Study of AG-881 in Subjects With Residual or Recurrent Grade 2 Glioma With an IDH1 or IDH2 Mutation

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Institut De Recherches Internationales Servier IRIS

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

5 Aug 2020 → ongoing

Decision date (initial)

2024-07-22

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

LLC

External identifiers

EU CT number

2024-512961-15-00

EudraCT number

2019-002481-13

ClinicalTrials.gov

NCT04164901

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Efficacy, Therapy, Pharmacodynamic, Safety

The primary objective of the study is to demonstrate the efficacy of vorasidenib based on radiographic PFS per BIRC compared with placebo in subjects with residual or recurrent Grade 2 oligodendroglioma and astrocytoma with an IDH1 or IDH2 mutation who have undergone surgery as their only treatment.

Secondary objectives 1

1. • To demonstrate the efficacy of vorasidenib based on time to next intervention (TTNI) compared with placebo. To evaluate the safety and tolerability of vorasidenib. • To evaluate vorasidenib and placebo with respect to tumor growth rate (TGR) as assessed by volume per the BIRC. • To evaluate the efficacy of vorasidenib and placebo based on objective response, CR+PR, time to response (TTR), time to CR+PR, duration of response (DoR), and duration of CR+PR, with response assessed per the BIRC and the Investigator. • To evaluate vorasidenib and placebo with respect to OS. • To evaluate vorasidenib and placebo with respect to health-related quality of life (HRQoL) as assessed by the Functional Assessment of Cancer Therapy – Brain (FACT-Br) questionnaire. • To evaluate vorasidenib and placebo with respect to PFS per the Investigator assessment. • To evaluate the PK of vorasidenib and its circulating metabolite AGI-69460 in plasma

Conditions and MedDRA coding

Residual or Recurrent Grade 2 Glioma With an IDH1 or IDH2 Mutation

Study design 4 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

IPD plan description

Servier’s Data Sharing Policy is available at https://clinicaltrials.servier.com/data-request-portal/. Researchers can ask for a study protocol, patient-level and/or study-level clinical study data including clinical study reports. They can ask for all interventional CTs in patients: - Submitted for new medicines and new indications approved after 1 January 2014 in the EEA or the US - Where Servier or an affiliate are the MAH. The date of the first of the new medicine (or the new indication) in one of the EEA Member States will be considered within this scope. Servier’s data sharing policy includes all interventional CTs in patients: - sponsored by Servier, - with a first patient enrolled as of 1 January 2004 onwards, - or New Chemical/Biological Entity (new pharmaceutical form excluded) for which development has been terminated before any MA approval. The datasets generated and/or analysed during the current CT will be available upon request after the MA has been granted.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 1. Be at least 12 years of age and weigh at least 40 kg. 2. Have Grade 2 oligodendroglioma or astrocytoma per WHO 2016 criteria. 3. 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. 4. 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. 5. Have MRI-evaluable, measurable, non-enhancing disease, as confirmed by the BIRC.7. 6. Have a KPS score (for subjects ≥16 years of age) or LPPS score (for subjects <16 years of age) of ≥80%.

Exclusion criteria 1

1. 1. 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. 2. 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).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Radiographic PFS as assessed by the BIRC per modified Response Assessment for Neuro-oncology for Low-Grade Gliomas [RANO-LGG]

Secondary endpoints 5

1. 1. The key secondary endpoint is TTNI.
2. 2.Other secondary efficacy endpoints are TGR, objective response, CR+PR, time to response, time to CR+PR, duration of response, duration of CR+PR, OS, FACT-BR scores, and PFS by investigator.
3. 3. Adverse events, serious adverse events (SAEs), and AEs leading to discontinuation or death, and severity of AEs
4. 4. Safety laboratory parameters, vital signs, 12-lead electrocardiograms (ECGs), evaluation of left ventricular ejection fraction (LVEF), Karnofsky Performance Scale (KPS)/Lansky Play-Performance Scale (LPPS), and concomitant medications.
5. 5. Serial or sparse blood sampling at specified time points for determination of plasma concentration-time profiles and PK parameters of vorasidenib and its circulating metabolite AGI-69460.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Institut De Recherches Internationales Servier IRIS

Sponsor organisation

Institut De Recherches Internationales Servier IRIS

Address

22 Route 128

City

Gif Sur Yvette

Postcode

91190

Country

France

Scientific contact point

Organisation

Institut De Recherches Internationales Servier IRIS

Contact name

Clinical Studies Department

Public contact point

Organisation

Institut De Recherches Internationales Servier IRIS

Contact name

Clinical Studies Department

Third parties 15

Locations

5 EU/EEA countries · 16 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 61 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications