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

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

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 Overview

• Status: Completed
• Conditions: Anemia; Kidney Failure, Chronic
• Intervention / Treatment: Biological: Sotatercept; Biological: Sotatercept

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Baudour, Belgium, 7331
    • Centre Hospitalier EpiCURA - Clinique Louis Caty de Baudour
  • Leuven, Belgium, 3000
    • Universitaire Ziekenhuizen (UZ) Leuven - Gasthuisberg
  • Liege, Belgium, 4000
    • CHR de la Citadelle
• Germany
  • Coburg, Germany, 96450
    • KfH Nierenzentrum Coburg
  • Düsseldorf, Germany, 40210
    • Gemeinschaftspraxis und Dialysezentrum Karlstrass
  • München, Germany, 80337
    • KfH Kuratorium für Dialyse und Nierentransplantation e.V.
  • Rosenheim, Germany, 83022
    • KfH Nierenzentrum Rosenheim
• Portugal
  • Faro, Portugal, 8000
    • Nephrocare Faro
  • Lisboa, Portugal, 1649-035
    • Hospital De Santa Maria
  • Portimão, Portugal, 8500-311
    • Nephrocare Portimao
• Spain
  • Almeria, Spain, 04009
    • Complejo Hospitalario de Torrecardenas
  • Barcelona, Spain, 08036
    • Hospital Clinic of Barcelona
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Córdoba, Spain, 14004
    • Hospital Universitario Reina Sofia
  • Galdakao, Spain, 48960
    • Hospital Galdakao-Usansolo
  • Madrid, Spain, 28041
    • Hospital 12 de Octubre
  • Madrid, Spain, 28007
    • Servicio de Nefrología Hospital General universitario Gregorio Maranon
  • Majadahonda, Madrid, Spain, 28222
    • Hospital Universitario Puerta de Hierro Majadahonda
  • Santander, Cantabria, Spain, 39008
    • Hospital Universitario Marques de Valdecilla
  • Torrevieja (Alicante), Spain, 03186
    • Hospital de Torrevieja
• United Kingdom
  • Cambridge, United Kingdom, CB2 0QQ
    • Cambridge University Hospitals NHS Trust
  • Glasgow, United Kingdom, G11 6NT
    • Glasgow Royal Infirmary
  • London, United Kingdom, SW17 0QT
    • St Georges Healthcare NHS Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intravenous Dose Group 1, 2, and 3; Intravenous Dose Group 1 starting at 0.1 mg/kg and escalated in Dose Groups 2 (0.2 mg/kg) and Dose Group 3 (0.1, 0.2, 0.3, 0.4 mg/kg, titrated based on titration rules, administered every 14 days)	Biological: Sotatercept; Sotatercept is dosed intravenously every 14 days. The dose a subject receives will depend on the randomization arm and the dose group.; Other Names: ACE-011; Biological: Sotatercept; Sotatercept is dosed subcutaneously every 14 days. The dose a subject receives will depend on the randomization arm and the dose group.; Other Names: ACE-011
Experimental: Subcutaneous Dose Group 1, 2, and 3; Subcutaneous Dose Group 1 starting at 0.13 mg/kg and escalated in Dose Groups 2 (0.26 mg/kg) and Dose Group 3 (0.4 to 0.5 mg/kg, titrated based on titration rules, administered every14 days)	Biological: Sotatercept; Sotatercept is dosed intravenously every 14 days. The dose a subject receives will depend on the randomization arm and the dose group.; Other Names: ACE-011; Biological: Sotatercept; Sotatercept is dosed subcutaneously every 14 days. The dose a subject receives will depend on the randomization arm and the dose group.; Other Names: ACE-011

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics (Cmax)	Maximum observed concentration in serum	28 days
Pharmacokinetics (Tmax)	Time to maximum concentration	28 days
Pharmacokinetics (AUC 28d)	Area under the concentration-time curve	28 days
Pharmacokinetics (t1/2,z)	Terminal half life	211 days
Adverse Event	treatment emergent adverse sevents (TEAEs) and number of subjects with TEAEs.	211 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy	Change in mean hemoglobin concentration between baseline and day 113	113 days
Bone Turnover	Change in serum bone biomarker concentrations between baseline and end of study (day 211)	211 days

Collaborators and Investigators

• Sponsor: Celgene

Study record dates

Study Major Dates

• Study Start: November 1, 2013
• Primary Completion (Actual): August 1, 2016
• Study Completion (Actual): August 1, 2016

Study Registration Dates

• First Submitted: November 26, 2013
• First Submitted That Met QC Criteria: November 26, 2013
• First Posted (Estimate): December 3, 2013

Study Record Updates

• Last Update Posted (Actual): February 16, 2017
• Last Update Submitted That Met QC Criteria: February 14, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: Anemia; Chronic Kidney Disease; Dialysis; End Stage Kidney Disease; Erythrpoietin Stimulating Agent (ESA)
• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency, Chronic; Kidney Diseases; Kidney Failure, Chronic; Renal Insufficiency
• Other Study ID Numbers: ACE-011-REN-002; 2012-003788-23 (EudraCT Number)