Clinical trial NCT01999582: A Phase 2 Study of Intravenous or Subcutaneous Dosing of Sotatercept (ACE-011) in Patients With End-Stage Kidney Disease on Hemodialysis
Official title: A Phase 2 Multicenter, Randomized, Open-Label , Multiple-Dose Study of Intravenous and Subcutaneous Administration of Sotatercept (ACE-011) in Subjects With End-Stage Kidney Disease on Hemodialysis Switched From Erythropoeisis Stimulating Agents With Staggered Dose Group Escalation in Part 1 Followed by a Parallel Group, Active Controlled Study of Selected Dose(s) and Regimen(s) in Part 2: To Evaluate the Pharmacokinetics, Safety, Tolerability, Efficacy, Dosing Regimen, and Pharmacodynamics of Sotatercept
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Anemia
Kidney Failure, Chronic
Keywords: Anemia
End Stage Kidney Disease
Chronic Kidney Disease
Dialysis
Erythrpoietin Stimulating Agent (ESA)
Lead sponsor: Celgene
Sponsor class: INDUSTRY
First posted: 2013-12-03
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Area Under the Serum Concentration-Time Curve Over Dosing Interval (AUC14d) (14 Days)
timeFrame: 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
measure: Area Under the Serum Concentration- Time Curve Over From Day 1 to Day 28 (AUC28d)
timeFrame: 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
measure: Maximum Observed Serum Concentration Obtained From the First Dose (Cmax14d)
timeFrame: 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
measure: Maximum Observed Serum Concentration (Cmax28d) Obtained From the Combined First 2 Doses
timeFrame: 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
measure: Time to Reach Maximum Observed Serum Concentration (Tmax)
timeFrame: 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
measure: Estimate of Terminal Elimination Half-Life in Serum at Final Dose Only (t1/2)
timeFrame: Predose and postdose at 5 min (IV only) 4 hours, 3, 7, 14, 28, 56, 84, and 112 days after the final dose.
measure: Lambda (ʎz): Apparent Terminal Rate Constant (at Final Dose Only)
timeFrame: 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:
measure: Percentage of Participants With Mean Hemoglobin ≥ 100 g/L to ≤ 120 g/L Without Rescue Medication
timeFrame: Visit 14 to Visit 17 (days 99 to 113)
measure: Change From Baseline in Mean Hemoglobin Concentration for Visit 14 to 17 (All Participants Regardless of Rescue)
timeFrame: Baseline and Visit 14 to Visit 17 (days 99 to 113)
measure: Change From Baseline in Mean Hemoglobin Concentration for Visit 14 to 17 (Participants Not Rescued Prior to Day 115)
timeFrame: Baseline and Visit 14 to Visit 17 (days 99 to 113)
measure: Number of Participants With Adverse Events (AEs)
timeFrame: 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.
Other outcomes:
Locations:
city: Baudour
country: Belgium
facility: Centre Hospitalier EpiCURA - Clinique Louis Caty de Baudour
city: Leuven
country: Belgium
facility: Universitaire Ziekenhuizen (UZ) Leuven - Gasthuisberg
city: Liege
country: Belgium
facility: CHR de la CITADELLE
city: Coburg
country: Germany
facility: KfH Nierenzentrum Coburg
city: Düsseldorf
country: Germany
facility: Gemeinschaftspraxis und Dialysezentrum Karlstrass
city: München
country: Germany
facility: KfH Kuratorium für Dialyse und Nierentransplantation e.v.
city: Rosenheim
country: Germany
facility: KfH Nierenzentrum Rosenheim
city: Faro
country: Portugal
facility: Nephrocare Faro
city: Lisboa
country: Portugal
facility: Hospital de Santa Maria
city: Portimão
country: Portugal
facility: Nephrocare Portimao
city: Almeria
country: Spain
facility: Complejo Hospitalario de Torrecardenas
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Clinic of Barcelona
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofia
city: Galdakao
country: Spain
facility: Hospital Galdakao-Usansolo
city: Madrid
country: Spain
facility: Servicio de Nefrologia Hospital General Universitario Gregorio Maranon
city: Madrid
country: Spain
facility: Hospital 12 de Octubre
city: Majadahonda, Madrid
country: Spain
facility: Hospital Universitario Puerta de Hierro Majadahonda
city: Santander, Cantabria
country: Spain
facility: Hospital Universitario Marques de Valdecilla
city: Torrevieja (Alicante)
country: Spain
facility: Hospital de Torrevieja
city: Cambridge
country: United Kingdom
facility: Cambridge University Hospitals NHS Trust
city: Glasgow
country: United Kingdom
facility: Glasgow Royal Infirmary
city: London
country: United Kingdom
facility: St Georges Healthcare NHS Trust
Study officials:
affiliation: Celgene Corporation
name: William Smith, MD
role: STUDY_DIRECTOR
References: