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

Sponsor

Celgene (Industry)

Overall Status

Completed

CT.gov ID

NCT01999582

Collaborator

(none)

Enrollment

Locations

Arms

Duration (Months)

2.1

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Anemia Kidney Failure, Chronic	Biological: Sotatercept Biological: Sotatercept	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

49 participants

Allocation:

Randomized

Intervention Model:

Single Group Assignment

Masking:

None (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

Study Start Date :

Nov 1, 2013

Actual Primary Completion Date :

Aug 1, 2016

Actual Study Completion Date :

Aug 1, 2016

Arms and Interventions

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
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 Names: ACE-011

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

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 Names:

ACE-011

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

Efficacy [113 days]
Change in mean hemoglobin concentration between baseline and day 113
Bone Turnover [211 days]
Change in serum bone biomarker concentrations between baseline and end of study (day 211)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.
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.
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.

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Centre Hospitalier EpiCURA - Clinique Louis Caty de Baudour	Baudour	Belgium	7331
2	Universitaire Ziekenhuizen (UZ) Leuven - Gasthuisberg	Leuven	Belgium	3000
3	CHR de la CITADELLE	Liege	Belgium	4000
4	KfH Nierenzentrum Coburg	Coburg	Germany	96450
5	Gemeinschaftspraxis und Dialysezentrum Karlstrass	Düsseldorf	Germany	40210
6	KfH Kuratorium für Dialyse und Nierentransplantation e.v.	München	Germany	80337
7	KfH Nierenzentrum Rosenheim	Rosenheim	Germany	83022
8	Nephrocare Faro	Faro	Portugal	8000
9	Hospital de Santa Maria	Lisboa	Portugal	1649-035
10	Nephrocare Portimao	Portimão	Portugal	8500-311
11	Complejo Hospitalario de Torrecardenas	Almeria	Spain	04009
12	Hospital Universitari Vall d'Hebron	Barcelona	Spain	08035
13	Hospital Clinic of Barcelona	Barcelona	Spain	08036
14	Hospital Universitario Reina Sofia	Córdoba	Spain	14004
15	Hospital Galdakao-Usansolo	Galdakao	Spain	48960
16	Servicio de Nefrologia Hospital General Universitario Gregorio Maranon	Madrid	Spain	28007
17	Hospital 12 de Octubre	Madrid	Spain	28041
18	Hospital Universitario Puerta de Hierro Majadahonda	Majadahonda, Madrid	Spain	28222
19	Hospital Universitario Marques de Valdecilla	Santander, Cantabria	Spain	39008
20	Hospital de Torrevieja	Torrevieja (Alicante)	Spain	03186
21	Cambridge University Hospitals NHS Trust	Cambridge	United Kingdom	CB2 0QQ
22	Glasgow Royal Infirmary	Glasgow	United Kingdom	G11 6NT
23	St Georges Healthcare NHS Trust	London	United Kingdom	SW17 0QT