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

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Celgene Corporation
Sponsor:
Information provided by (Responsible Party):
Celgene Corporation
ClinicalTrials.gov Identifier:
NCT01999582
First received: November 26, 2013
Last updated: April 1, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Anemia
Kidney Failure, Chronic
Biological: Sotatercept
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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 Erythropoiesis 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

Resource links provided by NLM:


Further study details as provided by Celgene Corporation:

Primary Outcome Measures:
  • Pharmacokinetics (Cmax) [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    Maximum observed concentration in serum

  • Pharmacokinetics (Tmax) [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    Time to maximum concentration

  • Pharmacokinetics (AUC 28d) [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    Area under the concentration-time curve

  • Pharmacokinetics (t1/2,z) [ Time Frame: 211 days ] [ Designated as safety issue: No ]
    Terminal half life

  • Adverse Event [ Time Frame: 211 days ] [ Designated as safety issue: Yes ]
    treatment emergent adverse sevents (TEAEs) and number of subjects with TEAEs.


Secondary Outcome Measures:
  • Efficacy [ Time Frame: 113 days ] [ Designated as safety issue: No ]
    Change in mean hemoglobin concentration between baseline and day 113

  • Bone Turnover [ Time Frame: 211 days ] [ Designated as safety issue: No ]
    Change in serum bone biomarker concentrations between baseline and end of study (day 211)


Estimated Enrollment: 60
Study Start Date: October 2013
Estimated Study Completion Date: October 2015
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 (0.3 mg/kg) 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 Name: 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 mg/kg), administered every14 days
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 Name: ACE-011

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01999582

Contacts
Contact: Daniel Aversa, BS 1-732-652-5671 daversa@celgene.com
Contact: Yemisi Coker, Bsc (Hons) +41 32 729 8754 ycoker@celgene.com

Locations
Belgium
Centre Hospitalier EpiCURA - Clinique Louis Caty de Baudour, Recruiting
Baudour, Belgium, 7331
Universitaire Ziekenhuizen (UZ) Leuven - Gasthuisberg, Recruiting
Leuven, Belgium, 3000
CHR de la CITADELLE, Recruiting
Liege, Belgium, 4000
Germany
KfH Nierenzentrum Coburg Recruiting
Coburg, Germany, 96450
Gemeinschaftspraxis und Dialysezentrum Karlstraße Recruiting
Düsseldorf, Germany, 40210
KfH Nierenzentrum Recruiting
München, Germany, 8084
KfH Nierenzentrum Rosenheim Recruiting
Rosenheim, Germany, 83022
Portugal
Nephrocare Faro Recruiting
Faro, Portugal, 8000
Hospital de Santa Maria Recruiting
Lisboa, Portugal, 1649-035
Nephrocare Portimão Recruiting
Portimão, Portugal, 8500-311
Spain
Complejo Hospitalario de Torrecárdenas. Recruiting
Almeria, Spain, 04009
Hospital Clinic of Barcelona Recruiting
Barcelona, Spain, 08036
Hospital Universitari Vall d'Hebron Recruiting
Barcelona, Spain, 08035
Hospital Galdakao-Usansolo Recruiting
Galdakao, Spain, 48960
Hospital General Universitario Gregorio Marañon Recruiting
Madrid, Spain, 28007
Hospital 12 de Octubre, Fundación para la Investigación Biomédica Recruiting
Madrid, Spain, 28041
Hospital de Torrevieja Recruiting
Torrevieja (Alicante), Spain, 03186
United Kingdom
Glasgow Royal Infirmary Recruiting
Glasgow, United Kingdom, G11 6NT
St. George's Healthcare NHS Trust Recruiting
London, United Kingdom, SW17 0QT
Sponsors and Collaborators
Celgene Corporation
Investigators
Study Director: William Smith, MD Celgene Corporation
  More Information

No publications provided

Responsible Party: Celgene Corporation
ClinicalTrials.gov Identifier: NCT01999582     History of Changes
Other Study ID Numbers: ACE-011-REN-002, 2012-003788-23
Study First Received: November 26, 2013
Last Updated: April 1, 2014
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products
Germany: Federal Institute for Drugs and Medical Devices
Portugal: National Pharmacy and Medicines Institute
Spain: Agencia Española de Medicamentos y Productos Sanitarios
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Celgene Corporation:
Anemia
End Stage Kidney Disease
Chronic Kidney Disease
Dialysis
Erythrpoietin Stimulating Agent (ESA)

Additional relevant MeSH terms:
Kidney Failure, Chronic
Anemia
Kidney Diseases
Renal Insufficiency
Hematologic Diseases
Urologic Diseases
Renal Insufficiency, Chronic
Hematinics
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 22, 2014