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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 : Recruiting
First Posted : November 15, 2019
Last Update Posted : May 5, 2020
Sponsor:
Information provided by (Responsible Party):
Agios Pharmaceuticals, Inc.

Tracking Information
First Submitted Date  ICMJE November 11, 2019
First Posted Date  ICMJE November 15, 2019
Last Update Posted Date May 5, 2020
Actual Study Start Date  ICMJE January 5, 2020
Estimated Primary Completion Date October 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 14, 2019)
Progression-Free Survival (PFS) [ Time Frame: Up to approximately 30 months ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 14, 2019)
  • Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to approximately 30 months ]
  • Tumor Growth Rate as Assessed by Volume [ Time Frame: Up to approximately 30 months ]
  • Time to Next Intervention [ Time Frame: Up to approximately 5 years ]
  • Objective Response Rate [ Time Frame: Up to approximately 30 months ]
  • Time to Response [ Time Frame: Up to approximately 30 months ]
  • Duration of Response [ Time Frame: Up to approximately 30 months ]
  • Overall Survival [ Time Frame: Up to approximately 5 years ]
  • 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.
  • Progression-Free Survival (PFS) as Assessed by the Investigator [ Time Frame: Up to approximately 30 months ]
  • 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 ]
  • 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 ]
  • 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 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of AG-881 in Participants With Residual or Recurrent Grade 2 Glioma With an IDH1 or IDH2 Mutation (INDIGO)
Official Title  ICMJE 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
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 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 366 participants are planned to be randomized 1:1 to receive orally administered AG-881 40 mg QD or placebo.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE 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
Condition  ICMJE
  • Grade 2 Glioma
  • Residual Glioma
  • Recurrent Glioma
Intervention  ICMJE
  • Drug: AG-881
    AG-881 oral film-coated tablets
  • Drug: Matching Placebo
    Matching Placebo oral tablets
Study Arms  ICMJE
  • Experimental: AG-881
    AG-881 40 mg, continuous daily dosing.
    Intervention: Drug: AG-881
  • Placebo Comparator: Matching Placebo
    Matching placebo 40 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.
    Intervention: Drug: Matching Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 14, 2019)
366
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 2028
Estimated Primary Completion Date October 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 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, 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).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Medical Affairs Agios Pharmaceuticals, Inc 833-228-8474 medinfo@agios.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04164901
Other Study ID Numbers  ICMJE AG881-C-004
2019‐002481‐13 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Agios Pharmaceuticals, Inc.
Study Sponsor  ICMJE Agios Pharmaceuticals, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Agios Pharmaceuticals, Inc.
Verification Date May 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP