (one in the VER-01 group and one in the Beriplast P group) in which the Valsalva maneuver was not confirmed at the second evaluation during surgery (or at the first evaluation if the second application was not necessary), and five discontinued cases (four in the VER-01 group and one in the Beriplast P group) with missing data at 30 days (+15 days) after surgery.

These results demonstrated the non-inferiority of VER-01 to Beriplast P as an adjunct to tissue closure following dural sutures in patients undergoing elective posterior fossa or supratentorial craniotomy/decompressive craniectomy.

Mar. 31, 2026

No

https://jrct.mhlw.go.jp/latest-detail/jRCT2031230364

Deura Imari

Johnson & Johnson K.K.

3-5-2, Nishi-Kanda, Chiyoda-ku, Tokyo, 101-0065, Japan

JJ_clinical@its.jnj.com

Dedicated contact

Johnson&Johnson K.K.

3-5-2, Nishi-Kanda, Chiyoda-ku, Tokyo, 101-0065, Japan

+81-3-4411-7200

JJ_clinical@its.jnj.com

Complete

Oct. 01, 2023

Interventional

randomized controlled trial

single blind

active control

parallel assignment

treatment purpose

Pre-operative
1.Subjects undergoing an elective craniotomy or decompressive craniectomy surgery in supratentorial or posterior fossa
2.At least 18 years of age at the time of informed consent.
3.Willingness to comply with the protocol.
4.Willingness to give consent before all study-related activities.

Intra-operative
1.Surgical wound classification Class I. Superficial penetration of mastoid air cells during partial mastoidectomy is permitted.
2.The cuff of native dura along the craniotomy edge on each side is adequate, based on judgement of principal investigator or sub-investigator, to facilitate suturing and to allow for sufficient surface area for adherence of the sealant
3.Presence of intra-operative spontaneous cerebrospinal fluid (CSF) leakage following sutured dural closure or after Valsalva maneuver. If a spontaneous leak is apparent immediately after dural closure, no Valsalva maneuver will be performed.

Pre-operative
1.Subjects with a cranial dural lesion from a recent surgery that still has the potential for CSF leakage.
2.Chemotherapy scheduled within 30 days prior to enrollment or scheduled within 7 days following surgery.
3.Radiation therapy to the head scheduled within 30 days prior to enrollment or scheduled within 7 days following surgery.
4.Corticosteroids on a chronic basis (more than 6 weeks) unless treatment is discontinued 4 weeks prior to planned surgery
5.Subjects who have intolerance to any of the components of the investigational or comparator products (including bovine-derived ingredients).
6.Subjects who are not willing to use blood products.
7.Subjects with any other pre-operative finding identified by the surgeon that in their opinion, may affect the primary or secondary endpoints such as severely altered renal or hepatic function, compromised immune system, autoimmune disease or uncontrolled/poorly controlled diabetes with the risk of wound healing complication.
8.Subjects who have hydrocephalus (unless hydrocephalus caused by posterior fossa pathology or incompletely open cerebrospinal fluid pathways is treated in this study)
9.Subjects with traumatic injuries to the head with damage to the dura and/or with an existing shunt or drain for decompression.
10.Subjects of childbearing potential with a positive pregnancy test or those who intend to become pregnant during the clinical study period.
11.Subjects who are breastfeeding.
12.Subjects who have participated in or will participate in another clinical trial of another a test drug/device within 30 days of a surgery of the clinical trial.
13.Subjects judged to be inappropriate by the principal investigator or sub-investigator.

Intra-operative
1.Unintentional dural tears during craniotomy/ decompressive craniectomy that cannot be suture repaired.
2.Subject has a gap between durotomy edges of greater than 2 mm after primary dural closure.
3.Use of implants made of synthetic materials that cannot be sutured to dura, shunts, ventricular and subdural drains.
4.Intersecting durotomy scars in the surgical path from a previous operation that cannot be completely removed by the planned dural resection.
5.Placement of Gliadel Wafers
6.Two or more separate dural defects.
7.Subjects who have serious complication in surgeries requiring emergency resuscitation or changing of planned surgeries.
8.Subjects judged to be inappropriate by the principal investigator or sub-investigator.

Both

Elective craniotomy or decompressive craniectomy surgery in supratentorial or posterior fossa

Subjects, who are undergoing sutured dural repair following procedures in the supratentorial region or posterior fossa, will be evaluated for intra-operative cerebrospinal fluid (CSF) leakage with a baseline Valsalva maneuver performed to a pressure between 20-25 cm H2O for 5-10 seconds. If a spontaneous leak is apparent immediately after dural closure, no Valsalva maneuver will be performed. Subjects who have exudative CSF leakage are enrolled will be randomized to VER-01 or Beriplast P in a 1:1 allocation ratio.

Incidence rate of post-operative CSF leak or pseudomeningocele in the surgical area within 7 days (plus or minus 2 days) following surgery.
Computerized tomography (CT) scan within 5 mm slice thickness is necessary after surgery within 7 days (plus or minus 2 days) following surgery. The imaging is not necessary when CSF leak is visually apparent.

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