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

Anemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01999582
• Other study ID #: ACE-011-REN-002
• Secondary ID: 2012-003788-23
• Status: Completed
• Phase: Phase 2
• First received: November 26, 2013
• Last updated: February 14, 2017
• Start date: November 2013
• Est. completion date: August 2016

Study information

• Verified date: February 2017
• Source: Celgene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 49
• Est. completion date: August 2016
• Est. primary completion date: August 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Anemia
• Kidney Diseases
• Kidney Failure, Chronic
• Renal Insufficiency
• Renal Insufficiency, Chronic

Intervention

Biological:
• Sotatercept
Sotatercept is dosed intravenously every 14 days. The dose a subject receives will depend on the randomization arm and the dose group.
• Sotatercept
Sotatercept is dosed subcutaneously every 14 days. The dose a subject receives will depend on the randomization arm and the dose group.

Locations

Country	Name	City	State
Belgium	Centre Hospitalier EpiCURA - Clinique Louis Caty de Baudour	Baudour
Belgium	Universitaire Ziekenhuizen (UZ) Leuven - Gasthuisberg	Leuven
Belgium	CHR de la CITADELLE	Liege
Germany	KfH Nierenzentrum Coburg	Coburg
Germany	Gemeinschaftspraxis und Dialysezentrum Karlstrass	Düsseldorf
Germany	KfH Kuratorium für Dialyse und Nierentransplantation e.v.	München
Germany	KfH Nierenzentrum Rosenheim	Rosenheim
Portugal	Nephrocare Faro	Faro
Portugal	Hospital de Santa Maria	Lisboa
Portugal	Nephrocare Portimao	Portimão
Spain	Complejo Hospitalario de Torrecardenas	Almeria
Spain	Hospital Clinic of Barcelona	Barcelona
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Hospital Universitario Reina Sofia	Córdoba
Spain	Hospital Galdakao-Usansolo	Galdakao
Spain	Hospital 12 de Octubre	Madrid
Spain	Servicio de Nefrologia Hospital General Universitario Gregorio Maranon	Madrid
Spain	Hospital Universitario Puerta de Hierro Majadahonda	Majadahonda, Madrid
Spain	Hospital Universitario Marques de Valdecilla	Santander, Cantabria
Spain	Hospital de Torrevieja	Torrevieja (Alicante)
United Kingdom	Cambridge University Hospitals NHS Trust	Cambridge
United Kingdom	Glasgow Royal Infirmary	Glasgow
United Kingdom	St Georges Healthcare NHS Trust	London

Sponsors (1)

Lead Sponsor	Collaborator
Celgene

Countries where clinical trial is conducted

Belgium,  Germany,  Portugal,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pharmacokinetics (Cmax)	Maximum observed concentration in serum	28 days
Primary	Pharmacokinetics (Tmax)	Time to maximum concentration	28 days
Primary	Pharmacokinetics (AUC 28d)	Area under the concentration-time curve	28 days
Primary	Pharmacokinetics (t1/2,z)	Terminal half life	211 days
Primary	Adverse Event	treatment emergent adverse sevents (TEAEs) and number of subjects with TEAEs.	211 days
Secondary	Efficacy	Change in mean hemoglobin concentration between baseline and day 113	113 days
Secondary	Bone Turnover	Change in serum bone biomarker concentrations between baseline and end of study (day 211)	211 days