A Phase 2A Trial of FMX-8 Treatment for Anemia in Patients With ESRD on Hemodialysis HD

Phase 2

Terminated

Conditions: Anemia of Chronic Disease

Interventions: Drug: FMX-8

Registration Number: NCT01873534

Lead Sponsor: FerruMax Pharmaceuticals, Inc.

Brief Summary: The trial is an uncontrolled, open-label, parallel group clinical trial. Approximately 10 subjects per dose group in 3 groups will be treated twice weekly for a total of 9 doses, followed by a 4-week observation period. Eligible subjects who have Hgb ≥10.5 g/dL and have stable Hgb levels will start the washout period of one to eight weeks. During the washout period, 30 subjects whose Hgb are \< 10.0 will complete the baseline assessment to confirm their eligibility. Eligible subjects will be randomly assigned to one of the 3 cohorts in a 1:1:1 ratio. Subjects will be admitted on the day of the first dose and stay in the clinic overnight for pharmacokinetic (PK) sampling after the first (day 1) and the last dose (day 29). FMX-8 will be administered as 30 min i.v. infusion. After the 29-day treatment period, the trial subjects will be observed for an additional 28 days to allow safety and immunogenicity assessments.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 6

Inclusion Criteria

Male or female patients who are ≥18 years old
Diagnosed with ESRD and are stable on hemodialysis for more than 3 months
Maintained stable Hgb for ≥4 weeks prior to screening
Two consecutive Hgb values ≥10.5 g/dL within 5 weeks of screening
Body mass index (BMI) between 18 kg/m2 and 42 kg/m2, inclusive, based upon the latest height and weight
Ferritin levels ≥100 mg/L or Tsat ≥20% or reticulocyte hemoglobin content (CHr) >25 at screening
Reasonable clearances on dialysis (KT/V ≥1.0) on two prior determinations within 2.5 months
Able to provide written informed consent
Able to understand and follow all trial procedures
Willing to use contraception as detailed in the protocol

Exclusion Criteria

Hgb remains unchanged without erythropoietin (<0.5 g/dL decrease during the 8 week maximum erythropoietin-washout period)
Receipt of iron infusion after the initiation of erythropoietin washout
Receipt of red blood cell transfusion within four weeks before screening
Overt gastrointestinal bleeding or other bleeding episode that required transfusion within 2 months prior to screening
Infection necessitating antibiotic or anti-viral treatment within a month prior to screening
Requirement for Coumadin (warfarin), Pradaxa or Xarelto
Hemoglobinopathies such as homozygous sickle-cell disease or thalassemias of all types
Active hemolysis or chronic hypoxia
Active malignant diseases (except non-melanoma skin cancer) or life expectancy less than 6 months
Chronic, uncontrolled or symptomatic inflammatory disease or non-renal cause of anemia such as rheumatoid arthritis, systemic lupus erythematosus, HIV, or systemic acute infection
On immunosuppressive therapeutics
Chronic congestive heart failure (New York Heart Association Class III, IV)
Significant hypertension (≥90 diastolic) based on a sitting diastolic blood pressure at screening
Kidney transplant within the past year: patients who are off immunosuppressive agents following a failed transplant are eligible for the trial
End-stage liver disease
Known hypersensitivity to recombinant protein therapies
Female patients who are pregnant or breast feeding
Previous exposure to FMX-8
Exposure to Omontys® or Hematide® (peginesatide) anemia treatment within the past 6 months
Treatment with Aranesp® (darbepoetin alpha) within the past 4 weeks
Uncontrolled hyperparathyroidism (PTH >750) based upon latest PTH determination within the past 4 months
Inability to comply with the trial scheduled visits

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
FMX-8 (5 mg/kg)	FMX-8	5 mg/kg FMX-8 IV twice per week for 29 days (9 doses)
FMX-8 (15 mg/kg)	FMX-8	15 mg/kg FMX-8 IV twice per week for 29 days (9 doses)
FMX-8 (0.5 mg/kg)	FMX-8	0.5 mg/kg FMX-8 IV twice per week for 29 days (9 doses)

Primary Outcome Measures

Name	Time	Method
The proportion of subjects who achieve an increase in Hgb ≥ 1g/dL from the lowest Hgb concentration post erythropoietin-washout or continuing rise in Hgb concentration for two consecutive weeks	Weekly for 8 weeks
Number and Severity of Adverse Events	8 weeks
Serum FMX-8 levels	Dosing Days 1 and 29	Serum drug levels (pre-dose, and 25 minutes, 35 minutes, 1, 2, 4, 6, 10, 16 and 24 hrs post-dose) will be used to determine, for each dose, standard pK profiles
Number of Subjects with Positive Serum for Anti-Drug Antibodies	At 36 and 57 days after first dose of FMX-8

Secondary Outcome Measures

Name	Time	Method
Changes in Hgb in each dose group during the treatment and follow-up periods	Weekly for 8 weeks
Proportion of subjects needing erythropoietin rescue and length of time to start of rescue therapy	Weekly for 8 weeks
Change of hepcidin and erythropoietin	At weeks 2, 4, 6 and 8 from baseline
Time to Hgb increase ≥1 g/dL	Weekly for 8 weeks
Proportion of subjects that achieve/maintain an absolute Hgb concentration of ≥ 10.0 g/dL for two consecutive weeks	Weekly for 8 weeks
Time to beginning of steady increase of Hgb (for two consecutive weeks)	Weekly for 8 weeks
Time to full recovery of Hgb to pre- erythropoietin-washout level	Weekly for 8 weeks
Changes in Serum Iron, Tsat and plasma Ferritin	At weeks 2, 4, 6 and 8 compared to baseline

Trial Locations

Locations (2): DaVita Arvada Dialysis Center
🇺🇸
Arvada, Colorado, United States
DaVita Minneapolis Dialysis Unit
🇺🇸
Minneapolis, Minnesota, United States