A Phase 2 Study of Intravenous or Subcutaneous Dosing of Sotatercept (ACE-011) in Patients With End-Stage Kidney Disease on Hemodialysis

Phase 2CompletedNCT01999582

Celgene50 enrolled

Overview

To determine the optimal route of administration, dose level, and safety of intravenous and subcutaneous dosing of sotatercept for maintaining hemoglobin levels in subjects who are on hemodialysis.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Anemia Kidney Failure, Chronic

Interventions

SotaterceptBIOLOGICAL

Sotatercept is dosed intravenously every 14 days. The dose a subject receives will depend on the randomization arm and the dose group.

SotaterceptBIOLOGICAL

Sotatercept is dosed subcutaneously every 14 days. The dose a subject receives will depend on the randomization arm and the dose group.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Males or females ≥ 18 years of age. 2. Subjects on at least 6 hours of hemodialysis per week, for at least 12 weeks before screening 3. Subjects must be on a stable intravenous or subcutaneous dose of Erythropoietin Stimulating Agents (excluding methoxy polyethylene glycol-epoetin beta \[Mircera\]) to maintain hemoglobin. 4. A mean predialysis hemoglobin concentration ≥ 10 g/dL (grams per deciliter) to ≤ 12 g/dL (≥ 100 g/L (grams per liter) to ≤ 120 g/L) obtained from three consecutive days. 4\. A Body Mass Index value ≥ 18.5 kg/m2 (kilograms per m2) at screening. 5. Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures are conducted. 6\. Able to adhere to the study visit schedule and comply with all protocol requirements. Exclusion Criteria: 1. Non renal causes of anemia 2. Subjects on peritoneal dialysis. 3. Systemic hematological disease 4. Uncontrolled diabetes mellitus (HbA1c (hemoglobin A1c) \> 9%) at screening. 5. Uncontrolled hypertension defined as mean of home systolic blood pressure \> 160 mm Hg (millimeter of mercury) or mean of home diastolic blood pressure \> 90 mm Hg calculated once during the screening period prior to randomization 6. Subjects with heart failure 7. History of malignancy (except excised and cured non-melanoma skin cancer, or cervical carcinoma in situ that was surgically ablated more than 5 years ago). 8. Anticipated or scheduled living donor renal transplant during the course of the study.

Locations (23)

Centre Hospitalier EpiCURA - Clinique Louis Caty de Baudour

Baudour, Belgium

Outcomes

Primary Outcomes

Area Under the Serum Concentration-Time Curve Over Dosing Interval (AUC14d) (14 Days)

Area Under the plasma concentration-time curve over 14-day dosing interval (AUC14) for Sotatercept., The PK population included all participants in the safety population with at least one non-missing plasma concentration data. All analyses of PK data were based on the PK population and participants were analyzed according to the treatment group to which they were randomized.

Time frame: Doses 1-2: predose and postdose at 5 min (IV only) 4 hours, 3, and 7 days after each dose; Doses 3-7: predose, and postdose at 5 min after IV injection after each dose; Final dose: predose and postdose at 5 min (IV only) 4 hours, 3, 7, 14 days after dose

Area Under the Serum Concentration- Time Curve Over From Day 1 to Day 28 (AUC28d)

Area under the plasma concentration-time curve over 28-day dosing interval (AUC28d). All analyses of PK data were based on the PK population and participants were analyzed according to the treatment group to which they were randomized.

Maximum Observed Serum Concentration Obtained From the First Dose (Cmax14d)

Maximum observed serum concentration (Cmax14d) of sotatercept, obtained directly from the observed concentration-time data. The PK population included all participants in the safety population with at least one non-missing plasma concentration data. All analyses of PK data were based on the PK population and participants were analyzed according to the treatment group to which they were randomized.

Maximum Observed Serum Concentration (Cmax28d) Obtained From the Combined First 2 Doses

Data from ClinicalTrials.gov

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Universitaire Ziekenhuizen (UZ) Leuven - Gasthuisberg

Leuven, Belgium

CHR de la CITADELLE

Liège, Belgium

KfH Nierenzentrum Coburg

Coburg, Germany

Gemeinschaftspraxis und Dialysezentrum Karlstrass

Düsseldorf, Germany

KfH Kuratorium für Dialyse und Nierentransplantation e.v.

München, Germany

KfH Nierenzentrum Rosenheim

Rosenheim, Germany

Nephrocare Faro

Faro, Portugal

Hospital de Santa Maria

Lisbon, Portugal

Nephrocare Portimao

Portimão, Portugal

...and 13 more locations

Maximum observed serum concentration (Cmax28d) of sotatercept, obtained directly from the observed concentration-time data combining the profiles following the first two doses. The PK population included all participants in the safety population with at least one non-missing plasma concentration data. All analyses of PK data were based on the PK population and participants were analyzed according to the treatment group to which they were randomized.

Time to Reach Maximum Observed Serum Concentration (Tmax)

Time to maximum serum concentration (Tmax) of sotatercept, obtained directly from the observed concentration-time data. The PK population included all participants in the safety population with at least one non-missing plasma concentration data. All analyses of PK data were based on the PK population and participants were analyzed according to the treatment group to which they were randomized.

Time frame: Doses 1-2: pre- and postdose at 5 min (IV only) 4 hrs, 3, and 7 days after each dose; Doses 3-7: pre-, and postdose at 5 min after IV injection after each dose; Final dose: pre- and postdose at 5 min (IV only), 4 hrs, 3, 7, 14, 28, 56, 84, and 112 days

Estimate of Terminal Elimination Half-Life in Serum at Final Dose Only (t1/2)

Terminal elimination half-life (T1/2). The PK population included all participants in the safety population with at least one non-missing plasma concentration data. All analyses of PK data were based on the PK population and participants were analyzed according to the treatment group to which they were randomized.

Time frame: Predose and postdose at 5 min (IV only) 4 hours, 3, 7, 14, 28, 56, 84, and 112 days after the final dose.

Lambda (ʎz): Apparent Terminal Rate Constant (at Final Dose Only)

Lambda, apparent terminal rate constant (final dose only). The PK population included all participants in the safety population with at least one non-missing plasma concentration data. All analysis of PK data were based on the PK population and participants were analyzed according to the treatment group to which they were randomized.

Time frame: Predose and postdose at 5 min (IV only) 4 hours, 3, 7, 14, 28, 56, 84, and 112 days after the final dose

Secondary Outcomes

Percentage of Participants With Mean Hemoglobin ≥ 100 g/L to ≤ 120 g/L Without Rescue Medication

The percentage of participants able to maintain a mean (Visit 14 to 17) hemoglobin concentration ≥ 100 g/L to ≤ 120 g/L without the need for rescue medication at each dose level. Mean hemoglobin value is a mean of hemoglobin concentrations from Visit 14 to Visit 17 (days 99 to 113).

Time frame: Visit 14 to Visit 17 (days 99 to 113)

Change From Baseline in Mean Hemoglobin Concentration for Visit 14 to 17 (All Participants Regardless of Rescue)

Change in mean hemoglobin concentration between baseline and Visit 14 to 17 at each dose level. Baseline hemoglobin value is the mean of three consecutive hemoglobin concentrations with the last hemoglobin concentration done within the 7 days prior to randomization and the value obtained on the day of randomization. Visit 14 to 17 hemoglobin value is a mean of hemoglobin concentrations from Day 99 \[Visit 14\] to Day 113 \[Visit 17\].

Time frame: Baseline and Visit 14 to Visit 17 (days 99 to 113)

Change From Baseline in Mean Hemoglobin Concentration for Visit 14 to 17 (Participants Not Rescued Prior to Day 115)

Change in mean hemoglobin concentration between baseline and Visit 14 to 17 at each dose level for participants not rescued prior to Day 115. Baseline hemoglobin value is the mean of three consecutive hemoglobin concentrations with the last hemoglobin concentration done within the 7 days prior to randomization and the value obtained on the day of randomization. Visit 14 to 17 hemoglobin value is a mean of hemoglobin concentrations from Day 99 \[Visit 14\] to Day 113 \[Visit 17\].

Time frame: Baseline and Visit 14 to Visit 17 (days 99 to 113)

Number of Participants With Adverse Events (AEs)

Treatment-emergent adverse event (TEAE) was defined as an adverse event with start date on or after date of first dose of study drug. An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participants during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values, regardless of etiology. A serious adverse event is defined as any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. Severity and intensity was assessed using the following grading scale: Mild, Moderate and Severe (could be non-serious or serious).

Time frame: From date of first dose of investigational product to 112 days after the last dose or until the last study visit, whichever period was longer. The maximum duration for any IV or SC dose was 114 days. Up to approximately 226 days.