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

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ClinicalTrials.gov Identifier: NCT04164901
Recruitment Status : Not yet recruiting
First Posted : November 15, 2019
Last Update Posted : November 22, 2019
Sponsor:
Information provided by (Responsible Party):
Agios Pharmaceuticals, Inc.

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Grade 2 Glioma Residual Glioma Recurrent Glioma Drug: AG-881 Drug: Matching Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 366 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Participants randomized in a 1:1 allocation (AG-881 vs Placebo)
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Estimated Study Start Date : December 2019
Estimated Primary Completion Date : October 2024
Estimated Study Completion Date : April 2028

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: AG-881
AG-881 50 mg, continuous daily dosing.
Drug: AG-881
AG-881 oral tablets

Placebo Comparator: Matching Placebo
Matching 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.
Drug: Matching Placebo
Matching Placebo oral tablets




Primary Outcome Measures :
  1. Progression-Free Survival (PFS) [ Time Frame: Up to approximately 30 months ]

Secondary Outcome Measures :
  1. Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to approximately 30 months ]
  2. Tumor Growth Rate as Assessed by Volume [ Time Frame: Up to approximately 30 months ]
  3. Time to Next Intervention [ Time Frame: Up to approximately 5 years ]
  4. Objective Response Rate [ Time Frame: Up to approximately 30 months ]
  5. Time to Response [ Time Frame: Up to approximately 30 months ]
  6. Duration of Response [ Time Frame: Up to approximately 30 months ]
  7. Overall Survival [ Time Frame: Up to approximately 5 years ]
  8. Health-Related Quality of Life as Measured by Functional Assessment of Cancer Therapy-Brain Questionnaire (FACT-Br) [ Time Frame: Up to approximately 30 months ]
    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.

  9. Progression-Free Survival (PFS) as Assessed by the Investigator [ Time Frame: Up to approximately 30 months ]
  10. 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 ]
  11. 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 ]
  12. 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 ]


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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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).

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Responsible Party: Agios Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT04164901     History of Changes
Other Study ID Numbers: AG881-C-004
2019‐002481‐13 ( EudraCT Number )
First Posted: November 15, 2019    Key Record Dates
Last Update Posted: November 22, 2019
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Agios Pharmaceuticals, Inc.:
vorasidenib
Additional relevant MeSH terms:
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Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue