ASPEN: Study of Roxadustat Conversion in Participants Receiving Stable ESA or as Initial Anemia Treatment in Hemodialysis Participants

• Sponsor: FibroGen (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04484857
• Collaborator: AstraZeneca (Industry)
• Enrollment: 283
• Locations: 26
• Arm: 1
• Actual Duration (Months): 13.9
• Patients Per Site: 10.9
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the safety and effectiveness of roxadustat dosing regimens among hemodialysis participants converted from erythropoiesis stimulating agent (ESA) therapy or who are ESA-naïve.

Condition or Disease	Intervention/Treatment	Phase
Anemia Associated With End Stage Renal Disease	Drug: Roxadustat	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 283 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase 3b Multicenter, Open-Label Single Arm Study of Roxadustat: Either as Conversion From an Erythropoiesis Stimulating Agent (ESA), or as Initial Anemia Treatment in Hemodialysis (HD) Patients
• Actual Study Start Date: Jul 22, 2020
• Actual Primary Completion Date: Jul 9, 2021
• Actual Study Completion Date: Sep 17, 2021

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Roxadustat Participants will receive roxadustat as an oral tablet, 3 times per week (TIW) for up to a maximum of 24 weeks. If a participant require roxadustat <60 milligrams (mg)/week to maintain hemoglobin (Hb) levels, the dose frequency will be reduced in a stepwise manner, for example, to twice weekly (BIW), and then once weekly (QW). For participants converted from an ESA, the initial roxadustat dose will be based on the average prescribed ESA dose in the last 4 weeks (for epoetin alfa and darbepoetin alfa) or 8 weeks (for methoxy polyethylene glycol-epoetin beta [Mircera®]). For participants with <6 weeks of prior ESA use, the initial roxadustat dose will be based on a 2-tiered, weight-based dosing scheme. Dose adjustment evaluations will be made every 4 weeks and doses will be titrated based on Hb level and rate of Hb change. The prescribed dose will not exceed the maximum allowable dose of 3.0 mg/kilogram (kg)/dose or 400 mg per dose, whichever is lower.

Drug: Roxadustat; Roxadustat will be administered per dose and schedule specified in the arm description.

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Mean Hb Value ≥10 g/dL [Week 16 through Week 24]

   Percentage of participants with mean Hb value ≥10 g/dL, averaged from Week 16 through Week 24 has been reported. Baseline Hb was defined as the mean of available central laboratory Hb values prior to first dose of study medication including the predose Hb value collected on Day 1. 95% confidence interval (CI) was calculated based on the normal approximation to the binomial distribution.

2. Mean Hb Change From Baseline to Average Hb From Weeks 16-24 [Baseline, Weeks 16-24]

   Baseline Hb was defined as the mean of available central laboratory Hb values prior to first dose of study medication including the predose Hb value collected on Day 1. Missing data was imputed using Monte Carlo Markov Chain (MCMC) imputation model.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Key Inclusion Criteria:

• Receiving chronic dialysis for end stage renal disease (ESRD)

• Vascular access must be a functioning native arteriovenous fistula or graft with adequate flow in the opinion of the investigator, or permanent tunnelled catheter

• Screening Hb criteria: Participants converting from an ESA: between 9.0 to 12.0 grams (g)/deciliter (dL); Participants initiating anemia treatment: < 10.0 g/dL

• Ferritin ≥ 50 nanograms (ng)/mililiter (mL), Transferrin saturation (TSAT) ≥ 10% at screening

• Participant's alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are ≤ 3 x upper limit of normal (ULN), and total bilirubin (TBL) is ≤ 1.5 x ULN at screening and prior to initiating roxadustat treatment.

• Body weight between 45.0 to 160.0 kg

Key Exclusion Criteria:

• Red blood cell (RBC) transfusion within 4 weeks prior to enrollment

• Known history of myelodysplastic syndrome or multiple myeloma

• Known hereditary hematologic disease or other known causes for anemia other than chronic kidney disease (CKD)

• Known chronic inflammatory disease that is determined by the investigator to be the primary cause of anemia

• Active or chronic gastrointestinal bleeding

• Treated with iron-chelating agents within 4 weeks prior to enrollment

• History of New York Heart Association (NYHA) Class III or IV congestive heart failure

• History of myocardial infarction, acute coronary syndrome, stroke, seizure, or a thrombotic/thromboembolic event (excluding vascular dialysis access stenosis/thrombosis) within 12 weeks prior to enrollment

• Uncontrolled hypertension, in the opinion of the Investigator

• Participant has a diagnosis or suspicion (for example, complex kidney cyst of Bosniak Category II or higher) of renal cell carcinoma (Principal Investigator's discretion)

• History of malignancy, except for cancers determined to be cured or in remission for ≥ 2 years, curatively resected basal cell or squamous cell skin cancers, cervical cancer in situ, or resected colonic polyps

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Alaska	Anchorage	Alaska	United States	99515
2	Investigator Site	Pine Bluff	Arkansas	United States	71603
3	Investigational Site	Cerritos	California	United States	90703
4	Investigational Site	Victorville	California	United States	92394
5	Investigational Site	Denver	Colorado	United States	80230
6	Investigational Site	Hartford	Connecticut	United States	06112
7	Investigational Site	Coral Gables	Florida	United States	33134
8	Investigational Site	Hollywood	Florida	United States	33024
9	Investigator Site	Dalton	Georgia	United States	30720
10	Investigational Site	Statesboro	Georgia	United States	30458
11	Investigational Site	Roseville	Michigan	United States	48066
12	Investigational Site	Kansas City	Missouri	United States	64111
13	Investigational Site	Las Vegas	Nevada	United States	89178
14	Investigator Site	Gallup	New Mexico	United States	87301
15	Investigational Site	Bronx	New York	United States	10461
16	Investigational Site	Austin	Texas	United States	78229
17	Investigator Site	Dallas	Texas	United States	75237
18	Investigational Site	El Paso	Texas	United States	79924
19	Investigational Site	Houston	Texas	United States	77004
20	Investigator Site	San Antonio	Texas	United States	78202
21	Investigator Site	San Antonio	Texas	United States	78211
22	Investigator Site	San Antonio	Texas	United States	78221
23	Investigational Site	San Antonio	Texas	United States	78229
24	Investigational Site	San Antonio	Texas	United States	78251
25	Investigator Sites	San Antonio	Texas	United States	78521
26	Investigational Site	Norfolk	Virginia	United States	23502

Sponsors and Collaborators

• FibroGen
• AstraZeneca

Investigators

• Study Chair: Mark Eisner, FibroGen

Study Documents (Full-Text)

• Study Protocol - Aug 20, 2020
• Statistical Analysis Plan - Sep 9, 2021

More Information

Publications

None provided.

• Responsible Party: FibroGen
• ClinicalTrials.gov Identifier: NCT04484857
• Other Study ID Numbers: FGCL-4592-096
• First Posted: Jul 24, 2020
• Last Update Posted: Jul 26, 2022
• Last Verified: Jun 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Kidney Failure, Chronic; Anemia

Study Results

Participant Flow

Arm/Group Title	Roxadustat
Arm/Group Description	Participants received roxadustat as an oral tablet, 3 times per week (TIW) for up to a maximum of 24 weeks. If a participant required roxadustat <60 milligrams (mg)/week to maintain hemoglobin (Hb) levels, the dose frequency was reduced in a stepwise manner, for example, to twice weekly (BIW), and then once weekly (QW). For participants converted from an erythropoiesis stimulating agent (ESA), the initial roxadustat dose was based on the average prescribed ESA dose in the last 4 weeks (for epoetin alfa and darbepoetin alfa) or 8 weeks (for methoxy polyethylene glycol-epoetin beta [Mircera®]). For participants with <6 weeks of prior ESA use, the initial roxadustat dose was based on a 2-tiered, weight-based dosing scheme. Dose adjustment evaluations were made every 4 weeks and doses were titrated based on Hb level and rate of Hb change. The prescribed dose did not exceed the maximum allowable dose of 3.0 mg/kilogram (kg)/dose or 400 mg per dose, whichever was lower.
Period Title: Overall Study
STARTED	283
Received at Least 1 Dose of Study Drug	283
Full Analysis Set	282
COMPLETED	36
NOT COMPLETED	247

Baseline Characteristics

Arm/Group Title	Roxadustat
Arm/Group Description	Participants received roxadustat as an oral tablet, TIW for up to a maximum of 24 weeks. If a participant required roxadustat <60 mg/week to maintain Hb levels, the dose frequency was reduced in a stepwise manner, for example, to BIW, and then QW. For participants converted from an ESA, the initial roxadustat dose was based on the average prescribed ESA dose in the last 4 weeks (for epoetin alfa and darbepoetin alfa) or 8 weeks (for Mircera®). For participants with <6 weeks of prior ESA use, the initial roxadustat dose was based on a 2-tiered, weight-based dosing scheme. Dose adjustment evaluations were made every 4 weeks and doses were titrated based on Hb level and rate of Hb change. The prescribed dose did not exceed the maximum allowable dose of 3.0 mg/kg/dose or 400 mg per dose, whichever was lower.
Overall Participants	283
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59.0 (13.12)
Sex: Female, Male (Count of Participants)
Female	116 41%
Male	167 59%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	91 32.2%
Not Hispanic or Latino	191 67.5%
Unknown or Not Reported	1 0.4%
Race/Ethnicity, Customized (Count of Participants)
Black or African American	113 39.9%
American Indian or Alaska Native	17 6%
Asian	8 2.8%
Native Hawaiian or Other Pacific Islander	5 1.8%
White	131 46.3%
Other	7 2.5%
Not Reported	2 0.7%
Baseline Hb (grams (g)/deciliter (dL)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [grams (g)/deciliter (dL)]	10.554 (0.7228)

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Mean Hb Value ≥10 g/dL
Description	Percentage of participants with mean Hb value ≥10 g/dL, averaged from Week 16 through Week 24 has been reported. Baseline Hb was defined as the mean of available central laboratory Hb values prior to first dose of study medication including the predose Hb value collected on Day 1. 95% confidence interval (CI) was calculated based on the normal approximation to the binomial distribution.
Time Frame	Week 16 through Week 24

Outcome Measure Data

Analysis Population Description

The full analysis set included all enrolled participants who provided baseline Hb data and data for at least 1 postbaseline Hb time point.

Arm/Group Title	Roxadustat
Arm/Group Description	Participants received roxadustat as an oral tablet, TIW for up to a maximum of 24 weeks. If a participant required roxadustat <60 mg/week to maintain Hb levels, the dose frequency was reduced in a stepwise manner, for example, to BIW, and then QW. For participants converted from an ESA, the initial roxadustat dose was based on the average prescribed ESA dose in the last 4 weeks (for epoetin alfa and darbepoetin alfa) or 8 weeks (for Mircera®). For participants with <6 weeks of prior ESA use, the initial roxadustat dose was based on a 2-tiered, weight-based dosing scheme. Dose adjustment evaluations were made every 4 weeks and doses were titrated based on Hb level and rate of Hb change. The prescribed dose did not exceed the maximum allowable dose of 3.0 mg/kg/dose or 400 mg per dose, whichever was lower.
Measure Participants	282
Number (95% Confidence Interval) [percentage of participants]	83.7 29.6%

2. Primary Outcome

Title	Mean Hb Change From Baseline to Average Hb From Weeks 16-24
Description	Baseline Hb was defined as the mean of available central laboratory Hb values prior to first dose of study medication including the predose Hb value collected on Day 1. Missing data was imputed using Monte Carlo Markov Chain (MCMC) imputation model.
Time Frame	Baseline, Weeks 16-24

Outcome Measure Data

Analysis Population Description

The full analysis set included all enrolled participants who provided baseline Hb data and data for at least 1 postbaseline Hb time point.

Arm/Group Title	Roxadustat
Arm/Group Description	Participants received roxadustat as an oral tablet, TIW for up to a maximum of 24 weeks. If a participant required roxadustat <60 mg/week to maintain Hb levels, the dose frequency was reduced in a stepwise manner, for example, to BIW, and then QW. For participants converted from an ESA, the initial roxadustat dose was based on the average prescribed ESA dose in the last 4 weeks (for epoetin alfa and darbepoetin alfa) or 8 weeks (for Mircera®). For participants with <6 weeks of prior ESA use, the initial roxadustat dose was based on a 2-tiered, weight-based dosing scheme. Dose adjustment evaluations were made every 4 weeks and doses were titrated based on Hb level and rate of Hb change. The prescribed dose did not exceed the maximum allowable dose of 3.0 mg/kg/dose or 400 mg per dose, whichever was lower.
Measure Participants	282
Mean (Standard Deviation) [g/dL]	0.22 (1.029)

Adverse Events

Time Frame	Baseline up to 28 days post last dose of roxadustat (Week 28)
Adverse Event Reporting Description	The safety analysis set included all enrolled participants who received at least 1 dose of study treatment.
Arm/Group Title	Roxadustat
Arm/Group Description	Participants received roxadustat as an oral tablet, TIW for up to a maximum of 24 weeks. If a participant required roxadustat <60 mg/week to maintain Hb levels, the dose frequency was reduced in a stepwise manner, for example, to BIW, and then QW. For participants converted from an ESA, the initial roxadustat dose was based on the average prescribed ESA dose in the last 4 weeks (for epoetin alfa and darbepoetin alfa) or 8 weeks (for Mircera®). For participants with <6 weeks of prior ESA use, the initial roxadustat dose was based on a 2-tiered, weight-based dosing scheme. Dose adjustment evaluations were made every 4 weeks and doses were titrated based on Hb level and rate of Hb change. The prescribed dose did not exceed the maximum allowable dose of 3.0 mg/kg/dose or 400 mg per dose, whichever was lower.
All Cause Mortality
	Roxadustat
	Affected / at Risk (%)	# Events
Total	11/283 (3.9%)
Serious Adverse Events
	Roxadustat
	Affected / at Risk (%)	# Events
Total	82/283 (29%)
Blood and lymphatic system disorders
Anaemia	1/283 (0.4%)
Cardiac disorders
Acute myocardial infarction	7/283 (2.5%)
Cardiac arrest	5/283 (1.8%)
Cardiac failure congestive	4/283 (1.4%)
Cardiac failure acute	2/283 (0.7%)
Coronary artery disease	2/283 (0.7%)
Angina unstable	1/283 (0.4%)
Atrial fibrillation	1/283 (0.4%)
Atrioventricular block complete	1/283 (0.4%)
Cardiogenic shock	1/283 (0.4%)
Coronary artery stenosis	1/283 (0.4%)
Mitral valve incompetence	1/283 (0.4%)
Myocardial infarction	1/283 (0.4%)
Pulseless electrical activity	1/283 (0.4%)
Eye disorders
Orbital haematoma	1/283 (0.4%)
Gastrointestinal disorders
Upper gastrointestinal haemorrhage	2/283 (0.7%)
Abdominal discomfort	1/283 (0.4%)
Abdominal pain	1/283 (0.4%)
Colitis	1/283 (0.4%)
Duodenitis	1/283 (0.4%)
Gastritis	1/283 (0.4%)
Gastrointestinal haemorrhage	1/283 (0.4%)
Haemorrhoids	1/283 (0.4%)
Nausea	1/283 (0.4%)
Rectal haemorrhage	1/283 (0.4%)
Vomiting	1/283 (0.4%)
General disorders
Non-cardiac chest pain	2/283 (0.7%)
General physical health deterioration	1/283 (0.4%)
Organ failure	1/283 (0.4%)
Treatment noncompliance	1/283 (0.4%)
Hepatobiliary disorders
Haemorrhagic hepatic cyst	1/283 (0.4%)
Non-alcoholic steatohepatitis	1/283 (0.4%)
Infections and infestations
COVID-19 pneumonia	10/283 (3.5%)
COVID-19	7/283 (2.5%)
Pneumonia	5/283 (1.8%)
Urinary tract infection	5/283 (1.8%)
Sepsis	2/283 (0.7%)
Arteriovenous graft site infection	1/283 (0.4%)
Bone abscess	1/283 (0.4%)
Cellulitis	1/283 (0.4%)
Diabetic foot infection	1/283 (0.4%)
Enterobacter sepsis	1/283 (0.4%)
Enterococcal infection	1/283 (0.4%)
Escherichia infection	1/283 (0.4%)
Gangrene	1/283 (0.4%)
Helicobacter infection	1/283 (0.4%)
Herpes zoster	1/283 (0.4%)
Pseudomonal bacteraemia	1/283 (0.4%)
Pyelonephritis	1/283 (0.4%)
Pyelonephritis acute	1/283 (0.4%)
Septic shock	1/283 (0.4%)
Skin infection	1/283 (0.4%)
Injury, poisoning and procedural complications
Fall	3/283 (1.1%)
Arteriovenous fistula site complication	2/283 (0.7%)
Arteriovenous fistula thrombosis	1/283 (0.4%)
Arteriovenous graft site pseudoaneurysm	1/283 (0.4%)
Arteriovenous graft thrombosis	1/283 (0.4%)
Concussion	1/283 (0.4%)
Postoperative respiratory failure	1/283 (0.4%)
Skin laceration	1/283 (0.4%)
Toxicity to various agents	1/283 (0.4%)
Upper limb fracture	1/283 (0.4%)
Vascular access site pain	1/283 (0.4%)
Metabolism and nutrition disorders
Fluid overload	6/283 (2.1%)
Hyperkalaemia	3/283 (1.1%)
Hypoglycaemia	2/283 (0.7%)
Hypervolaemia	1/283 (0.4%)
Musculoskeletal and connective tissue disorders
Cervical spinal stenosis	1/283 (0.4%)
Pain in extremityvvv	1/283 (0.4%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Non-small cell lung cancer	1/283 (0.4%)
Nervous system disorders
Cerebrovascular accident	2/283 (0.7%)
Basal ganglia haemorrhage	1/283 (0.4%)
Dysarthria	1/283 (0.4%)
Encephalopathy	1/283 (0.4%)
Ischaemic stroke	1/283 (0.4%)
Syncope	1/283 (0.4%)
Psychiatric disorders
Confusional state	1/283 (0.4%)
Mental status changes	1/283 (0.4%)
Renal and urinary disorders
Azotaemia	1/283 (0.4%)
Hydroureter	1/283 (0.4%)
Reproductive system and breast disorders
Scrotal swelling	1/283 (0.4%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	9/283 (3.2%)
Dyspnoea	5/283 (1.8%)
Pleural effusion	4/283 (1.4%)
Respiratory failure	3/283 (1.1%)
Pulmonary oedema	2/283 (0.7%)
Acute pulmonary oedema	1/283 (0.4%)
Chronic obstructive pulmonary disease	1/283 (0.4%)
Hypoxia	1/283 (0.4%)
Pulmonary embolism	1/283 (0.4%)
Skin and subcutaneous tissue disorders
Diabetic foot	1/283 (0.4%)
Skin ulcer	1/283 (0.4%)
Surgical and medical procedures
Hip arthroplasty	1/283 (0.4%)
Vascular disorders
Hypotension	5/283 (1.8%)
Hypertensive emergency	4/283 (1.4%)
Hypertensive urgency	3/283 (1.1%)
Hypertension	2/283 (0.7%)
Deep vein thrombosis	1/283 (0.4%)
Embolism	1/283 (0.4%)
Peripheral vascular disorder	1/283 (0.4%)
Other (Not Including Serious) Adverse Events
	Roxadustat
	Affected / at Risk (%)	# Events
Total	19/283 (6.7%)
Infections and infestations
COVID-19	19/283 (6.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The multisite consortium can publish any time after the data is collected and analyzed by FibroGen. The investigator can only publish after the multisite consortium publishes (or tries to publish and fails). FibroGen has 60 days to review a publication and can extend the embargo up to an additional 120 days (or 180 total).