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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04401748




Registration number
NCT04401748
Ethics application status
Date submitted
22/05/2020
Date registered
26/05/2020
Date last updated
2/12/2020

Titles & IDs
Public title
Safety And Efficacy Study Of Venetoclax Tablet With Intravenous or Subcutaneous Azacitidine to Assess Change in Complete Remission and Overall Survival In Adult Participants With Newly Diagnosed Higher-Risk Myelodysplastic Syndrome
Scientific title
A Randomized, Double-Blind, Phase 3 Study Evaluating the Safety and Efficacy of Venetoclax in Combination With Azacitidine in Patients Newly Diagnosed With Higher-Risk Myelodysplastic Syndrome (Higher-Risk MDS)
Secondary ID [1] 0 0
2020-000744-55
Secondary ID [2] 0 0
M15-954
Universal Trial Number (UTN)
Trial acronym
Verona
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Myelodysplastic Syndrome (MDS) 0 0
Condition category
Condition code
Blood 0 0 0 0
Haematological diseases
Blood 0 0 0 0
Other blood disorders
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Venetoclax
Treatment: Drugs - Azacitidine
Treatment: Drugs - Placebo

Experimental: Arm 1: Venetoclax + Azacitidine (AZA) - Participants will receive venetoclax once daily (QD) (Days 1-14) in combination with AZA QD (Days 1-7) of each 28 day cycle.

Active Comparator: Arm 2: Placebo + Azacitidine - Participants will receive placebo once daily (QD) (Days 1-14) in combination with AZA QD (Days 1-7) of each 28 day cycle.


Treatment: Drugs: Venetoclax
Tablet: Oral

Treatment: Drugs: Azacitidine
Subcutaneous (SC) or Intravenous (IV) injection

Treatment: Drugs: Placebo
Tablet; Oral

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Complete Remission (CR) - CR is defined as achieving a complete remission at any time point during the study per the modified International Working Group (IWG) 2006 criteria for myelodysplastic syndrome (MDS).
Timepoint [1] 0 0
Up To 36 Months
Primary outcome [2] 0 0
Overall survival (OS) - OS is defined as the number of days from the date of randomization to the date of death of any cause, or last known date to be alive.
Timepoint [2] 0 0
Up To 5 Years
Secondary outcome [1] 0 0
Percentage of Participants who Achieve Red Blood Cell (RBC) transfusion independence (TI) - RBC TI is when the participants who were transfusion dependent at baseline achieve transfusion independence post baseline. RBC TI is a period of at least 56 days with no transfusion after the date of the first dose of study drug to the last dose of study drug + 30 days, the initiation of post-treatment therapy, or death, whichever is earliest.
Timepoint [1] 0 0
Up To 5 Years
Secondary outcome [2] 0 0
Percentage of Participants who Achieve Platelet Transfusion Independence (TI) - Platelet TI is when participants who were transfusion dependent at baseline achieve transfusion independence post baseline. Platelet TI is a period of at least 56 days with no transfusion after the date of the first dose of study drug to the last dose of study drug + 30 days, the initiation of post-treatment therapy, or death, whichever is earliest.
Timepoint [2] 0 0
Up To 5 Years
Secondary outcome [3] 0 0
Change in Patient-Reported Outcomes Measurement Information System (PROMIS)-Fatigue Short Form (SF) 7a Scale Score - Fatigue will be assessed using the PROMIS Fatigue SF 7a Global Fatigue Score. PROMIS Fatigue SF 7a is a 7-item questionnaire that assesses the impact and experience of fatigue over the past 7 days. Participants rate items on a 5-point scale, with 1 as "never" an 5 as "always".
Timepoint [3] 0 0
Up To 5 Years
Secondary outcome [4] 0 0
Time to Deterioration in Physical Functioning as Measured by Physical Functioning Domain of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Scale - Time to deterioration in physical functioning, as measured by the EORTC QLQ-C30 physical functioning score is defined as the time from the date of randomization to the date of death of any cause, or the first time worsening of score from baseline >= a pre-specified threshold. Participants rate items on a 4-point scale, with 1 as "not at all" and 4 as "very much."
Timepoint [4] 0 0
Up To 5 Years
Secondary outcome [5] 0 0
Overall Response (OR) - OR [complete remission (CR) + partial response (PR)] is defined as achieving a CR or PR at any time point during the study per the modified IWG 2006 criteria for MDS.
Timepoint [5] 0 0
Up To 5 Years
Secondary outcome [6] 0 0
Modified Overall Response (mOR) - mOR [complete remission (CR) + marrow complete remission (mCR) + partial response (PR)] is defined as achieving a CR, mCR, or PR at any time point during the study per the modified IWG 2006 criteria for MDS.
Timepoint [6] 0 0
Up To 5 Years

Eligibility
Key inclusion criteria
- Participants with a diagnosis of Myelodysplastic Syndrome (MDS) according to the 2016
World Health Organization (WHO) classification wtih presence of < 20% bone marrow
blasts per marrow biopsy/aspirate at screening.

- Participants must meet the following disease activity criteria:

1. Overall Revised International Prognostic Scoring System (IPSS-R) score > 3
(intermediate, high or very high).

2. Eastern Cooperative Oncology Group (ECOG) performance status of <= 2.

3. Hematopoietic stem cell transplant (HSCT) eligible with no pre-arranged HSCT at
the time of Study Day 1, or HSCT ineligible without plan for HSCT at the time of
Study Day 1.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Prior therapy for MDS with any hypomethylating agent, chemotherapy, or allogenic stem
cell transplantation.

- Prior diagnosis of therapy-related MDS (t-MDS), MDS evolving from a pre-existing
myeloproliferative neoplasm (MPN), MDS/MPN including chronic myelomonocytic leukemia
(CMML), atypical chronic myeloid leukemia (aCML), juvenile myelomonocytic leukemia
(JMML) and unclassifiable MDS/MPN.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
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Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
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NSW,QLD,SA,VIC
Recruitment hospital [1] 0 0
St George Hospital /ID# 221810 - Kogarah
Recruitment hospital [2] 0 0
Gold Coast University Hospital /ID# 222606 - Southport
Recruitment hospital [3] 0 0
Royal Adelaide Hospital /ID# 221805 - Adelaide
Recruitment hospital [4] 0 0
St. Vincents Hosp Melbourne /ID# 221809 - Fitzroy
Recruitment hospital [5] 0 0
Austin Hospital /ID# 221807 - Heidelberg
Recruitment postcode(s) [1] 0 0
2217 - Kogarah
Recruitment postcode(s) [2] 0 0
4215 - Southport
Recruitment postcode(s) [3] 0 0
5000 - Adelaide
Recruitment postcode(s) [4] 0 0
3065 - Fitzroy
Recruitment postcode(s) [5] 0 0
3084 - Heidelberg
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
AbbVie
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Genentech, Inc.
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Myelodysplastic Syndrome (MDS) is a group of disorders that gradually affect the ability of a
person's bone marrow (semi-liquid tissue present in many bones like backbones) to produce
normal blood cells. Some people with MDS have a risk of the disease progressing to acute
myeloid leukemia (AML), and a risk of death from the disease itself. Symptoms of MDS include
fatigue, shortness of breath, unusual paleness due to anemia (low red blood cell count), easy
or unusual bruising, and red spots just beneath the skin caused by bleeding. The purpose of
this study is to see how safe and effective venetoclax and azacitidine (AZA) combination are
when compared to AZA and a placebo (contains no medicine), in participants with newly
diagnosed higher-risk MDS.

Venetoclax is an investigational drug being developed for the treatment of MDS. The study
consists of two treatment arms - In one arm, participants will receive venetoclax and AZA. In
another arm, participants will receive AZA and placebo. Adult participants with newly
diagnosed higher-risk MDS will be enrolled. Around 500 participants will be enrolled in
approximately 200 sites worldwide.

Participants in one arm will receive oral doses of venetoclax tablet and intravenous
(infusion in the vein) or subcutaneous (given under the skin) AZA solution. Participants in
another arm will receive oral doses of placebo tablet and intravenous or subcutaneous AZA
solution.

There may be higher treatment burden for participants in this trial compared to their
standard of care. Participants will attend regular visits during the course of the study at a
hospital or clinic. The effect of the treatment will be checked by medical assessments, blood
and bone marrow tests, checking for side effects, and completing questionnaires.
Trial website
https://clinicaltrials.gov/show/NCT04401748
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
AbbVie Inc.
Address 0 0
AbbVie
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
ABBVIE CALL CENTER
Address 0 0
Country 0 0
Phone 0 0
844-663-3742
Fax 0 0
Email 0 0
abbvieclinicaltrials@abbvie.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04401748