Trial Outcomes & Findings for A Phase 3, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Study of Fostamatinib Disodium in the Treatment of wAIHA (NCT NCT03764618)

Last Updated: 2023-05-25

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

90 participants

Primary outcome timeframe

24 Weeks

Results posted on

2023-05-25

Participant Flow

Participant milestones

Participant milestones
Measure	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.	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
Overall Study STARTED	45	45
Overall Study COMPLETED	38	34
Overall Study NOT COMPLETED	7	11

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Phase 3, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Study of Fostamatinib Disodium in the Treatment of wAIHA

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Fostamatinib n=45 Participants 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.	Placebo n=45 Participants 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	Total n=90 Participants Total of all reporting groups
Age, Continuous	56.8 Years STANDARD_DEVIATION 15.32 • n=5 Participants	59.9 Years STANDARD_DEVIATION 15.70 • n=7 Participants	58.4 Years STANDARD_DEVIATION 15.50 • n=5 Participants
Age, Customized < 65 years	29 Participants n=5 Participants	23 Participants n=7 Participants	52 Participants n=5 Participants
Age, Customized ≥ 65 years	16 Participants n=5 Participants	22 Participants n=7 Participants	38 Participants n=5 Participants
Sex: Female, Male Female	28 Participants n=5 Participants	27 Participants n=7 Participants	55 Participants n=5 Participants
Sex: Female, Male Male	17 Participants n=5 Participants	18 Participants n=7 Participants	35 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	40 Participants n=5 Participants	40 Participants n=7 Participants	80 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Race/Ethnicity, Customized White	38 Participants n=5 Participants	43 Participants n=7 Participants	81 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Asian	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Missing	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Region of Enrollment United States	9 Participants n=5 Participants	9 Participants n=7 Participants	18 Participants n=5 Participants
Region of Enrollment Czechia	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Region of Enrollment Ukraine	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Region of Enrollment United Kingdom	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment Belarus	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment Russia	5 Participants n=5 Participants	0 Participants n=7 Participants	5 Participants n=5 Participants
Region of Enrollment Spain	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Region of Enrollment Canada	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment Austria	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants
Region of Enrollment Netherlands	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment Belgium	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment Norway	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment Italy	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Region of Enrollment Georgia	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Region of Enrollment Australia	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Region of Enrollment Bulgaria	5 Participants n=5 Participants	10 Participants n=7 Participants	15 Participants n=5 Participants
Region of Enrollment France	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Region of Enrollment Serbia	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment Germany	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants

PRIMARY outcome

Timeframe: 24 Weeks

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.

Outcome measures

Outcome measures
Measure	Fostamatinib n=45 Participants 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.	Placebo n=45 Participants 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
Durable Hemoglobin Response	16 Participants	12 Participants

SECONDARY outcome

Timeframe: 24 weeks

Proportion of subjects with a hemoglobin response by Week 24.

Outcome measures

Outcome measures
Measure	Fostamatinib n=45 Participants 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.	Placebo n=45 Participants 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
A Hemoglobin Response by Week 24	21 Participants	16 Participants

SECONDARY outcome

Timeframe: 24 weeks

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

Outcome measures

Outcome measures
Measure	Fostamatinib n=45 Participants 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.	Placebo n=45 Participants 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
Change From Baseline in Hemoglobin Level of 2 g/dL or Greater	22 Participants	16 Participants

SECONDARY outcome

Timeframe: 24 weeks

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

Change in mean hemoglobin from baseline to end of treatment.

Outcome measures

Outcome measures
Measure	Fostamatinib n=32 Participants 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.	Placebo n=29 Participants 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
Change in Hemoglobin From Baseline to End of Treatment	1.99 g/dL Standard Deviation 2.095	1.99 g/dL Standard Deviation 2.468

SECONDARY outcome

Timeframe: 24 weeks

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

Outcome measures

Outcome measures
Measure	Fostamatinib n=45 Participants 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.	Placebo n=45 Participants 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
Use of Rescue Antibody Autoimmune Hemolytic Anemia (AIHA) Regimens Use After Week 4	18 Participants	18 Participants

SECONDARY outcome

Timeframe: 24 weeks

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

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 \[N of items in subscale\] ÷ \[N of items answered\].

Outcome measures

Outcome measures
Measure	Fostamatinib n=39 Participants 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.	Placebo n=37 Participants 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
Change in Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT-F)	4.1 score on a scale Standard Deviation 12.86	2.2 score on a scale Standard Deviation 11.03

Adverse Events

Fostamatinib

Serious events: 15 serious events

Other events: 42 other events

Deaths: 2 deaths

Placebo

Serious events: 17 serious events

Other events: 40 other events

Deaths: 3 deaths

Serious adverse events

Other adverse events

Additional Information

Executive Director, Global Clinical Operations

Rigel Pharmaceuticals, Inc.

Phone: (650) 624-1100

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Fostamatinib n=45 participants at risk 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.	Placebo n=45 participants at risk 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
Blood and lymphatic system disorders Warm type hemolytic anemia	13.3% 6/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)	13.3% 6/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)
Blood and lymphatic system disorders Anemia	2.2% 1/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)	4.4% 2/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)
Blood and lymphatic system disorders Cold type hemolytic anemia	2.2% 1/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)	0.00% 0/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)
Infections and infestations COVID-19	0.00% 0/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)	6.7% 3/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)
Infections and infestations COVID-19 pneumonia	2.2% 1/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)	2.2% 1/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)
Infections and infestations Pneumonia	2.2% 1/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)	2.2% 1/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)
Infections and infestations Endocarditis bacterial	0.00% 0/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)	2.2% 1/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)
Infections and infestations Infection	0.00% 0/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)	2.2% 1/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)
Infections and infestations Lyme disease	2.2% 1/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)	0.00% 0/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)
Infections and infestations Pneumonia fungal	2.2% 1/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)	0.00% 0/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)
Respiratory, thoracic and mediastinal disorders Dyspnea	4.4% 2/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)	0.00% 0/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)
Respiratory, thoracic and mediastinal disorders Atelectasis	2.2% 1/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)	0.00% 0/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)
Respiratory, thoracic and mediastinal disorders Pleural effusion	2.2% 1/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)	0.00% 0/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	2.2% 1/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)	0.00% 0/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.00% 0/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)	2.2% 1/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)
Cardiac disorders Cardiac failure	2.2% 1/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)	2.2% 1/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)
Cardiac disorders Atrial fibrillation	2.2% 1/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)	0.00% 0/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)
Investigations Alanine aminotransferase increased	2.2% 1/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)	0.00% 0/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)
Investigations Hemoglobin decreased	2.2% 1/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)	0.00% 0/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)
Investigations Liver function test increased	0.00% 0/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)	2.2% 1/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)
Investigations Transaminases increased	2.2% 1/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)	0.00% 0/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)
Gastrointestinal disorders Diarrhea	2.2% 1/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)	0.00% 0/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)
Gastrointestinal disorders Upper gastrointestinal hemorrhage	0.00% 0/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)	2.2% 1/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)
General disorders Death	0.00% 0/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)	2.2% 1/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)
General disorders Multiple organ dysfunction syndrome	2.2% 1/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)	0.00% 0/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)
Hepatobiliary disorders Cholecystitis acute	0.00% 0/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)	2.2% 1/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)
Hepatobiliary disorders Jaundice	0.00% 0/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)	2.2% 1/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)
Hepatobiliary disorders Primary biliary cholangitis	2.2% 1/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)	0.00% 0/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)
Injury, poisoning and procedural complications Foot fracture	2.2% 1/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)	0.00% 0/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)
Injury, poisoning and procedural complications Spinal compression fracture	0.00% 0/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)	2.2% 1/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)
Vascular disorders Hypertension	2.2% 1/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)	0.00% 0/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)

Measure	Fostamatinib n=45 participants at risk 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.	Placebo n=45 participants at risk 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
General disorders Fatigue	15.6% 7/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)	11.1% 5/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)
General disorders Asthenia	8.9% 4/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)	13.3% 6/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)
General disorders Pyrexia	13.3% 6/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)	6.7% 3/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)
General disorders Oedema peripheral	6.7% 3/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)	6.7% 3/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)
Investigations Hemoglobin decreased	17.8% 8/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)	13.3% 6/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)
Investigations Blood pressure increased	8.9% 4/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)	2.2% 1/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)
Infections and infestations COVID-19	11.1% 5/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)	11.1% 5/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)
Infections and infestations Urinary tract infection	8.9% 4/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)	6.7% 3/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)
Gastrointestinal disorders Diarrhea	26.7% 12/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)	6.7% 3/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)
Gastrointestinal disorders Nausea	13.3% 6/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)	8.9% 4/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)
Musculoskeletal and connective tissue disorders Arthralgia	4.4% 2/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)	11.1% 5/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)
Blood and lymphatic system disorders Warm type hemolytic anemia	35.6% 16/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)	31.1% 14/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)
Blood and lymphatic system disorders Anemia	8.9% 4/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)	11.1% 5/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)
Musculoskeletal and connective tissue disorders Back pain	6.7% 3/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)	4.4% 2/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)
Musculoskeletal and connective tissue disorders Muscle spasms	6.7% 3/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)	4.4% 2/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)
Musculoskeletal and connective tissue disorders Pain in extremity	2.2% 1/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)	8.9% 4/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)
Vascular disorders Hypertension	24.4% 11/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)	17.8% 8/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)
Nervous system disorders Dizziness	4.4% 2/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)	11.1% 5/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)
Nervous system disorders Headache	6.7% 3/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)	8.9% 4/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)
Respiratory, thoracic and mediastinal disorders Dyspnea	13.3% 6/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)	11.1% 5/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)
Hepatobiliary disorders Jaundice	0.00% 0/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)	15.6% 7/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)
Investigations Alanine aminotransferase increased	6.7% 3/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)	2.2% 1/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)
Investigations Blood bilirubin increased	2.2% 1/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)	6.7% 3/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)
Gastrointestinal disorders Abdominal pain upper	2.2% 1/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)	6.7% 3/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)
Gastrointestinal disorders Dyspepsia	6.7% 3/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)	0.00% 0/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)
Respiratory, thoracic and mediastinal disorders Cough	6.7% 3/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)	2.2% 1/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)
Metabolism and nutrition disorders Decreased appetite	2.2% 1/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)	6.7% 3/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)
Cardiac disorders Palpitations	6.7% 3/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)	2.2% 1/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)
Psychiatric disorders Anxiety	2.2% 1/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)	6.7% 3/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)
Blood and lymphatic system disorders Neutropenia	6.7% 3/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)	0.00% 0/45 • Up to 30 weeks (-28 days screening, 24 weeks treatment, 2 weeks post treatment follow-up)