Back to resultsA Phase 2 Study of Intravenous or Subcutaneous Dosing of Sotatercept (ACE-011) in Patients With End-Stage Kidney Disease on Hemodialysis
Primary Purpose
Anemia, Kidney Failure, Chronic
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Sotatercept
Sotatercept
Sponsored by
About this trial
This is an interventional treatment trial for Anemia focused on measuring Anemia, End Stage Kidney Disease, Chronic Kidney Disease, Dialysis, Erythrpoietin Stimulating Agent (ESA)
Eligibility Criteria
Inclusion Criteria:
- Males or females ≥ 18 years of age.
- Subjects on at least 6 hours of hemodialysis per week, for at least 12 weeks before screening
- Subjects must be on a stable intravenous or subcutaneous dose of Erythropoietin Stimulating Agents (excluding methoxy polyethylene glycol-epoetin beta [Mircera]) to maintain hemoglobin.
- 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:
- Non renal causes of anemia
- Subjects on peritoneal dialysis.
- Systemic hematological disease
- Uncontrolled diabetes mellitus (HbA1c (hemoglobin A1c) > 9%) at screening.
- 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
- Subjects with heart failure
- 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).
- Anticipated or scheduled living donor renal transplant during the course of the study.
Sites / Locations
- Centre Hospitalier EpiCURA - Clinique Louis Caty de Baudour
- Universitaire Ziekenhuizen (UZ) Leuven - Gasthuisberg
- CHR de la CITADELLE
- KfH Nierenzentrum Coburg
- Gemeinschaftspraxis und Dialysezentrum Karlstrass
- KfH Kuratorium für Dialyse und Nierentransplantation e.v.
- KfH Nierenzentrum Rosenheim
- Nephrocare Faro
- Hospital de Santa Maria
- Nephrocare Portimao
- Complejo Hospitalario de Torrecardenas
- Hospital Universitari Vall d'Hebron
- Hospital Clinic of Barcelona
- Hospital Universitario Reina Sofia
- Hospital Galdakao-Usansolo
- Servicio de Nefrologia Hospital General Universitario Gregorio Maranon
- Hospital 12 de Octubre
- Hospital Universitario Puerta de Hierro Majadahonda
- Hospital Universitario Marques de Valdecilla
- Hospital de Torrevieja
- Cambridge University Hospitals NHS Trust
- Glasgow Royal Infirmary
- St Georges Healthcare NHS Trust
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Intravenous Dose Group 1, 2, and 3
Subcutaneous Dose Group 1, 2, and 3
Arm Description
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)
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)
Outcomes
Primary Outcome Measures
Pharmacokinetics (Cmax)
Maximum observed concentration in serum
Pharmacokinetics (Tmax)
Time to maximum concentration
Pharmacokinetics (AUC 28d)
Area under the concentration-time curve
Pharmacokinetics (t1/2,z)
Terminal half life
Adverse Event
treatment emergent adverse sevents (TEAEs) and number of subjects with TEAEs.
Secondary Outcome Measures
Efficacy
Change in mean hemoglobin concentration between baseline and day 113
Bone Turnover
Change in serum bone biomarker concentrations between baseline and end of study (day 211)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01999582
Brief Title
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
2. Study Status
Record Verification Date
February 2017
Overall Recruitment Status
Completed
Study Start Date
November 2013 (undefined)
Primary Completion Date
August 2016 (Actual)
Study Completion Date
August 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Celgene
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Anemia, Kidney Failure, Chronic
Keywords
Anemia, End Stage Kidney Disease, Chronic Kidney Disease, Dialysis, Erythrpoietin Stimulating Agent (ESA)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
49 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Intravenous Dose Group 1, 2, and 3
Arm Type
Experimental
Arm Description
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)
Arm Title
Subcutaneous Dose Group 1, 2, and 3
Arm Type
Experimental
Arm Description
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)
Intervention Type
Biological
Intervention Name(s)
Sotatercept
Other Intervention Name(s)
ACE-011
Intervention Description
Sotatercept is dosed intravenously every 14 days. The dose a subject receives will depend on the randomization arm and the dose group.
Intervention Type
Biological
Intervention Name(s)
Sotatercept
Other Intervention Name(s)
ACE-011
Intervention Description
Sotatercept is dosed subcutaneously every 14 days. The dose a subject receives will depend on the randomization arm and the dose group.
Primary Outcome Measure Information:
Title
Pharmacokinetics (Cmax)
Description
Maximum observed concentration in serum
Time Frame
28 days
Title
Pharmacokinetics (Tmax)
Description
Time to maximum concentration
Time Frame
28 days
Title
Pharmacokinetics (AUC 28d)
Description
Area under the concentration-time curve
Time Frame
28 days
Title
Pharmacokinetics (t1/2,z)
Description
Terminal half life
Time Frame
211 days
Title
Adverse Event
Description
treatment emergent adverse sevents (TEAEs) and number of subjects with TEAEs.
Time Frame
211 days
Secondary Outcome Measure Information:
Title
Efficacy
Description
Change in mean hemoglobin concentration between baseline and day 113
Time Frame
113 days
Title
Bone Turnover
Description
Change in serum bone biomarker concentrations between baseline and end of study (day 211)
Time Frame
211 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Males or females ≥ 18 years of age.
Subjects on at least 6 hours of hemodialysis per week, for at least 12 weeks before screening
Subjects must be on a stable intravenous or subcutaneous dose of Erythropoietin Stimulating Agents (excluding methoxy polyethylene glycol-epoetin beta [Mircera]) to maintain hemoglobin.
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:
Non renal causes of anemia
Subjects on peritoneal dialysis.
Systemic hematological disease
Uncontrolled diabetes mellitus (HbA1c (hemoglobin A1c) > 9%) at screening.
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
Subjects with heart failure
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).
Anticipated or scheduled living donor renal transplant during the course of the study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
William Smith, MD
Organizational Affiliation
Celgene Corporation
Official's Role
Study Director
Facility Information:
Facility Name
Centre Hospitalier EpiCURA - Clinique Louis Caty de Baudour
City
Baudour
ZIP/Postal Code
7331
Country
Belgium
Facility Name
Universitaire Ziekenhuizen (UZ) Leuven - Gasthuisberg
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
CHR de la CITADELLE
City
Liege
ZIP/Postal Code
4000
Country
Belgium
Facility Name
KfH Nierenzentrum Coburg
City
Coburg
ZIP/Postal Code
96450
Country
Germany
Facility Name
Gemeinschaftspraxis und Dialysezentrum Karlstrass
City
Düsseldorf
ZIP/Postal Code
40210
Country
Germany
Facility Name
KfH Kuratorium für Dialyse und Nierentransplantation e.v.
City
München
ZIP/Postal Code
80337
Country
Germany
Facility Name
KfH Nierenzentrum Rosenheim
City
Rosenheim
ZIP/Postal Code
83022
Country
Germany
Facility Name
Nephrocare Faro
City
Faro
ZIP/Postal Code
8000
Country
Portugal
Facility Name
Hospital de Santa Maria
City
Lisboa
ZIP/Postal Code
1649-035
Country
Portugal
Facility Name
Nephrocare Portimao
City
Portimão
ZIP/Postal Code
8500-311
Country
Portugal
Facility Name
Complejo Hospitalario de Torrecardenas
City
Almeria
ZIP/Postal Code
04009
Country
Spain
Facility Name
Hospital Universitari Vall d'Hebron
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hospital Clinic of Barcelona
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
Facility Name
Hospital Universitario Reina Sofia
City
Córdoba
ZIP/Postal Code
14004
Country
Spain
Facility Name
Hospital Galdakao-Usansolo
City
Galdakao
ZIP/Postal Code
48960
Country
Spain
Facility Name
Servicio de Nefrologia Hospital General Universitario Gregorio Maranon
City
Madrid
ZIP/Postal Code
28007
Country
Spain
Facility Name
Hospital 12 de Octubre
City
Madrid
ZIP/Postal Code
28041
Country
Spain
Facility Name
Hospital Universitario Puerta de Hierro Majadahonda
City
Majadahonda, Madrid
ZIP/Postal Code
28222
Country
Spain
Facility Name
Hospital Universitario Marques de Valdecilla
City
Santander, Cantabria
ZIP/Postal Code
39008
Country
Spain
Facility Name
Hospital de Torrevieja
City
Torrevieja (Alicante)
ZIP/Postal Code
03186
Country
Spain
Facility Name
Cambridge University Hospitals NHS Trust
City
Cambridge
ZIP/Postal Code
CB2 0QQ
Country
United Kingdom
Facility Name
Glasgow Royal Infirmary
City
Glasgow
ZIP/Postal Code
G11 6NT
Country
United Kingdom
Facility Name
St Georges Healthcare NHS Trust
City
London
ZIP/Postal Code
SW17 0QT
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
A Phase 2 Study of Intravenous or Subcutaneous Dosing of Sotatercept (ACE-011) in Patients With End-Stage Kidney Disease on Hemodialysis
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