Clinical Trials /

Study of AG-881 in Participants With Residual or Recurrent Grade 2 Glioma With an IDH1 or IDH2 Mutation (INDIGO)

NCT04164901

Description:

Study AG881-C-004 is a phase 3, multicenter, randomized, double-blind, placebo-controlled study comparing the efficacy of AG-881 to placebo in participants will 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 366 participants are planned to be randomized 1:1 to receive orally administered AG-881 50 mg QD or placebo.

Related Conditions:
  • Astrocytoma
  • Oligodendroglioma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Study of 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

DrugSynonymsArms
AG-881AG-881
Matching PlaceboMatching Placebo

Purpose

Study AG881-C-004 is a phase 3, multicenter, randomized, double-blind, placebo-controlled study comparing the efficacy of AG-881 to placebo in participants will 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 366 participants are planned to be randomized 1:1 to receive orally administered AG-881 50 mg QD or placebo.

Trial Arms

NameTypeDescriptionInterventions
AG-881ExperimentalAG-881 50 mg, continuous daily dosing.
  • AG-881
Matching PlaceboPlacebo ComparatorMatching placebo 50 mg, continuous daily dosing. Participants who experience radiographic disease progression and who were receiving placebo will have the option to cross-over to AG-881, provided certain criteria are met.
  • Matching Placebo

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 and not more
             than 5 years before the date of randomization, and no other prior anticancer therapy,
             including chemotherapy and radiotherapy.

          -  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 blinded
             independent review committee (BIRC)

          -  Have Karnofsky performance status (KPS) ≥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, etc.

          -  Have high-risk features as assessed 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: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
Time Frame:Up to approximately 30 months
Safety Issue:
Description:
Measure:Time to Next Intervention
Time Frame:Up to approximately 5 years
Safety Issue:
Description:
Measure:Objective Response Rate
Time Frame:Up to approximately 30 months
Safety Issue:
Description:
Measure:Time to Response
Time Frame:Up to approximately 30 months
Safety Issue:
Description:
Measure:Duration of Response
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:Maximum Observed Serum Concentration (Cmax) of AG-881
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:Area Under Concentration Time Curve from Time 0 to Tau (AUC0-tau) of AG-881
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:Time to Reach Maximum Serum Concentration (Tmax) of AG-881
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

  • vorasidenib

Last Updated

December 13, 2019