Neurofibromatosis Type 2
Conditions
Keywords
Neurofibromatosis Type 2; Neurofibromatosis Type II
Brief summary
This is a two-staged, Phase 2/3, randomized, multi-center study to investigate the efficacy and safety of REC-2282 in participants with progressive NF2 mutated meningiomas.
Detailed description
Cohort A (Phase 2) will provide early data on efficacy and safety of REC-2282 in participants with progressive NF2 mutated meningiomas, and provide guidance for the dose in the confirmatory part of the study (Cohort B, Phase 3). The purpose of Cohort B of the study is to assess the efficacy and safety of REC-2282 compared with placebo in participants with progressive NF2 mutated meningiomas. In both cohorts, there will be a screening period of up to 8 weeks, a treatment period, a 4-week safety follow-up period after the end of treatment, and a 6-month post-study follow-up. The first 8 participants enrolled in Cohort A will complete a food effect run-in sub study. At the end of the study period, participants may be offered participation in an open-label extension (OLE) period. In Cohort A, adult participants will be randomized to one of two dose levels of REC-2282. In Cohort B, participants will be randomized to REC-2282 treatment (dose to be determined from Cohort A) arm or placebo arm in a ratio of 2:1.
Interventions
DRUGREC-2282
Participants will receive REC-2282 3 times per week orally for 3 weeks followed by 1 week off for a 4-week cycle.
DRUGPlacebo
Participants will receive placebo orally 3 times per week for 3 weeks followed by 1 week off for a 4-week cycle.
Sponsors
Recursion Pharmaceuticals Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Masking applies to Cohort B only.
Intervention model description
A Two-staged, Phase 2/3, Randomized, Multicenter Efficacy and Safety Study.
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. ≥12 years of age and weighing at least 40 kg 2. Progressive meningioma that is amenable to volumetric analysis 3. Has either 1) sporadic meningioma with confirmed NF2 mutation; or, 2) confirmed diagnosis of NF2 disease (revised Manchester criteria); or, 3) at least one NF2-related tumor (with pathogenic germline or proven mosaic NF2 variant) 4. Adequate bone marrow function 5. Has provided written informed consent/assent to participate in the study
Exclusion criteria
1. Progressive disease associated with significant or disabling clinical symptoms likely to require surgery or radiation therapy within the next 3 months. 2. Received prior surgery, radiosurgery, or laser interstitial thermal therapy in the target tumor, or immediately adjacent to the target tumor within 12 months prior to screening. 3. Received an anti- tumor agent for meningioma within 3 months, or 5 half-lives (whichever is longer), prior to screening. 4. History of an active malignancy within the previous 3 years except for localized cancers that are considered cured, and, in the opinion of the investigator, present a low risk of recurrence. 5. Received another investigational drug within 30 days prior to screening 6. Pregnant, lactating, or is planning to attempt to become pregnant or impregnate someone during this study or within 90 days after the last dosing cycle.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cohort A: Number of Participants with Progression-free survival (PFS) at 6 Months | 6 months | In Cohort A, PFS is defined as the number of participants who are alive and progression-free at 6 months with progression defined as having an increase of 20% or more in the target tumor identified. |
| Cohort B: Number of Participants with PFS up to 3 years | Up to 3 years | In Cohort B, PFS is defined as the time from the date of randomization until disease progression or death from any cause, whichever occurs first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cohort A: Change from Baseline in Target Tumor Volume at 6 Months | 6 months | — |
| Cohort A: Number of Participants with PFS at 12 and 24 Months | 12 and 24 Months | In Cohort A, PFS is defined as the number of participants who are alive and progression-free at 12 and 24 months with progression defined as having an increase of 20% or more in the target tumor identified. |
| Cohorts A and B: Objective Response Rate (ORR) | Up to 3 years | — |
| Cohorts A and B: Disease Control Rate (DCR) | Up to 3 years | — |
| Cohorts A and B: Time to Response (TTR) | Up to 3 years | — |
| Cohorts A and B: Duration of Response (DOR) | Up to 3 years | — |
| Cohorts A and B: Time to Surgery/radiation for Target Tumors | Up to 3 years | — |
| Cohorts A and B: Maximum Observed Plasma Concentration (Cmax) of REC-2282 | Up to 3 years | — |
| Cohorts A and B: Time to Maximum Plasma Concentration (Tmax) of REC-2282 | Up to 3 years | — |
| Cohorts A and B: Area under the curve from 0 to 24hr (AUC) of REC-2282 | Predose to 24 hours postdose | — |
Countries
United Kingdom, United States
Outcome results
None listed