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Study of Vorasidenib (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 : Recruiting
First Posted : November 15, 2019
Last Update Posted : June 25, 2021
Sponsor:
Information provided by (Responsible Party):
Agios Pharmaceuticals, Inc.

Study Description
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Brief Summary:
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.

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

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 340 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Participants randomized in a 1:1 allocation (vorasidenib 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
Actual Study Start Date : January 5, 2020
Estimated Primary Completion Date : October 2024
Estimated Study Completion Date : August 2027

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Arms and Interventions
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Arm Intervention/treatment
Experimental: Vorasidenib
Vorasidenib 40 mg, continuous daily dosing.
 Drug: Vorasidenib
Vorasidenib oral film-coated tablets
Other Name: AG-881
Placebo Comparator: Matching Placebo
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.
 Drug: Matching Placebo
Matching Placebo oral tablets


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

Secondary Outcome Measures :
  1. Time to Next Intervention [ Time Frame: Up to approximately 5 years ]
  2. Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to approximately 30 months ]
  3. Tumor Growth Rate as Assessed by Volume per the Blinded Independent Review Committee (BIRC) [ Time Frame: Up to approximately 30 months ]
  4. Objective Response as Assessed per the BIRC and Investigator [ Time Frame: Up to approximately 30 months ]
  5. Complete Response (CR) + Partial Response (PR) with Response Assessed per the BIRC and Investigator [ Time Frame: Up to approximately 30 months ]
  6. Time to Response with Response Assessed per the BIRC and Investigator [ Time Frame: Up to approximately 30 months ]
  7. Time to CR + PR with Response Assessed per the BIRC and Investigator [ Time Frame: Up to approximately 30 months ]
  8. Duration of Response with Response Assessed per the BIRC and Investigator [ Time Frame: Up to approximately 30 months ]
  9. Duration of CR + PR with Response Assessed per the BIRC and Investigator [ Time Frame: Up to approximately 30 months ]
  10. Overall Survival [ Time Frame: Up to approximately 5 years ]
  11. 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.

  12. Progression-Free Survival (PFS) as Assessed by the Investigator [ Time Frame: Up to approximately 30 months ]
  13. 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 ]
  14. 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 ]

Eligibility Criteria
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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 (-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).
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04164901


Contacts
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Contact: Medical Affairs Agios Pharmaceuticals, Inc 833-228-8474 medinfo@agios.com

Locations
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Sponsors and Collaborators
Agios Pharmaceuticals, Inc.
More Information
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Responsible Party: Agios Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT04164901    
Other Study ID Numbers: AG881-C-004
2019-002481-13 ( EudraCT Number )
First Posted: November 15, 2019    Key Record Dates
Last Update Posted: June 25, 2021
Last Verified: June 2021
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.:
AG-881
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