Description:
Study AG881-C-004 is a phase 3, multicenter, randomized, double-blind, placebo-controlled
study comparing the efficacy of vorasidenib to placebo in participants with residual or
recurrent Grade 2 glioma with an IDH1 or IDH2 mutation who have undergone surgery as their
only treatment. Participants will be required to have central confirmation of IDH mutation
status prior to randomization. Approximately 340 participants are planned to be randomized
1:1 to receive orally administered vorasidenib 40 mg QD or placebo.
Title
- Brief Title: Study of Vorasidenib (AG-881) in Participants With Residual or Recurrent Grade 2 Glioma With an IDH1 or IDH2 Mutation (INDIGO)
- Official Title: A Phase 3, Multicenter, Randomized, Double-blind, Placebo-Controlled Study of AG-881 in Subjects With Residual or Recurrent Grade 2 Glioma With an IDH1 or IDH2 Mutation
Clinical Trial IDs
- ORG STUDY ID:
AG881-C-004
- SECONDARY ID:
2019-002481-13
- NCT ID:
NCT04164901
Conditions
- Grade 2 Glioma
- Residual Glioma
- Recurrent Glioma
Interventions
Drug | Synonyms | Arms |
---|
Vorasidenib | AG-881 | Vorasidenib |
Matching Placebo | | Matching Placebo |
Purpose
Study AG881-C-004 is a phase 3, multicenter, randomized, double-blind, placebo-controlled
study comparing the efficacy of vorasidenib to placebo in participants with residual or
recurrent Grade 2 glioma with an IDH1 or IDH2 mutation who have undergone surgery as their
only treatment. Participants will be required to have central confirmation of IDH mutation
status prior to randomization. Approximately 340 participants are planned to be randomized
1:1 to receive orally administered vorasidenib 40 mg QD or placebo.
Trial Arms
Name | Type | Description | Interventions |
---|
Vorasidenib | Experimental | Vorasidenib 40 mg, continuous daily dosing. | |
Matching Placebo | Placebo Comparator | Matching placebo 40 mg, continuous daily dosing. Participants who experience centrally-confirmed radiographic disease progression and who were receiving placebo will have the option to cross-over to vorasidenib, provided certain criteria are met. | |
Eligibility Criteria
Key Inclusion Criteria:
- Be at least 12 years of age and weigh at least 40 kg.
- Have Grade 2 oligodendroglioma or astrocytoma per WHO 2016 criteria.
- Have had at least 1 prior surgery for glioma (biopsy, sub-total resection, gross-total
resection), with the most recent surgery having occurred at least 1 year (-1 month)
and not more than 5 years (+3 months) before the date of randomization, and no other
prior anticancer therapy, including chemotherapy and radiotherapy and not be in need
of immediate chemotherapy or radiotherapy in the opinion of the Investigator.
- Have confirmed IDH1 (IDH1 R132H/C/G/S/L mutation variants tested) or IDH2 (IDH2
R172K/M/W/S/G mutation variants tested) gene mutation status disease by central
laboratory testing during the Prescreening period and available 1p19q status by local
testing (eg, fluorescence in situ hybridization [FISH], comparative genomic
hybridization [CGH] array, sequencing) using an accredited laboratory.
- Have MRI-evaluable, measurable, non-enhancing disease, as confirmed by the BIRC.
- Have a Karnofsky Performance Scale (KPS) score (for participants ≥16 years of age) or
Lansky Play Performance Scale (LPPS) score (for participants <16 years of age) of
≥80%.
Key Exclusion Criteria:
- Have had any prior anticancer therapy other than surgery (biopsy, sub-total resection,
gross-total resection) for treatment of glioma including systemic chemotherapy,
radiotherapy, vaccines, small-molecules, IDH inhibitors, investigational agents, laser
ablation, etc.
- Have features assessed as high-risk by the Investigator, including brainstem
involvement either as primary location or by tumor extension, clinically relevant
functional or neurocognitive deficits due to the tumor in the opinion of the
Investigator (deficits resulting from surgery are allowed), or uncontrolled seizures
(defined as persistent seizures interfering with activities of daily life AND failed 3
lines of antiepileptic drug regimens including at least 1 combination regimen).
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 12 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Progression-Free Survival (PFS) |
Time Frame: | Up to approximately 30 months |
Safety Issue: | |
Description: | |
Secondary Outcome Measures
Measure: | Time to Next Intervention |
Time Frame: | Up to approximately 5 years |
Safety Issue: | |
Description: | |
Measure: | Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) |
Time Frame: | Up to approximately 30 months |
Safety Issue: | |
Description: | |
Measure: | Tumor Growth Rate as Assessed by Volume per the Blinded Independent Review Committee (BIRC) |
Time Frame: | Up to approximately 30 months |
Safety Issue: | |
Description: | |
Measure: | Objective Response as Assessed per the BIRC and Investigator |
Time Frame: | Up to approximately 30 months |
Safety Issue: | |
Description: | |
Measure: | Complete Response (CR) + Partial Response (PR) with Response Assessed per the BIRC and Investigator |
Time Frame: | Up to approximately 30 months |
Safety Issue: | |
Description: | |
Measure: | Time to Response with Response Assessed per the BIRC and Investigator |
Time Frame: | Up to approximately 30 months |
Safety Issue: | |
Description: | |
Measure: | Time to CR + PR with Response Assessed per the BIRC and Investigator |
Time Frame: | Up to approximately 30 months |
Safety Issue: | |
Description: | |
Measure: | Duration of Response with Response Assessed per the BIRC and Investigator |
Time Frame: | Up to approximately 30 months |
Safety Issue: | |
Description: | |
Measure: | Duration of CR + PR with Response Assessed per the BIRC and Investigator |
Time Frame: | Up to approximately 30 months |
Safety Issue: | |
Description: | |
Measure: | Overall Survival |
Time Frame: | Up to approximately 5 years |
Safety Issue: | |
Description: | |
Measure: | Health-Related Quality of Life as Measured by Functional Assessment of Cancer Therapy-Brain Questionnaire (FACT-Br) |
Time Frame: | Up to approximately 30 months |
Safety Issue: | |
Description: | The FACT-Br is a participant-reported measure designed to assess the quality of life for participants with brain tumors. The FACT-Br is a measure comprising the following subscales: Physical Well-Being, Functional Well-Being, Emotional Well-Being, and Social Well-Being subscales from the FACT-G, with the addition of a brain tumor- specific subscale. |
Measure: | Progression-Free Survival (PFS) as Assessed by the Investigator |
Time Frame: | Up to approximately 30 months |
Safety Issue: | |
Description: | |
Measure: | Pharmacokinetics: Plasma Concentrations of Vorasidenib Collected at Specified Time Points |
Time Frame: | Days 1 and 15 of Cycle 1(predose and multiple timepoints up to 4 hours postdose), Day 1 of Cycle 2(predose and multiple time points up to 4 hours postdose), Predose on Day 1 of every cycle thereafter(each cycle is 28 days), and within 7 days of last dose |
Safety Issue: | |
Description: | |
Measure: | Pharmacokinetics: Plasma Concentrations of Metabolite, AGI-69460, Collected at Specified Time Points |
Time Frame: | Days 1 and 15 of Cycle 1(predose and multiple timepoints up to 4 hours postdose), Day 1 of Cycle 2(predose and multiple time points up to 4 hours postdose), Predose on Day 1 of every cycle thereafter(each cycle is 28 days), and within 7 days of last dose |
Safety Issue: | |
Description: | |
Details
Phase: | Phase 3 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Agios Pharmaceuticals, Inc. |
Trial Keywords
Last Updated
June 25, 2021