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

• ClinicalTrials.gov Identifier: NCT04164901
• Recruitment Status: Recruiting
• First Posted: November 15, 2019
• Last Update Posted: December 24, 2020
• Sponsor: Agios Pharmaceuticals, Inc.
• Information provided by (Responsible Party): Agios Pharmaceuticals, Inc.

Tracking Information

• First Submitted Date: November 11, 2019
• First Posted Date: November 15, 2019
• Last Update Posted Date: December 24, 2020
• Actual Study Start Date: January 5, 2020
• Estimated Primary Completion Date: October 2024 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: November 14, 2019): Progression-Free Survival (PFS) [ Time Frame: Up to approximately 30 months ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (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: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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: Interventional
• Study Phase: Phase 3

Study Design

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

• Grade 2 Glioma
• Residual Glioma
• Recurrent Glioma

Intervention

• Drug: AG-881
  AG-881 oral film-coated tablets
• Drug: Matching Placebo
  Matching Placebo oral tablets

Study Arms

• 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

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 14, 2019): 366
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: April 2028
• Estimated Primary Completion Date: October 2024 (Final data collection date for primary outcome measure)

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 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

• Sexes Eligible for Study: All

• Ages: 12 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

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

• Listed Location Countries: Canada, France, Germany, Israel, Italy, Netherlands, Spain, United States

Administrative Information

• NCT Number: NCT04164901
• Other Study ID Numbers: 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

• Plan to Share IPD: No

• Responsible Party: Agios Pharmaceuticals, Inc.
• Study Sponsor: Agios Pharmaceuticals, Inc.
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Agios Pharmaceuticals, Inc.
• Verification Date: December 2020