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

NCT01999582 | Completed Phase 2 Results

• 2 other identifiers: ACE-011-REN-0022012-003788-23
• Study Type: interventional
• Target: 50
• Locations: 5 countries
• Sites: 23

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.

Conditions

Anemia; Kidney Failure, Chronic

Keywords

Anemia; End Stage Kidney Disease; Chronic Kidney Disease; Dialysis; Erythrpoietin Stimulating Agent (ESA)

Outcome Measures

Primary Outcomes (7)

• Area Under the Serum Concentration-Time Curve Over Dosing Interval (AUC14d) (14 Days)

  Area Under the plasma concentration-time curve over 14-day dosing interval (AUC14) for Sotatercept., The PK population included all participants in the safety population with at least one non-missing plasma concentration data. All analyses of PK data were based on the PK population and participants were analyzed according to the treatment group to which they were randomized.

  Doses 1-2: predose and postdose at 5 min (IV only) 4 hours, 3, and 7 days after each dose; Doses 3-7: predose, and postdose at 5 min after IV injection after each dose; Final dose: predose and postdose at 5 min (IV only) 4 hours, 3, 7, 14 days after dose

• Area Under the Serum Concentration- Time Curve Over From Day 1 to Day 28 (AUC28d)

  Area under the plasma concentration-time curve over 28-day dosing interval (AUC28d). All analyses of PK data were based on the PK population and participants were analyzed according to the treatment group to which they were randomized.

  Doses 1-2: predose and postdose at 5 min (IV only) 4 hours, 3, and 7 days after each dose; Doses 3-7: predose, and postdose at 5 min after IV injection after each dose; Final dose: predose and postdose at 5 min (IV only) 4 hours, 3, 7, 14 days after dose

• Maximum Observed Serum Concentration Obtained From the First Dose (Cmax14d)

  Maximum observed serum concentration (Cmax14d) of sotatercept, obtained directly from the observed concentration-time data. The PK population included all participants in the safety population with at least one non-missing plasma concentration data. All analyses of PK data were based on the PK population and participants were analyzed according to the treatment group to which they were randomized.

  Doses 1-2: predose and postdose at 5 min (IV only) 4 hours, 3, and 7 days after each dose; Doses 3-7: predose, and postdose at 5 min after IV injection after each dose; Final dose: predose and postdose at 5 min (IV only) 4 hours, 3, 7, 14 days after dose

• Maximum Observed Serum Concentration (Cmax28d) Obtained From the Combined First 2 Doses

  Maximum observed serum concentration (Cmax28d) of sotatercept, obtained directly from the observed concentration-time data combining the profiles following the first two doses. The PK population included all participants in the safety population with at least one non-missing plasma concentration data. All analyses of PK data were based on the PK population and participants were analyzed according to the treatment group to which they were randomized.

  Doses 1-2: predose and postdose at 5 min (IV only) 4 hours, 3, and 7 days after each dose; Doses 3-7: predose, and postdose at 5 min after IV injection after each dose; Final dose: predose and postdose at 5 min (IV only) 4 hours, 3, 7, 14 days after dose

• Time to Reach Maximum Observed Serum Concentration (Tmax)

  Time to maximum serum concentration (Tmax) of sotatercept, obtained directly from the observed concentration-time data. The PK population included all participants in the safety population with at least one non-missing plasma concentration data. All analyses of PK data were based on the PK population and participants were analyzed according to the treatment group to which they were randomized.

  Doses 1-2: pre- and postdose at 5 min (IV only) 4 hrs, 3, and 7 days after each dose; Doses 3-7: pre-, and postdose at 5 min after IV injection after each dose; Final dose: pre- and postdose at 5 min (IV only), 4 hrs, 3, 7, 14, 28, 56, 84, and 112 days

• Estimate of Terminal Elimination Half-Life in Serum at Final Dose Only (t1/2)

  Terminal elimination half-life (T1/2). The PK population included all participants in the safety population with at least one non-missing plasma concentration data. All analyses of PK data were based on the PK population and participants were analyzed according to the treatment group to which they were randomized.

  Predose and postdose at 5 min (IV only) 4 hours, 3, 7, 14, 28, 56, 84, and 112 days after the final dose.

• Lambda (ʎz): Apparent Terminal Rate Constant (at Final Dose Only)

  Lambda, apparent terminal rate constant (final dose only). The PK population included all participants in the safety population with at least one non-missing plasma concentration data. All analysis of PK data were based on the PK population and participants were analyzed according to the treatment group to which they were randomized.

  Predose and postdose at 5 min (IV only) 4 hours, 3, 7, 14, 28, 56, 84, and 112 days after the final dose

Secondary Outcomes (4)

• Percentage of Participants With Mean Hemoglobin ≥ 100 g/L to ≤ 120 g/L Without Rescue Medication

  Visit 14 to Visit 17 (days 99 to 113)

• Change From Baseline in Mean Hemoglobin Concentration for Visit 14 to 17 (All Participants Regardless of Rescue)

  Baseline and Visit 14 to Visit 17 (days 99 to 113)

• Change From Baseline in Mean Hemoglobin Concentration for Visit 14 to 17 (Participants Not Rescued Prior to Day 115)

  Baseline and Visit 14 to Visit 17 (days 99 to 113)

• Number of Participants With Adverse Events (AEs)

  From date of first dose of investigational product to 112 days after the last dose or until the last study visit, whichever period was longer. The maximum duration for any IV or SC dose was 114 days. Up to approximately 226 days.

Study Arms (2)

Intravenous Dose Group 1, 2, and 3

EXPERIMENTAL

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

Subcutaneous Dose Group 1, 2, and 3

EXPERIMENTAL

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

Interventions

Sotatercept BIOLOGICAL

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

Also known as: ACE-011

Intravenous Dose Group 1, 2, and 3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Celgene: lead

Study Sites (23)

Centre Hospitalier EpiCURA - Clinique Louis Caty de Baudour

Baudour, 7331, Belgium

Location

Universitaire Ziekenhuizen (UZ) Leuven - Gasthuisberg

Leuven, 3000, Belgium

Location

CHR de la CITADELLE

Liège, 4000, Belgium

Location

KfH Nierenzentrum Coburg

Coburg, 96450, Germany

Location

Gemeinschaftspraxis und Dialysezentrum Karlstrass

Düsseldorf, 40210, Germany

Location

KfH Kuratorium für Dialyse und Nierentransplantation e.v.

München, 80337, Germany

Location

KfH Nierenzentrum Rosenheim

Rosenheim, 83022, Germany

Location

Nephrocare Faro

Faro, 8000, Portugal

Location

Hospital de Santa Maria

Lisbon, 1649-035, Portugal

Location

Nephrocare Portimao

Portimão, 8500-311, Portugal

Location

Complejo Hospitalario de Torrecardenas

Almería, 04009, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Clinic of Barcelona

Barcelona, 08036, Spain

Location

Hospital Universitario Reina Sofia

Córdoba, 14004, Spain

Location

Hospital Galdakao-Usansolo

Galdakao, 48960, Spain

Location

Servicio de Nefrologia Hospital General Universitario Gregorio Maranon

Madrid, 28007, Spain

Location

Hospital 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario Puerta de Hierro Majadahonda

Majadahonda, Madrid, 28222, Spain

Location

Hospital Universitario Marques de Valdecilla

Santander, Cantabria, 39008, Spain

Location

Hospital de Torrevieja

Torrevieja (Alicante), 03186, Spain

Location

Cambridge University Hospitals NHS Trust

Cambridge, CB2 0QQ, United Kingdom

Location

Glasgow Royal Infirmary

Glasgow, G11 6NT, United Kingdom

Location

St Georges Healthcare NHS Trust

London, SW17 0QT, United Kingdom

Location

MeSH Terms

Conditions

Anemia; Kidney Failure, Chronic; Renal Insufficiency, Chronic

Interventions

ACE-011

Condition Hierarchy (Ancestors)

Hematologic Diseases; Hemic and Lymphatic Diseases; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

Due to a shift in the clinical development strategy for the renal sotatercept program, Part 2 of the study was not conducted; Part 2 objectives were not assessed and none of the statistical analyses in Part 2 were conducted; no safety concerns.

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Please email

Study Officials

• William Smith, MD

  Celgene Corporation

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 26, 2013
• First Posted: December 3, 2013
• Study Start: November 30, 2013
• Primary Completion: August 31, 2016
• Study Completion: August 31, 2016
• Last Updated: June 24, 2024
• Results First Posted: June 24, 2024

Record last verified: 2024-01

Locations

ES (10); GB (3); PT (3); DE (4); BE (3)