The classic website will no longer be available as of June 25, 2024. Please use the modernized ClinicalTrials.gov.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Study of AG-120 (Ivosidenib) vs. Placebo in Combination With Azacitidine in Participants With Previously Untreated Acute Myeloid Leukemia With an IDH1 Mutation (AGILE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03173248
Recruitment Status : Active, not recruiting
First Posted : June 1, 2017
Results First Posted : March 23, 2023
Last Update Posted : April 5, 2024
Sponsor:
Information provided by (Responsible Party):
Servier ( Institut de Recherches Internationales Servier )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Conditions Newly Diagnosed Acute Myeloid Leukemia (AML)
Untreated AML
AML Arising From Myelodysplastic Syndrome (MDS)
Leukemia, Myeloid, Acute
Interventions Drug: AG-120
Drug: Placebo
Drug: Azacitidine
Enrollment 146
Recruitment Details Participants took part in the study at 199 investigational sites from 19 March 2018 to 18 March 2021 (data cut off date). This study is ongoing. Results collected through data cut off date, 18 March 2021 are being reported.
Pre-assignment Details A total of 146 participants with previously untreated isocitrate dehydrogenase 1 mutation-positive (IDH1m) acute myeloid leukemia (AML) were randomized into a 1:1 ratio to receive ivosidenib (AG-120) or AG-120 matched placebo in combination with azacitidine.
Arm/Group Title AG-120 + Azacitidine Placebo + Azacitidine
Hide Arm/Group Description Participants received AG-120 500 mg orally, once daily (QD) in combination with azacitidine 75 milligrams per square meter per day (mg/m^2/day) subcutaneously (SC) or intravenously (IV), on Days 1-7, or on Days 1-5 and 8-9, of each 28-day cycle for a minimum of 6 cycles until death, disease relapse, disease progression, development of unacceptable toxicity (adverse event), confirmed pregnancy, withdrawal by participant or protocol violation. Participants received AG-120 matching placebo orally, QD in combination with azacitidine 75 mg/m^2/day SC or IV, on Days 1-7, or on Days 1-5 and 8-9, of each 28-day cycle for a minimum of 6 cycles until death, disease relapse, disease progression, development of unacceptable toxicity (adverse event), confirmed pregnancy, withdrawal by participant or protocol violation.
Period Title: Overall Study
Started 72 74
Safety Analysis Set [1] 71 73
Completed 0 0
Not Completed 72 74
Reason Not Completed
Death             28             46
Lost to Follow-up             0             1
Withdrawal by Subject             6             4
Ongoing at Data Cut-off Date: 18 March 2021             38             23
[1]
Safety Analysis Set (SAS) included all participants who received at least 1 dose of the study treatment.
Arm/Group Title AG-120 + Azacitidine Placebo + Azacitidine Total
Hide Arm/Group Description Participants received AG-120 500 mg orally, QD in combination with azacitidine 75 mg/m^2/day SC or IV, on Days 1-7, or on Days 1-5 and 8-9, of each 28-day cycle for a minimum of 6 cycles until death, disease relapse, disease progression, development of unacceptable toxicity (adverse event), confirmed pregnancy, withdrawal by participant or protocol violation. Participants received AG-120 matching placebo orally, QD in combination with azacitidine 75 mg/m^2/day SC or IV, on Days 1-7, or on Days 1-5 and 8-9, of each 28-day cycle for a minimum of 6 cycles until death, disease relapse, disease progression, development of unacceptable toxicity (adverse event), confirmed pregnancy, withdrawal by participant or protocol violation. Total of all reporting groups
Overall Number of Baseline Participants 72 74 146
Hide Baseline Analysis Population Description
FAS included all participants who were randomized.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 72 participants 74 participants 146 participants
74.5  (6.18) 75.2  (7.39) 74.8  (6.81)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 72 participants 74 participants 146 participants
Female
30
  41.7%
36
  48.6%
66
  45.2%
Male
42
  58.3%
38
  51.4%
80
  54.8%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 72 participants 74 participants 146 participants
Hispanic or Latino
6
   8.3%
1
   1.4%
7
   4.8%
Not Hispanic or Latino
21
  29.2%
32
  43.2%
53
  36.3%
Unknown or Not Reported
45
  62.5%
41
  55.4%
86
  58.9%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Race Number Analyzed 72 participants 74 participants 146 participants
Asian
15
  20.8%
19
  25.7%
34
  23.3%
White
12
  16.7%
12
  16.2%
24
  16.4%
Black or African American
0
   0.0%
2
   2.7%
2
   1.4%
Other
1
   1.4%
1
   1.4%
2
   1.4%
Not Reported
44
  61.1%
40
  54.1%
84
  57.5%
1.Primary Outcome
Title Event-Free Survival (EFS)
Hide Description EFS was defined as the time from randomization until treatment failure, relapse from remission, or death from any cause, whichever occurs first. Treatment failure was defined as failure to achieve complete remission (CR) by Week 24. CR: Bone marrow blasts <5% and no Auer rods; absence of extramedullary disease; Absolute neutrophil count (ANC) ≥1.0 × 10^9 per litre (10^9/L) (1000 per microlitre [1000/μL]); platelet count ≥100 × 10^9/L (100,000/μL); independence of red blood cell transfusions. Participants who had an EFS event (relapse or death) after, 2 or more missing disease assessments were censored at the last adequate disease assessment documenting no relapse before the missing assessments. The reported data represents the Kaplan-Meier median value.
Time Frame Up to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all participants who were randomized.
Arm/Group Title AG-120 + Azacitidine Placebo + Azacitidine
Hide Arm/Group Description:
Participants received AG-120 500 mg orally, QD in combination with azacitidine 75 mg/m^2/day SC or IV, on Days 1-7, or on Days 1-5 and 8-9, of each 28-day cycle for a minimum of 6 cycles until death, disease relapse, disease progression, development of unacceptable toxicity (adverse event), confirmed pregnancy, withdrawal by participant or protocol violation.
Participants received AG-120 matching placebo orally, QD in combination with azacitidine 75 mg/m^2/day SC or IV, on Days 1-7, or on Days 1-5 and 8-9, of each 28-day cycle for a minimum of 6 cycles until death, disease relapse, disease progression, development of unacceptable toxicity (adverse event), confirmed pregnancy, withdrawal by participant or protocol violation.
Overall Number of Participants Analyzed 72 74
Median (95% Confidence Interval)
Unit of Measure: months
0.03
(0.03 to 11.01)
0.03 [1] 
(NA to NA)
[1]
The upper and lower limit of 95% confidence interval (CI) were not estimable due to low number of participants with events.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection AG-120 + Azacitidine, Placebo + Azacitidine
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0011
Comments P-value is calculated from the one-sided log-rank test stratified by the randomization stratification factors (AML status and geographic region).
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.33
Confidence Interval (2-Sided) 95%
0.16 to 0.69
Estimation Comments Hazard ratio is estimated using a Cox's proportional hazards model stratified by the randomization stratification factors (AML status and geographic region) with placebo + azacitidine as the denominator.
2.Secondary Outcome
Title Complete Remission Rate (CR Rate)
Hide Description CR rate is defined as the proportion of participants who achieve a CR. A Cochran-Mantel-Haenszel (CMH) test will be used to compare CR rate between the 2 treatment arms.
Time Frame Up to approximately 52 months
Outcome Measure Data Not Reported
3.Secondary Outcome
Title Overall Survival (OS)
Hide Description OS is defined as the time from date of randomization to the date of death due to any cause. Kaplan-Meier (KM) curves and KM estimates of OS will be presented for each treatment arm.
Time Frame Up to approximately 52 months
Outcome Measure Data Not Reported
4.Secondary Outcome
Title CR + Complete Remission With Partial Hematologic (CRh) Rate
Hide Description CR + CRh rate is defined as the proportion of participants who achieve a CR or CRh. CRh is defined as a CR with partial recovery of peripheral blood counts (less than 5% bone marrow blasts, absolute neutrophil count (ANC) greater than 0.5 × 10^9/liter (L) 500/microliter (μL)], and platelets greater than 50 × 10^9/L [50,000/μL]). A CMH test will be used to compare the CR + CRh rate between the 2 treatment arms.
Time Frame Up to approximately 52 months
Outcome Measure Data Not Reported
5.Secondary Outcome
Title Objective Response Rate (ORR)
Hide Description ORR is defined as the rate of CR, CR with incomplete hematologic recovery (CRi) (including CR with incomplete platelet recovery [CRp]), partial remission (PR), and morphologic leukemia-free state (MLFS). The best response is calculated using the following hierarchy: CR, followed by CRi (including CRp), followed by PR and MLFS. A summary of best response by treatment arm will be produced. A CMH test will be used to compare ORR between the 2 treatment arms.
Time Frame Up to approximately 52 months
Outcome Measure Data Not Reported
6.Secondary Outcome
Title CR + CRi (Including CRp) Rate
Hide Description The CR + CRi (including CRp) rate is defined as the proportion of participants who achieve a CR or CRi (including CRp). A CMH test will be used to compare the CR + CRi (including CRp) rate between the 2 treatment arms.
Time Frame Up to approximately 52 months
Outcome Measure Data Not Reported
7.Secondary Outcome
Title Duration of CR (DOCR)
Hide Description DOCR will be calculated as the date of the first occurrence of CR to the date of first documented disease relapse, or death. DOCR is only defined for participants who achieve a CR.
Time Frame Up to approximately 52 months
Outcome Measure Data Not Reported
8.Secondary Outcome
Title Duration of CRh (DOCRh)
Hide Description DOCRh will be calculated as the date of the first occurrence of CR or CRh to the date of first documented disease relapse or death. DOCRh is only defined for participants who achieve a CR or CRh.
Time Frame Up to approximately 52 months
Outcome Measure Data Not Reported
9.Secondary Outcome
Title Duration of Response (DOR)
Hide Description DOR will be calculated as the date of the first response to the date of first documented disease relapse, disease progression, or death. DOR is only defined for participants who achieve a CR, CRi (including CRp), PR, and/or MLFS.
Time Frame Up to approximately 52 months
Outcome Measure Data Not Reported
10.Secondary Outcome
Title Duration of CRi (DOCRi)
Hide Description DOCRi will be calculated as the date of the first occurrence of CR or CRi (including CRp) to the date of the first documented relapse or death. DOCRi is only defined for participants who achieve a CR or CRi (including CRp).
Time Frame Up to approximately 52 months
Outcome Measure Data Not Reported
11.Secondary Outcome
Title Time to CR (TTCR)
Hide Description TTCR will be assessed from the date of randomization to the date of first occurrence of CR. TTCR is only defined for participants who achieve a CR.
Time Frame Up to approximately 52 months
Outcome Measure Data Not Reported
12.Secondary Outcome
Title Time to CRh (TTCRh)
Hide Description TTCRh will be assessed from the date of randomization to the date of first occurrence of CR or CRh. TTCRh is only defined for participants who achieve a CR or CRh.
Time Frame Up to approximately 52 months
Outcome Measure Data Not Reported
13.Secondary Outcome
Title Time to Response (TTR)
Hide Description TTR will be assessed from the date of randomization to the date of the first response. TTR is only defined for participants who achieve a CR, CRi (including CRp), PR, and/or MLFS.
Time Frame Up to approximately 52 months
Outcome Measure Data Not Reported
14.Secondary Outcome
Title Time to CRi (TTCRi)
Hide Description TTCRi will be assessed from the date of randomization to the date of first occurrence of CR or CRi (including CRp). TTCRi is only defined for participants who achieve a CR or CRi (including CRp).
Time Frame Up to approximately 52 months
Outcome Measure Data Not Reported
15.Secondary Outcome
Title Percentage of Participants With Abnormalities in Vital Sign Measurements
Hide Description Vital signs will include body temperature, respiratory rate, blood pressure, and heart rate.
Time Frame Up to approximately 52 months
Outcome Measure Data Not Reported
16.Secondary Outcome
Title Percentage of Participants With Abnormalities in Eastern Cooperative Oncology Group Performance Status (ECOG PS)
Hide Description [Not Specified]
Time Frame Up to approximately 52 months
Outcome Measure Data Not Reported
17.Secondary Outcome
Title Percentage of Participants With Abnormalities in 12-lead Electrocardiograms (ECGs)
Hide Description [Not Specified]
Time Frame Up to approximately 52 months
Outcome Measure Data Not Reported
18.Secondary Outcome
Title Percentage of Participants With Abnormalities in Echocardiogram (ECHO) or Multi-Gated Acquisition (MUGA) for Left Ventricular Ejection Fraction (LVEF)
Hide Description LVEF is determined by ECHO or MUGA scan in participants.
Time Frame Up to approximately 52 months
Outcome Measure Data Not Reported
19.Secondary Outcome
Title Percentage of Participants With Abnormalities in Clinical Laboratory Tests
Hide Description Clinical laboratory assessments will include hematology, serum chemistry, coagulation.
Time Frame Up to approximately 52 months
Outcome Measure Data Not Reported
20.Secondary Outcome
Title Percentage of Participants With Adverse Events (AEs)
Hide Description An AE is defined as any untoward medical occurrence in a clinical investigation participant administered an investigational medicinal product; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug.
Time Frame Up to approximately 52 months
Outcome Measure Data Not Reported
21.Secondary Outcome
Title Percentage of Participants With AEs of Special Interest (AESIs)
Hide Description AESIs are AEs that are not solicited local or systemic AEs, they are predefined AEs that required close monitoring and prompt reporting to the sponsor. AESIs include protocol-specified QT prolongation, isocitrate dehydrogenase (IDH) differentiation syndrome and leukocytosis.
Time Frame Up to approximately 52 months
Outcome Measure Data Not Reported
22.Secondary Outcome
Title Percentage of Participants With Serious Adverse Events (SAEs)
Hide Description An SAE is defined as an untoward medical occurrence, significant hazard, contraindication, side effect or precaution that at any dose: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.
Time Frame Up to approximately 52 months
Outcome Measure Data Not Reported
23.Secondary Outcome
Title Percentage of Participants With Adverse Events Leading to Discontinuation or Death
Hide Description An AE is defined as any untoward medical occurrence in a clinical investigation participant administered an investigational medicinal product; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug.
Time Frame Up to approximately 52 months
Outcome Measure Data Not Reported
24.Secondary Outcome
Title Percentage of Participants Using Concomitant Medications
Hide Description Participants receiving concomitant medications will be adequately monitored by ECG controls, drug concentration (where applicable), and serum electrolytes (i.e., potassium and magnesium).
Time Frame Up to approximately 52 months
Outcome Measure Data Not Reported
25.Secondary Outcome
Title Units of Platelets and Red Blood Cells (RBC) Infused
Hide Description All measures that are indicative of clinical benefit are measured like number of units of platelet and RBC infused.
Time Frame Up to approximately 52 months
Outcome Measure Data Not Reported
26.Secondary Outcome
Title Rate of Infection
Hide Description [Not Specified]
Time Frame Up to approximately 52 months
Outcome Measure Data Not Reported
27.Secondary Outcome
Title Number of Days Spent Hospitalized
Hide Description [Not Specified]
Time Frame Up to approximately 52 months
Outcome Measure Data Not Reported
28.Secondary Outcome
Title Change From Baseline in the European Organisation for Research and Treatment of Cancer (EORTC) QLC-C30 Questionnaire
Hide Description The EORTC QLQ-C30 questionnaire measures quality of life and consists of 30 questions that are incorporated into 5 functional domains (physical, role, cognitive, emotional, and social); a global health status/global quality of life; 3 symptom scales (fatigue, pain, and nausea and vomiting); and 6 single items that assess additional symptoms (dyspnea, appetite loss, sleep disturbance, constipation, and diarrhea) and the perceived financial burden of treatment experienced by participants with cancer.
Time Frame Up to approximately 52 months
Outcome Measure Data Not Reported
29.Secondary Outcome
Title Change From Baseline in the EORTC EQ-5D-5L Questionnaire
Hide Description The EORTC EQ-5D-5L questionnaire measures quality of life and spans 5 dimensions, including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression, which are used to build a composite of the participant's health status.
Time Frame Up to approximately 52 months
Outcome Measure Data Not Reported
30.Secondary Outcome
Title Percentage of Participants With CR With IDH1 Mutation Clearance (MC)
Hide Description CR with IDH1 MC is defined as a response of CR where there is no evidence of the IDH1 mutation by molecular techniques to below the level of detection (0.02%-0.04%) for ≥1 on-treatment time point. A CMH test will be used to compare the rate of CR between 2 treatment arms.
Time Frame Up to approximately 52 months
Outcome Measure Data Not Reported
31.Secondary Outcome
Title Percentage of Participants With Drug Exposure, Dose Modifications and Dose Intensities
Hide Description The number of doses administered, total dose, duration of treatment, dose intensity, and the proportion of participants with dose modifications, will be summarized by treatment arm.
Time Frame Up to approximately 52 months
Outcome Measure Data Not Reported
32.Secondary Outcome
Title Circulating Plasma Concentration of AG-120
Hide Description Serial blood samples will be drawn before and after dosing of study treatment in order to determine circulating plasma concentrations.
Time Frame Up to approximately 52 months
Outcome Measure Data Not Reported
33.Secondary Outcome
Title Circulating Plasma Concentration of 2-HG
Hide Description Serial blood samples will be drawn before and after dosing of study treatment in order to determine circulating plasma concentrations.
Time Frame Up to approximately 52 months
Outcome Measure Data Not Reported
Time Frame 3 years
Adverse Event Reporting Description SAS included all participants who received at least 1 dose of the study treatment.
 
Arm/Group Title AG-120 + Azacitidine Placebo + Azacitidine
Hide Arm/Group Description Participants received AG-120 500 mg orally, QD in combination with azacitidine 75 mg/m^2/day SC or IV, on Days 1-7, or on Days 1-5 and 8-9, of each 28-day cycle for a minimum of 6 cycles until death, disease relapse, disease progression, development of unacceptable toxicity (adverse event), confirmed pregnancy, withdrawal by participant or protocol violation. Participants received AG-120 matching placebo orally, QD in combination with azacitidine 75 mg/m^2/day SC or IV, on Days 1-7, or on Days 1-5 and 8-9, of each 28-day cycle for a minimum of 6 cycles until death, disease relapse, disease progression, development of unacceptable toxicity (adverse event), confirmed pregnancy, withdrawal by participant or protocol violation.
All-Cause Mortality
AG-120 + Azacitidine Placebo + Azacitidine
Affected / at Risk (%) Affected / at Risk (%)
Total   27/71 (38.03%)   45/73 (61.64%) 
Hide Serious Adverse Events
AG-120 + Azacitidine Placebo + Azacitidine
Affected / at Risk (%) Affected / at Risk (%)
Total   49/71 (69.01%)   60/73 (82.19%) 
Blood and lymphatic system disorders     
Febrile neutropenia † 1  17/71 (23.94%)  20/73 (27.40%) 
Thrombocytopenia † 1  2/71 (2.82%)  1/73 (1.37%) 
Febrile bone marrow aplasia † 1  1/71 (1.41%)  1/73 (1.37%) 
Neutropenia † 1  1/71 (1.41%)  0/73 (0.00%) 
Bicytopenia † 1  0/71 (0.00%)  1/73 (1.37%) 
Splenomegaly † 1  0/71 (0.00%)  1/73 (1.37%) 
Cardiac disorders     
Atrial fibrillation † 1  1/71 (1.41%)  1/73 (1.37%) 
Atrial thrombosis † 1  1/71 (1.41%)  0/73 (0.00%) 
Cardiac failure † 1  1/71 (1.41%)  0/73 (0.00%) 
Pericardial effusion † 1  1/71 (1.41%)  0/73 (0.00%) 
Arrhythmia † 1  0/71 (0.00%)  1/73 (1.37%) 
Atrial flutter † 1  0/71 (0.00%)  1/73 (1.37%) 
Eye disorders     
Diplopia † 1  0/71 (0.00%)  1/73 (1.37%) 
Gastrointestinal disorders     
Colitis ischaemic † 1  1/71 (1.41%)  0/73 (0.00%) 
Diverticular perforation † 1  1/71 (1.41%)  1/73 (1.37%) 
Lower gastrointestinal haemorrhage † 1  1/71 (1.41%)  0/73 (0.00%) 
Vomiting † 1  1/71 (1.41%)  0/73 (0.00%) 
Colitis † 1  0/71 (0.00%)  1/73 (1.37%) 
Diarrhoea † 1  0/71 (0.00%)  2/73 (2.74%) 
Haemorrhoids † 1  0/71 (0.00%)  1/73 (1.37%) 
Neutropenic colitis † 1  0/71 (0.00%)  1/73 (1.37%) 
Upper gastrointestinal haemorrhage † 1  0/71 (0.00%)  1/73 (1.37%) 
General disorders     
Pyrexia † 1  4/71 (5.63%)  3/73 (4.11%) 
Fatigue † 1  1/71 (1.41%)  0/73 (0.00%) 
Multiple organ dysfunction syndrome † 1  1/71 (1.41%)  1/73 (1.37%) 
Pain † 1  1/71 (1.41%)  0/73 (0.00%) 
Asthenia † 1  0/71 (0.00%)  1/73 (1.37%) 
General physical health deterioration † 1  0/71 (0.00%)  2/73 (2.74%) 
Infections and infestations     
Pneumonia † 1  14/71 (19.72%)  16/73 (21.92%) 
Bronchopulmonary aspergillosis † 1  2/71 (2.82%)  2/73 (2.74%) 
COVID-19 † 1  2/71 (2.82%)  0/73 (0.00%) 
Appendicitis † 1  1/71 (1.41%)  0/73 (0.00%) 
Bacterial sepsis † 1  1/71 (1.41%)  0/73 (0.00%) 
Clostridium difficile colitis † 1  1/71 (1.41%)  1/73 (1.37%) 
Enterococcal infection † 1  1/71 (1.41%)  1/73 (1.37%) 
Escherichia sepsis † 1  1/71 (1.41%)  1/73 (1.37%) 
Infection † 1  1/71 (1.41%)  0/73 (0.00%) 
Metapneumovirus infection † 1  1/71 (1.41%)  0/73 (0.00%) 
Pneumonia fungal † 1  1/71 (1.41%)  1/73 (1.37%) 
Pneumonia pseudomonal † 1  1/71 (1.41%)  1/73 (1.37%) 
Pneumonia respiratory syncytial viral † 1  1/71 (1.41%)  0/73 (0.00%) 
Pseudomonas infection † 1  1/71 (1.41%)  0/73 (0.00%) 
Respiratory syncytial virus infection † 1  1/71 (1.41%)  0/73 (0.00%) 
Sepsis † 1  1/71 (1.41%)  3/73 (4.11%) 
Septic shock † 1  1/71 (1.41%)  2/73 (2.74%) 
Sinusitis † 1  1/71 (1.41%)  0/73 (0.00%) 
Skin infection † 1  1/71 (1.41%)  0/73 (0.00%) 
Urinary tract infection † 1  1/71 (1.41%)  0/73 (0.00%) 
Abdominal infection † 1  0/71 (0.00%)  1/73 (1.37%) 
Abscess limb † 1  0/71 (0.00%)  1/73 (1.37%) 
Anal abscess † 1  0/71 (0.00%)  2/73 (2.74%) 
Aspergillus infection † 1  0/71 (0.00%)  1/73 (1.37%) 
Bacteraemia † 1  0/71 (0.00%)  1/73 (1.37%) 
Bronchitis † 1  0/71 (0.00%)  1/73 (1.37%) 
COVID-19 pneumonia † 1  0/71 (0.00%)  1/73 (1.37%) 
Corynebacterium sepsis † 1  0/71 (0.00%)  1/73 (1.37%) 
Diverticulitis † 1  0/71 (0.00%)  2/73 (2.74%) 
Enterococcal sepsis † 1  0/71 (0.00%)  1/73 (1.37%) 
Influenza † 1  0/71 (0.00%)  1/73 (1.37%) 
Lower respiratory tract infection † 1  0/71 (0.00%)  1/73 (1.37%) 
Parotitis † 1  0/71 (0.00%)  2/73 (2.74%) 
Perirectal abscess † 1  0/71 (0.00%)  1/73 (1.37%) 
Pneumocystis jirovecii pneumonia † 1  0/71 (0.00%)  1/73 (1.37%) 
Pneumonia bacterial † 1  0/71 (0.00%)  1/73 (1.37%) 
Pneumonia staphylococcal † 1  0/71 (0.00%)  1/73 (1.37%) 
Pseudomonal sepsis † 1  0/71 (0.00%)  1/73 (1.37%) 
Respiratory tract infection fungal † 1  0/71 (0.00%)  1/73 (1.37%) 
Soft tissue infection † 1  0/71 (0.00%)  1/73 (1.37%) 
Tonsillitis † 1  0/71 (0.00%)  1/73 (1.37%) 
Upper respiratory tract infection † 1  0/71 (0.00%)  1/73 (1.37%) 
Urinary tract infection enterococcal † 1  0/71 (0.00%)  1/73 (1.37%) 
Injury, poisoning and procedural complications     
Femur fracture † 1  1/71 (1.41%)  0/73 (0.00%) 
Abdominal wound dehiscence † 1  0/71 (0.00%)  1/73 (1.37%) 
Post lumbar puncture syndrome † 1  0/71 (0.00%)  1/73 (1.37%) 
Traumatic intracranial haemorrhage † 1  0/71 (0.00%)  1/73 (1.37%) 
Investigations     
Blast cell count increased † 1  1/71 (1.41%)  0/73 (0.00%) 
Blood fibrinogen decreased † 1  1/71 (1.41%)  0/73 (0.00%) 
White blood cell count increased † 1  1/71 (1.41%)  0/73 (0.00%) 
C-reactive protein increased † 1  0/71 (0.00%)  1/73 (1.37%) 
Weight decreased † 1  0/71 (0.00%)  1/73 (1.37%) 
White blood cell count decreased † 1  0/71 (0.00%)  1/73 (1.37%) 
Metabolism and nutrition disorders     
Decreased appetite † 1  0/71 (0.00%)  1/73 (1.37%) 
Musculoskeletal and connective tissue disorders     
Chondrocalcinosis pyrophosphate † 1  1/71 (1.41%)  0/73 (0.00%) 
Pain in extremity † 1  1/71 (1.41%)  0/73 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Differentiation syndrome † 1  6/71 (8.45%)  1/73 (1.37%) 
Adenocarcinoma † 1  1/71 (1.41%)  0/73 (0.00%) 
Lung adenocarcinoma † 1  1/71 (1.41%)  0/73 (0.00%) 
Lung neoplasm malignant † 1  1/71 (1.41%)  0/73 (0.00%) 
Adenocarcinoma of colon † 1  0/71 (0.00%)  1/73 (1.37%) 
Nervous system disorders     
Haemorrhage intracranial † 1  2/71 (2.82%)  0/73 (0.00%) 
Cerebral infarction † 1  1/71 (1.41%)  0/73 (0.00%) 
Cerebral ischaemia † 1  1/71 (1.41%)  0/73 (0.00%) 
Ischaemic stroke † 1  1/71 (1.41%)  0/73 (0.00%) 
Seizure † 1  1/71 (1.41%)  0/73 (0.00%) 
Dementia † 1  0/71 (0.00%)  1/73 (1.37%) 
Presyncope † 1  0/71 (0.00%)  1/73 (1.37%) 
Syncope † 1  0/71 (0.00%)  1/73 (1.37%) 
Psychiatric disorders     
Delirium † 1  0/71 (0.00%)  1/73 (1.37%) 
Renal and urinary disorders     
Renal failure † 1  2/71 (2.82%)  1/73 (1.37%) 
Acute kidney injury † 1  1/71 (1.41%)  0/73 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Pulmonary embolism † 1  3/71 (4.23%)  1/73 (1.37%) 
Pleural effusion † 1  2/71 (2.82%)  0/73 (0.00%) 
Hypoxia † 1  1/71 (1.41%)  0/73 (0.00%) 
Pneumonitis † 1  1/71 (1.41%)  0/73 (0.00%) 
Respiratory failure † 1  1/71 (1.41%)  1/73 (1.37%) 
Acute respiratory failure † 1  0/71 (0.00%)  1/73 (1.37%) 
Dyspnoea † 1  0/71 (0.00%)  1/73 (1.37%) 
Epistaxis † 1  0/71 (0.00%)  2/73 (2.74%) 
Lung disorder † 1  0/71 (0.00%)  1/73 (1.37%) 
Pulmonary oedema † 1  0/71 (0.00%)  1/73 (1.37%) 
Skin and subcutaneous tissue disorders     
Rash † 1  1/71 (1.41%)  0/73 (0.00%) 
Vascular disorders     
Hypertension † 1  0/71 (0.00%)  1/73 (1.37%) 
1
Term from vocabulary, MedDRA (23.1)
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
AG-120 + Azacitidine Placebo + Azacitidine
Affected / at Risk (%) Affected / at Risk (%)
Total   68/71 (95.77%)   72/73 (98.63%) 
Blood and lymphatic system disorders     
Anaemia † 1  22/71 (30.99%)  21/73 (28.77%) 
Febrile neutropenia † 1  7/71 (9.86%)  9/73 (12.33%) 
Leukocytosis † 1  8/71 (11.27%)  1/73 (1.37%) 
Leukopenia † 1  6/71 (8.45%)  2/73 (2.74%) 
Neutropenia † 1  20/71 (28.17%)  12/73 (16.44%) 
Thrombocytopenia † 1  20/71 (28.17%)  14/73 (19.18%) 
Gastrointestinal disorders     
Abdominal pain † 1  6/71 (8.45%)  7/73 (9.59%) 
Constipation † 1  19/71 (26.76%)  38/73 (52.05%) 
Diarrhoea † 1  25/71 (35.21%)  25/73 (34.25%) 
Haemorrhoids † 1  5/71 (7.04%)  7/73 (9.59%) 
Nausea † 1  30/71 (42.25%)  28/73 (38.36%) 
Proctalgia † 1  1/71 (1.41%)  5/73 (6.85%) 
Stomatitis † 1  0/71 (0.00%)  5/73 (6.85%) 
Vomiting † 1  28/71 (39.44%)  19/73 (26.03%) 
General disorders     
Asthenia † 1  11/71 (15.49%)  24/73 (32.88%) 
Chest discomfort † 1  2/71 (2.82%)  4/73 (5.48%) 
Fatigue † 1  9/71 (12.68%)  10/73 (13.70%) 
Injection site reaction † 1  4/71 (5.63%)  5/73 (6.85%) 
Non-cardiac chest pain † 1  4/71 (5.63%)  2/73 (2.74%) 
Oedema peripheral † 1  8/71 (11.27%)  16/73 (21.92%) 
Pyrexia † 1  23/71 (32.39%)  29/73 (39.73%) 
Infections and infestations     
Oral candidiasis † 1  1/71 (1.41%)  5/73 (6.85%) 
Oral herpes † 1  4/71 (5.63%)  3/73 (4.11%) 
Pneumonia † 1  8/71 (11.27%)  9/73 (12.33%) 
Suspected COVID-19 † 1  0/71 (0.00%)  4/73 (5.48%) 
Upper respiratory tract infection † 1  4/71 (5.63%)  3/73 (4.11%) 
Urinary tract infection † 1  3/71 (4.23%)  7/73 (9.59%) 
Injury, poisoning and procedural complications     
Fall † 1  3/71 (4.23%)  4/73 (5.48%) 
Investigations     
Blood alkaline phosphatase increased † 1  1/71 (1.41%)  4/73 (5.48%) 
Blood creatinine increased † 1  4/71 (5.63%)  3/73 (4.11%) 
C-reactive protein increased † 1  3/71 (4.23%)  4/73 (5.48%) 
Electrocardiogram QT prolonged † 1  14/71 (19.72%)  5/73 (6.85%) 
Neutrophil count decreased † 1  6/71 (8.45%)  5/73 (6.85%) 
Platelet count decreased † 1  8/71 (11.27%)  6/73 (8.22%) 
Weight decreased † 1  4/71 (5.63%)  11/73 (15.07%) 
Metabolism and nutrition disorders     
Decreased appetite † 1  11/71 (15.49%)  19/73 (26.03%) 
Hyperglycaemia † 1  1/71 (1.41%)  6/73 (8.22%) 
Hyperkalaemia † 1  4/71 (5.63%)  2/73 (2.74%) 
Hyperuricaemia † 1  2/71 (2.82%)  7/73 (9.59%) 
Hypoglycaemia † 1  1/71 (1.41%)  4/73 (5.48%) 
Hypokalaemia † 1  11/71 (15.49%)  21/73 (28.77%) 
Hypomagnesaemia † 1  5/71 (7.04%)  5/73 (6.85%) 
Hyponatraemia † 1  5/71 (7.04%)  7/73 (9.59%) 
Hypophosphataemia † 1  2/71 (2.82%)  5/73 (6.85%) 
Musculoskeletal and connective tissue disorders     
Arthralgia † 1  8/71 (11.27%)  3/73 (4.11%) 
Back pain † 1  6/71 (8.45%)  2/73 (2.74%) 
Bone pain † 1  4/71 (5.63%)  4/73 (5.48%) 
Pain in extremity † 1  9/71 (12.68%)  3/73 (4.11%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Differentiation syndrome † 1  5/71 (7.04%)  5/73 (6.85%) 
Nervous system disorders     
Dizziness † 1  7/71 (9.86%)  3/73 (4.11%) 
Dysgeusia † 1  1/71 (1.41%)  4/73 (5.48%) 
Headache † 1  8/71 (11.27%)  2/73 (2.74%) 
Syncope † 1  5/71 (7.04%)  4/73 (5.48%) 
Psychiatric disorders     
Anxiety † 1  5/71 (7.04%)  3/73 (4.11%) 
Confusional state † 1  5/71 (7.04%)  5/73 (6.85%) 
Delirium † 1  0/71 (0.00%)  4/73 (5.48%) 
Insomnia † 1  13/71 (18.31%)  9/73 (12.33%) 
Renal and urinary disorders     
Acute kidney injury † 1  3/71 (4.23%)  5/73 (6.85%) 
Respiratory, thoracic and mediastinal disorders     
Cough † 1  6/71 (8.45%)  11/73 (15.07%) 
Dyspnoea † 1  11/71 (15.49%)  9/73 (12.33%) 
Epistaxis † 1  7/71 (9.86%)  5/73 (6.85%) 
Oropharyngeal pain † 1  6/71 (8.45%)  1/73 (1.37%) 
Pleural effusion † 1  2/71 (2.82%)  6/73 (8.22%) 
Skin and subcutaneous tissue disorders     
Dry skin † 1  4/71 (5.63%)  2/73 (2.74%) 
Erythema † 1  6/71 (8.45%)  3/73 (4.11%) 
Petechiae † 1  4/71 (5.63%)  1/73 (1.37%) 
Pruritus † 1  7/71 (9.86%)  4/73 (5.48%) 
Rash † 1  6/71 (8.45%)  9/73 (12.33%) 
Rash maculo-papular † 1  0/71 (0.00%)  4/73 (5.48%) 
Vascular disorders     
Haematoma † 1  9/71 (12.68%)  1/73 (1.37%) 
Hypertension † 1  7/71 (9.86%)  4/73 (5.48%) 
Hypotension † 1  4/71 (5.63%)  5/73 (6.85%) 
1
Term from vocabulary, MedDRA (23.1)
†
Indicates events were collected by systematic assessment
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Clinical Studies Department
Organization: Institut de Recherches Internationales Servier (I.R.I.S.)
Phone: +33155726000
EMail: scientificinformation@servier.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Servier ( Institut de Recherches Internationales Servier )
ClinicalTrials.gov Identifier: NCT03173248    
Other Study ID Numbers: AG120-C-009
First Submitted: May 30, 2017
First Posted: June 1, 2017
Results First Submitted: February 22, 2023
Results First Posted: March 23, 2023
Last Update Posted: April 5, 2024