A Phase 3, Multi-Center, Randomized, Double-Blind, Placeb... | NCT03764618

NCT03764618

Status Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Fostamatinib	Experimental	Initial dose is 100 mg by mouth (PO) twice a day (bid). At week 4 dose will be increased to fostamatinib 150 mg PO bid if subjects have adequately tolerated the study drug in the opinion of the Investigator.	Drug: Fostamatinib disodium
Placebo	Placebo Comparator	Initial dose is 100 mg by mouth (PO) twice a day (bid). At week 4 dose will be increased to placebo 150 mg PO bid if subjects have adequately tolerated the study drug in the opinion of the Investigator.	Drug: Placebo

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Fostamatinib disodium	Drug	Fostamatinib (100mg PO bid or 150 mg PO bid) The dose may be reduced at any time to a dose as low as fostamatinib 100 mg PO qd or matching placebo if dose limiting adverse events are observed.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Durable Hemoglobin Response	Proportion of subjects achieving a hemoglobin level ≥ 10 g/dL with an increase from Baseline in hemoglobin level of ≥ 2 g/dL on 3 consecutive available visits during the 24-week treatment period.	24 Weeks

Secondary Outcomes

Measure	Description	Time Frame
A Hemoglobin Response by Week 24	Proportion of subjects with a hemoglobin response by Week 24.	24 weeks
Change From Baseline in Hemoglobin Level of 2 g/dL or Greater	Proportion of subjects with change from baseline in hemoglobin level of 2 g/dL or greater.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Subject must have a diagnosis of primary or secondary warm Antibody Autoimmune Hemolytic Anemia (wAIHA) as documented by a positive direct antiglobulin test (DAT) specific for anti-IgG or anti-IgA.
Have failed or not tolerated at least one prior wAIHA treatment regimen, including steroids, rituximab, azathioprine, cyclophosphamide, cyclosporine, MMF, danazol, vincristine, ESA or splenectomy (folate, iron or other supplements do not fulfill this criterion).
Have haptoglobin <LLN or total bilirubin >ULN or lactate dehydrogenase (LDH) >ULN.
At screening, subject's hemoglobin level must be ≤9 g/dL OR if hemoglobin value >9 g/dL and <10 g/dL, subject must be on an allowed wAIHA treatment AND the subject must have documented symptoms related to anemia (e.g., weakness, dizziness, fatigue, shortness of breath, chest pain).
Karnofsky performance status (KPS) ≥70.
Subject's concurrent treatment for wAIHA may consist of no more than two of any of the following agents: azathioprine, steroids, ESAs, mycophenolate mofetil, dapsone or danazol at a stable dose

Exclusion Criteria:

Subject with other types of Antibody Autoimmune Hemolytic Anemia (AIHA) (e.g., cold antibody AIHA, cold agglutinin syndrome, mixed type AIHA, or paroxysmal cold hemoglobinuria).
Subject has AIHA secondary to autoimmune disease, including systemic lupus erythematosus (SLE), or lymphoid malignancy if the underlying disease is not stable or is not well-controlled on current therapy, per investigator medical judgement.
Subject has uncontrolled or poorly controlled hypertension, defined as systolic blood pressure ≥135 mmHg or diastolic blood pressure ≥85 mmHg, whether or not the subject is receiving anti-hypertensive treatment.
Subject has one or more of the following laboratory abnormalities at screening: neutrophil count of <1,000/μL or platelet count of <30,000/μL, unless due to Evans syndrome; transaminase levels (i.e., alanine aminotransferase [ALT] or aspartate aminotransferase [AST]) >1.5 x ULN.
Has documented active hepatitis B or hepatitis C infection or HIV infection.

Facility	Status	City	State	ZIP	Country	Contacts
Banner MD Anderson Cancer Center		Gilbert	Arizona	85234	United States
Mayo Clinic Hospital

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Fostamatinib	Initial dose is 100 mg by mouth (PO) twice a day (bid). At week 4 dose will be increased to fostamatinib 150 mg PO bid if subjects have adequately tolerated the study drug in the opinion of the Investigator. Fostamatinib disodium: Fostamatinib (100mg PO bid or 150 mg PO bid) The dose may be reduced at any time to a dose as low as fostamatinib 100 mg PO once a day (qd) or matching placebo if dose limiting adverse events are observed.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Feb 4, 2022

Arm/Group Information

ID	Title	Description
BG000	Fostamatinib	Initial dose is 100 mg by mouth (PO) twice a day (bid). At week 4 dose will be increased to fostamatinib 150 mg PO bid if subjects have adequately tolerated the study drug in the opinion of the Investigator. Fostamatinib disodium: Fostamatinib (100mg PO bid or 150 mg PO bid) The dose may be reduced at any time to a dose as low as fostamatinib 100 mg PO once a day (qd) or matching placebo if dose limiting adverse events are observed.
BG001	Placebo	Initial dose is 100 mg by mouth (PO) twice a day (bid). At week 4 dose will be increased to placebo 150 mg PO bid if subjects have adequately tolerated the study drug in the opinion of the Investigator. Placebo: Placebo
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Age (years) at Screening

Mean

Standard Deviation

Years

Title

Denominators

Categories

Title	Measurements
	BG00056.8± 15.32 BG00159.9± 15.70 BG00258.4± 15.50

Age, Customized

Count of Participants

Participants

Title

Denominators

Categories

< 65 years

Title	Measurements
	BG00029 BG00123 BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00028 BG00127 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG0002 BG0013 BG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title

Denominators

Categories

White

Title	Measurements
	BG00038 BG00143 BG002

Region of Enrollment

Count of Participants

Participants

Title

Denominators

Categories

United States

Title	Measurements
	BG0009 BG0019 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Durable Hemoglobin Response

Proportion of subjects achieving a hemoglobin level ≥ 10 g/dL with an increase from Baseline in hemoglobin level of ≥ 2 g/dL on 3 consecutive available visits during the 24-week treatment period.

Posted

Count of Participants

Participants

24 Weeks

ID	Title	Description
OG000	Fostamatinib	Initial dose is 100 mg PO bid. At week 4 dose will be increased to fostamatinib 150 mg PO bid if subjects have adequately tolerated the study drug in the opinion of the Investigator. Fostamatinib disodium: Fostamatinib (100mg PO bid or 150 mg PO bid) The dose may be reduced at any time to a dose as low as fostamatinib 100 mg PO qd or matching placebo if dose limiting adverse events are observed.
OG001	Placebo	Initial dose is 100 mg PO bid. At week 4 dose will be increased to placebo 150 mg PO bid if subjects have adequately tolerated the study drug in the opinion of the Investigator. Placebo: Placebo

Units	Counts
Participants	OG00045 OG00145

Title

Denominators

Categories

Title	Measurements
	OG00016 OG00112

Secondary

A Hemoglobin Response by Week 24

Proportion of subjects with a hemoglobin response by Week 24.

Posted

Count of Participants

Participants

24 weeks

ID	Title	Description
OG000	Fostamatinib	Initial dose is 100 mg PO bid. At week 4 dose will be increased to fostamatinib 150 mg PO bid if subjects have adequately tolerated the study drug in the opinion of the Investigator. Fostamatinib disodium: Fostamatinib (100mg PO bid or 150 mg PO bid) The dose may be reduced at any time to a dose as low as fostamatinib 100 mg PO qd or matching placebo if dose limiting adverse events are observed.
OG001	Placebo	Initial dose is 100 mg PO bid. At week 4 dose will be increased to placebo 150 mg PO bid if subjects have adequately tolerated the study drug in the opinion of the Investigator. Placebo: Placebo

Units	Counts
Participants	OG000

Secondary

Change From Baseline in Hemoglobin Level of 2 g/dL or Greater

Proportion of subjects with change from baseline in hemoglobin level of 2 g/dL or greater.

Posted

Count of Participants

Participants

24 weeks

ID	Title	Description
OG000	Fostamatinib	Initial dose is 100 mg PO bid. At week 4 dose will be increased to fostamatinib 150 mg PO bid if subjects have adequately tolerated the study drug in the opinion of the Investigator. Fostamatinib disodium: Fostamatinib (100mg PO bid or 150 mg PO bid) The dose may be reduced at any time to a dose as low as fostamatinib 100 mg PO qd or matching placebo if dose limiting adverse events are observed.
OG001	Placebo	Initial dose is 100 mg PO bid. At week 4 dose will be increased to placebo 150 mg PO bid if subjects have adequately tolerated the study drug in the opinion of the Investigator. Placebo: Placebo

Units	Counts
Participants	OG000

Secondary

Change in Hemoglobin From Baseline to End of Treatment

Change in mean hemoglobin from baseline to end of treatment.

Of the 72 completed participants, 11 participants were excluded due to hemoglobin value missing or not being eligible during the evaluation period.

Posted

Mean

Standard Deviation

g/dL

24 weeks

ID	Title	Description
OG000	Fostamatinib	Initial dose is 100 mg PO bid. At week 4 dose will be increased to fostamatinib 150 mg PO bid if subjects have adequately tolerated the study drug in the opinion of the Investigator. Fostamatinib disodium: Fostamatinib (100mg PO bid or 150 mg PO bid) The dose may be reduced at any time to a dose as low as fostamatinib 100 mg PO qd or matching placebo if dose limiting adverse events are observed.
OG001	Placebo	Initial dose is 100 mg PO bid. At week 4 dose will be increased to placebo 150 mg PO bid if subjects have adequately tolerated the study drug in the opinion of the Investigator. Placebo: Placebo

Units	Counts
Participants

Secondary

Use of Rescue Antibody Autoimmune Hemolytic Anemia (AIHA) Regimens Use After Week 4

Proportion of subjects free of rescue AIHA regimens used after Week 4.

Posted

Count of Participants

Participants

24 weeks

ID	Title	Description
OG000	Fostamatinib	Initial dose is 100 mg PO bid. At week 4 dose will be increased to fostamatinib 150 mg PO bid if subjects have adequately tolerated the study drug in the opinion of the Investigator. Fostamatinib disodium: Fostamatinib (100mg PO bid or 150 mg PO bid) The dose may be reduced at any time to a dose as low as fostamatinib 100 mg PO qd or matching placebo if dose limiting adverse events are observed.
OG001	Placebo	Initial dose is 100 mg PO bid. At week 4 dose will be increased to placebo 150 mg PO bid if subjects have adequately tolerated the study drug in the opinion of the Investigator. Placebo: Placebo

Units	Counts
Participants	OG000

Secondary

Change in Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT-F)

Change from Baseline to Week 24 in Functional Assessment of Chronic Illness Therapy - Fatigue scale (FACIT-F). The FACIT-F scale is a short, 13-item, easy to administer tool that measures an individual's level of fatigue during their usual daily activities over the past week. Each item is rated using a 5-point Likert-type scale. The scale range is 0 to 52, with 0 being the worst possible score and 52 being the best possible score indicating no fatigue. Total Score = [Sum of item scores] x [N of items in subscale] ÷ [N of items answered].

The analysis population includes the intent-to-treat (ITT) population.

Posted

Mean

Standard Deviation

score on a scale

24 weeks

ID	Title	Description
OG000	Fostamatinib	Initial dose is 100 mg PO bid. At week 4 dose will be increased to fostamatinib 150 mg PO bid if subjects have adequately tolerated the study drug in the opinion of the Investigator. Fostamatinib disodium: Fostamatinib (100mg PO bid or 150 mg PO bid) The dose may be reduced at any time to a dose as low as fostamatinib 100 mg PO qd or matching placebo if dose limiting adverse events are observed.
OG001	Placebo	Initial dose is 100 mg PO bid. At week 4 dose will be increased to placebo 150 mg PO bid if subjects have adequately tolerated the study drug in the opinion of the Investigator. Placebo: Placebo

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Fostamatinib	Initial dose is 100 mg PO bid. At week 4 dose will be increased to fostamatinib 150 mg PO bid if subjects have adequately tolerated the study drug in the opinion of the Investigator. Fostamatinib disodium: Fostamatinib (100mg PO bid or 150 mg PO bid) The dose may be reduced at any time to a dose as low as fostamatinib 100 mg PO qd or matching placebo if dose limiting adverse events are observed.	2	45	15	45	42	45
EG001	Placebo	Initial dose is 100 mg PO bid. At week 4 dose will be increased to placebo 150 mg PO bid if subjects have adequately tolerated the study drug in the opinion of the Investigator. Placebo: Placebo	3	45	17	45	40	45

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Warm type hemolytic anemia	Blood and lymphatic system disorders	MedDRA (24.1)	Non-systematic Assessment	EG0006 affected45 at risk EG0016 affected45 at risk
Anemia	Blood and lymphatic system disorders	MedDRA (24.1)	Non-systematic Assessment	EG0001 affected45 at risk EG0012 affected45 at risk
Cold type hemolytic anemia	Blood and lymphatic system disorders	MedDRA (24.1)	Non-systematic Assessment	EG0001 affected45 at risk EG0010 affected45 at risk
COVID-19	Infections and infestations	MedDRA (24.1)	Non-systematic Assessment	EG0000 affected45 at risk EG0013 affected45 at risk
COVID-19 pneumonia	Infections and infestations	MedDRA (24.1)	Non-systematic Assessment	EG0001 affected45 at risk EG0011 affected45 at risk
Pneumonia	Infections and infestations	MedDRA (24.1)	Non-systematic Assessment	EG0001 affected45 at risk EG0011 affected45 at risk
Endocarditis bacterial	Infections and infestations	MedDRA (24.1)	Non-systematic Assessment	EG0000 affected45 at risk EG0011 affected45 at risk
Infection	Infections and infestations	MedDRA (24.1)	Non-systematic Assessment	EG0000 affected45 at risk EG0011 affected45 at risk
Lyme disease	Infections and infestations	MedDRA (24.1)	Non-systematic Assessment	EG0001 affected45 at risk EG0010 affected45 at risk
Pneumonia fungal	Infections and infestations	MedDRA (24.1)	Non-systematic Assessment	EG0001 affected45 at risk EG0010 affected45 at risk
Dyspnea	Respiratory, thoracic and mediastinal disorders	MedDRA (24.1)	Non-systematic Assessment	EG0002 affected45 at risk EG0010 affected45 at risk
Atelectasis	Respiratory, thoracic and mediastinal disorders	MedDRA (24.1)	Non-systematic Assessment	EG0001 affected45 at risk EG0010 affected45 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA (24.1)	Non-systematic Assessment	EG0001 affected45 at risk EG0010 affected45 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA (24.1)	Non-systematic Assessment	EG0001 affected45 at risk EG0010 affected45 at risk
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA (24.1)	Non-systematic Assessment	EG0000 affected45 at risk EG0011 affected45 at risk
Cardiac failure	Cardiac disorders	MedDRA (24.1)	Non-systematic Assessment	EG0001 affected45 at risk EG0011 affected45 at risk
Atrial fibrillation	Cardiac disorders	MedDRA (24.1)	Non-systematic Assessment	EG0001 affected45 at risk EG0010 affected45 at risk
Alanine aminotransferase increased	Investigations	MedDRA (24.1)	Non-systematic Assessment	EG0001 affected45 at risk EG0010 affected45 at risk
Hemoglobin decreased	Investigations	MedDRA (24.1)	Non-systematic Assessment	EG0001 affected45 at risk EG0010 affected45 at risk
Liver function test increased	Investigations	MedDRA (24.1)	Non-systematic Assessment	EG0000 affected45 at risk EG0011 affected45 at risk
Transaminases increased	Investigations	MedDRA (24.1)	Non-systematic Assessment	EG0001 affected45 at risk EG0010 affected45 at risk
Diarrhea	Gastrointestinal disorders	MedDRA (24.1)	Non-systematic Assessment	EG0001 affected45 at risk EG0010 affected45 at risk
Upper gastrointestinal hemorrhage	Gastrointestinal disorders	MedDRA (24.1)	Non-systematic Assessment	EG0000 affected45 at risk EG0011 affected45 at risk
Death	General disorders	MedDRA (24.1)	Non-systematic Assessment	EG0000 affected45 at risk EG0011 affected45 at risk
Multiple organ dysfunction syndrome	General disorders	MedDRA (24.1)	Non-systematic Assessment	EG0001 affected45 at risk EG0010 affected45 at risk
Cholecystitis acute	Hepatobiliary disorders	MedDRA (24.1)	Non-systematic Assessment	EG0000 affected45 at risk EG0011 affected45 at risk
Jaundice	Hepatobiliary disorders	MedDRA (24.1)	Non-systematic Assessment	EG0000 affected45 at risk EG0011 affected45 at risk
Primary biliary cholangitis	Hepatobiliary disorders	MedDRA (24.1)	Non-systematic Assessment	EG0001 affected45 at risk EG0010 affected45 at risk
Foot fracture	Injury, poisoning and procedural complications	MedDRA (24.1)	Non-systematic Assessment	EG0001 affected45 at risk EG0010 affected45 at risk
Spinal compression fracture	Injury, poisoning and procedural complications	MedDRA (24.1)	Non-systematic Assessment	EG0000 affected45 at risk EG0011 affected45 at risk
Hypertension	Vascular disorders	MedDRA (24.1)	Non-systematic Assessment	EG0001 affected45 at risk EG0010 affected45 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Warm type hemolytic anemia	Blood and lymphatic system disorders	MedDRA (24.1)	Non-systematic Assessment	EG00016 affected45 at risk EG00114 affected45 at risk
Anemia	Blood and lymphatic system disorders	MedDRA (24.1)	Non-systematic Assessment	EG0004 affected45 at risk EG0015 affected45 at risk
Fatigue	General disorders	MedDRA (24.1)	Non-systematic Assessment	EG0007 affected45 at risk EG0015 affected45 at risk
Asthenia	General disorders	MedDRA (24.1)	Non-systematic Assessment	EG0004 affected45 at risk EG0016 affected45 at risk
Pyrexia	General disorders	MedDRA (24.1)	Non-systematic Assessment	EG0006 affected45 at risk EG0013 affected45 at risk
Oedema peripheral	General disorders	MedDRA (24.1)	Non-systematic Assessment	EG0003 affected45 at risk EG0013 affected45 at risk
Hemoglobin decreased	Investigations	MedDRA (24.1)	Non-systematic Assessment	EG0008 affected45 at risk EG0016 affected45 at risk
Blood pressure increased	Investigations	MedDRA (24.1)	Non-systematic Assessment	EG0004 affected45 at risk EG0011 affected45 at risk
COVID-19	Infections and infestations	MedDRA (24.1)	Non-systematic Assessment	EG0005 affected45 at risk EG0015 affected45 at risk
Urinary tract infection	Infections and infestations	MedDRA (24.1)	Non-systematic Assessment	EG0004 affected45 at risk EG0013 affected45 at risk
Diarrhea	Gastrointestinal disorders	MedDRA (24.1)	Non-systematic Assessment	EG00012 affected45 at risk EG0013 affected45 at risk
Nausea	Gastrointestinal disorders	MedDRA (24.1)	Non-systematic Assessment	EG0006 affected45 at risk EG0014 affected45 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (24.1)	Non-systematic Assessment	EG0002 affected45 at risk EG0015 affected45 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (24.1)	Non-systematic Assessment	EG0003 affected45 at risk EG0012 affected45 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA (24.1)	Non-systematic Assessment	EG0003 affected45 at risk EG0012 affected45 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA (24.1)	Non-systematic Assessment	EG0001 affected45 at risk EG0014 affected45 at risk
Hypertension	Vascular disorders	MedDRA (24.1)	Non-systematic Assessment	EG00011 affected45 at risk EG0018 affected45 at risk
Dizziness	Nervous system disorders	MedDRA (24.1)	Non-systematic Assessment	EG0002 affected45 at risk EG0015 affected45 at risk
Headache	Nervous system disorders	MedDRA (24.1)	Non-systematic Assessment	EG0003 affected45 at risk EG0014 affected45 at risk
Dyspnea	Respiratory, thoracic and mediastinal disorders	MedDRA (24.1)	Non-systematic Assessment	EG0006 affected45 at risk EG0015 affected45 at risk
Jaundice	Hepatobiliary disorders	MedDRA (24.1)	Non-systematic Assessment	EG0000 affected45 at risk EG0017 affected45 at risk
Alanine aminotransferase increased	Investigations	MedDRA (24.1)	Non-systematic Assessment	EG0003 affected45 at risk EG0011 affected45 at risk
Blood bilirubin increased	Investigations	MedDRA (24.1)	Non-systematic Assessment	EG0001 affected45 at risk EG0013 affected45 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA (24.1)	Non-systematic Assessment	EG0001 affected45 at risk EG0013 affected45 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA (24.1)	Non-systematic Assessment	EG0003 affected45 at risk EG0010 affected45 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (24.1)	Non-systematic Assessment	EG0003 affected45 at risk EG0011 affected45 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA (24.1)	Non-systematic Assessment	EG0001 affected45 at risk EG0013 affected45 at risk
Palpitations	Cardiac disorders	MedDRA (24.1)	Non-systematic Assessment	EG0003 affected45 at risk EG0011 affected45 at risk
Anxiety	Psychiatric disorders	MedDRA (24.1)	Non-systematic Assessment	EG0001 affected45 at risk EG0013 affected45 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA (24.1)	Non-systematic Assessment	EG0003 affected45 at risk EG0010 affected45 at risk