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 ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Celgene Corporation
ClinicalTrials.gov Identifier:
NCT01999582
First received: November 26, 2013
Last updated: May 5, 2016
Last verified: May 2016
  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 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

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)


Enrollment: 49
Study Start Date: November 2013
Estimated Study Completion Date: August 2016
Estimated Primary Completion Date: August 2016 (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 (0.1, 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 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 to 0.5 mg/kg, titrated based on titration rules, 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

Sponsors and Collaborators
Celgene Corporation
Investigators
Study Director: William Smith, MD Celgene Corporation
  More Information

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: May 5, 2016
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 Diseases
Kidney Failure, Chronic
Renal Insufficiency
Renal Insufficiency, Chronic
Urologic Diseases

ClinicalTrials.gov processed this record on May 26, 2016