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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04313881




Registration number
NCT04313881
Ethics application status
Date submitted
11/03/2020
Date registered
18/03/2020

Titles & IDs
Public title
Magrolimab + Azacitidine Versus Azacitidine + Placebo in Untreated Participants With Myelodysplastic Syndrome (MDS)
Scientific title
ENHANCE: A Randomized, Double-blind, Multicenter Study Comparing Magrolimab in Combination With Azacitidine Versus Azacitidine Plus Placebo in Treatment-naïve Patients With Higher Risk Myelodysplastic Syndrome
Secondary ID [1] 0 0
2020-004287-26
Secondary ID [2] 0 0
5F9009
Universal Trial Number (UTN)
Trial acronym
ENHANCE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Myelodysplastic Syndromes 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 - Magrolimab
Treatment: Drugs - Azacitidine
Treatment: Drugs - Placebo

Experimental: Magrolimab + Azacitidine - Participants will receive the following magrolimab and azacitidine dosing regimens:

Magrolimab:

Magrolimab Priming Dose:

* 1 mg/kg on Days 1 and 4
* 15 mg/kg on Day 8
* 30 mg/kg on Days 11, 15, followed by weekly administration for 5 doses (on Days 22, 29, 36, 43, and 50)

Magrolimab Maintenance Dose:

* 30 mg/kg on Day 57 and 30 mg/kg every 2 weeks thereafter.

Azacitidine: 75 mg/m\^2 on Days 1 to 7 (or Days 1 to 5 and 8 to 9) of each 28-day cycle.

Placebo comparator: Control Arm (Placebo + Azacitidine) - Participants will receive the following placebo dosing regimens to mirror magrolimab dosing regimen in addition to azacitidine:

Placebo: On Days 1 and 4; Day 8; Days 11, 15, followed by weekly administration for 5 doses (on Days 22, 29, 36, 43, and 50). Additionally, placebo was administered on Day 57 and every 2 weeks thereafter.

Azacitidine: 75 mg/m\^2 on Days 1 to 7 (or Days 1 to 5 and 8 to 9) of each cycle.


Treatment: Drugs: Magrolimab
Administered intravenously

Treatment: Drugs: Azacitidine
Administered either subcutaneously (SC) or intravenously (IV) according to region-specific drug labeling

Treatment: Drugs: Placebo
Placebo to match magrolimab administered intravenously

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

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With Complete Remission (CR)
Timepoint [1] 0 0
From randomization up to 31.01 months
Primary outcome [2] 0 0
Overall Survival (OS)
Timepoint [2] 0 0
From randomization up to 32.62 months
Secondary outcome [1] 0 0
Duration of CR (DOCR)
Timepoint [1] 0 0
From randomization up to 31.01 months
Secondary outcome [2] 0 0
Objective Response Rate (ORR)
Timepoint [2] 0 0
From randomization up to 31.01 months
Secondary outcome [3] 0 0
Duration of Response (DOR)
Timepoint [3] 0 0
From randomization up to 31.01 months
Secondary outcome [4] 0 0
Red Blood Cell (RBC) Transfusion Independence Rate
Timepoint [4] 0 0
From randomization up to 31.01 months
Secondary outcome [5] 0 0
Event Free Survival (EFS)
Timepoint [5] 0 0
From randomization up to 31.01 months
Secondary outcome [6] 0 0
Percentage of Participants With CR in Participants With TP53 Mutation
Timepoint [6] 0 0
From randomization up to 31.01 months
Secondary outcome [7] 0 0
Minimal Residual Disease (MRD)-Negative Response Rate
Timepoint [7] 0 0
From randomization up to 31.01 months
Secondary outcome [8] 0 0
Time to Transformation to AML
Timepoint [8] 0 0
From randomization up to 31.01 months
Secondary outcome [9] 0 0
Progression Free Survival (PFS)
Timepoint [9] 0 0
From randomization up to 31.01 months
Secondary outcome [10] 0 0
Functional Assessment of Cancer Therapy-Anemia (FACT-Anemia) Response Rate
Timepoint [10] 0 0
Up to week 136
Secondary outcome [11] 0 0
Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAE)
Timepoint [11] 0 0
First dose date up to 135.9 weeks plus 70 days (Up to 2.8 years)
Secondary outcome [12] 0 0
Serum Concentration of Magrolimab
Timepoint [12] 0 0
Preinfusion on Days 0, 7, 28, 56, 112, 168, 252 and 336
Secondary outcome [13] 0 0
Percentage of Participants With Positive Anti-magrolimab Antibodies
Timepoint [13] 0 0
Up to 72 hours before administration of any treatment at Day 1, Cycle 1; within 24 hours prior to any study drug administration at Day 1 of Cycles 2, 3, 5, 7, 10, and 13 and End of Treatment (± 7 Days after last study drug dose); Cycle length is 28 Days

Eligibility
Key inclusion criteria
Key

* Participants with Myelodysplastic Syndrome (MDS) defined according to World Health Organization classification, with Revised International Prognostic Scoring System (IPSS-R) prognostic risk category of intermediate, high, or very high risk.
* Adequate performance status and hematological, liver, and kidney function.

Key
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Immediate eligibility for allogenic stem cell transplant (SCT), as determined by the investigator, with an available donor.
* Prior treatment with Cluster of Differentiation (CD) 47 or Signal-regulatory protein alpha (SIRPa)-targeting agents.
* Any prior antileukemic therapy for treatment of intermediate, high, very high risk MDS per IPSS-R.
* Second malignancy, except treated basal cell or localized squamous skin carcinomas, localized prostate cancer, or other malignancies for which participants are not on active anticancer therapies and have had no evidence of active malignancy for at least = 1 year.
* Contraindications to azacitidine.
* Clinical suspicion of active central nervous system (CNS) involvement by MDS.
* Known active or chronic hepatitis B or C infection or human immunodeficiency virus in medical history .
* Active hepatitis B virus and/or active hepatitis C virus, and/or HIV following testing at screening.
* Pregnancy or active breastfeeding.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

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 analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
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
Recruitment state(s)
NSW,QLD,SA,TAS,VIC,WA
Recruitment hospital [1] 0 0
Gosford Hospital - Gosford
Recruitment hospital [2] 0 0
Prince of Wales Hospital - Randwick
Recruitment hospital [3] 0 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [4] 0 0
Westmead Hospital - Westmead
Recruitment hospital [5] 0 0
Icon Cancer Foundation - South Brisbane
Recruitment hospital [6] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [7] 0 0
Flinders Medical Center - Bedford Park
Recruitment hospital [8] 0 0
Royal Hobart Hospital - Hobart
Recruitment hospital [9] 0 0
Eastern Health - Box Hill
Recruitment hospital [10] 0 0
Monash Medical Centre - Clayton
Recruitment hospital [11] 0 0
Peninsula Private Hospital - Frankston
Recruitment hospital [12] 0 0
Barwon Health, University Hospital Geelong - Geelong
Recruitment hospital [13] 0 0
Cabrini Hospital Malvern - Malvern
Recruitment hospital [14] 0 0
The Alfred Hospital - Melbourne
Recruitment hospital [15] 0 0
Royal Melbourne Hospital - Parkville
Recruitment hospital [16] 0 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment postcode(s) [1] 0 0
2250 - Gosford
Recruitment postcode(s) [2] 0 0
2031 - Randwick
Recruitment postcode(s) [3] 0 0
2065 - St Leonards
Recruitment postcode(s) [4] 0 0
2145 - Westmead
Recruitment postcode(s) [5] 0 0
4101 - South Brisbane
Recruitment postcode(s) [6] 0 0
5000 - Adelaide
Recruitment postcode(s) [7] 0 0
5042 - Bedford Park
Recruitment postcode(s) [8] 0 0
7000 - Hobart
Recruitment postcode(s) [9] 0 0
3128 - Box Hill
Recruitment postcode(s) [10] 0 0
3168 - Clayton
Recruitment postcode(s) [11] 0 0
3199 - Frankston
Recruitment postcode(s) [12] 0 0
3220 - Geelong
Recruitment postcode(s) [13] 0 0
3144 - Malvern
Recruitment postcode(s) [14] 0 0
3004 - Melbourne
Recruitment postcode(s) [15] 0 0
3050 - Parkville
Recruitment postcode(s) [16] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
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Alabama
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Arkansas
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California
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Florida
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Georgia
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Illinois
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Kansas
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Louisiana
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Massachusetts
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Michigan
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Missouri
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New York
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North Carolina
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Ohio
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Oklahoma
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Oregon
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Pennsylvania
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South Carolina
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Tennessee
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Texas
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Utah
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Wisconsin
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Austria
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Salzburg
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Vienna
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Turnhout
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Oulu
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Amiens Cedex 1
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Gyor
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Hamilton
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Palmerston North
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Bergen
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Loerenskog
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Oslo
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Stavanger
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Poland
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Krakow
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Lublin
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Poland
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Wroclaw
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Portugal
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Braga
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Lisbon
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Alava
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Barcelona
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Girona
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Spain
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L´Hospitalet de Llobregat
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Spain
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Madrid
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Spain
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Malaga
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Spain
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Pamplona
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Spain
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Salamanca
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Sevilla
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Spain
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Valencia
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Bellinzona
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Bern
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Switzerland
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Zurich
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Turkey
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Ankara
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Inciralt
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Mersin
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Tekirdag
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United Kingdom
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Birmingham
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Boston
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Canterbury
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United Kingdom
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Oxford

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Gilead Sciences
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Gilead Study Director
Address 0 0
Gilead Sciences
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.