A Study to Assess Efficacy and Safety of PF-06462700 in Japanese Participants With Aplastic Anemia

A MULTICENTER, OPEN-LABEL, SINGLE-ARM STUDY TO ASSESS THE EFFICACY AND SAFETY OF PF-06462700 ADMINISTERED INTRAVENOUSLY AT 40 MG/KG/DAY FOR 4 DAYS IN JAPANESE PARTICIPANTS WITH MODERATE AND ABOVE APLASTIC ANEMIA

The purpose of the study is to assess the efficacy and safety of PF-06462700 administered intravenously at 40 mg/kg/day for 4 days in Japanese participants with moderate and above aplastic anemia for making an approval application in Japan.

Study Overview

• Status: Completed
• Conditions: Aplastic Anemia
• Intervention / Treatment: Biological: PF-06462700

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Aichi
    • Nagoya, Aichi, Japan, 466-8560
      • Nagoya University Hospital
  • Tochigi
    • Shimotsuke, Tochigi, Japan, 329 0498
      • Jichi Medical University Hospital
  • Tokyo
    • Shinjuku-ku, Tokyo, Japan, 160-8582
      • Keio University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female participants between the ages of 2 years and more, inclusive, at Visit

  1 (Screening).

• Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
• Have a clinical diagnosis of aplastic anemia by bone marrow aspiration/biopsy findings and/or magnetic resonance imaging (MRI) etc.
• Must meet the following criteria of moderate and above aplastic anemia
• Capable of giving signed informed consent/assent as described in Appendix 1, which includes compliance with the requirements and restrictions listed in the informed consent document (ICD)/assent document and in this protocol.

Exclusion Criteria:

• Eligible and willing to have a sibling allogeneic stem cell transplantation.
• Evidence of a myelodysplastic syndrome (except for refractory cytopenia in children), as well as other primitive marrow disease.
• History or clinical suspicion of congenital aplastic anemia (Fanconi anemia, Congenital keratosis, etc).
• History of malignant tumors with active disease within 5 years from study participation.

• Participants who are clearly infected with hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), and human T-cell leukemia virus type

  1 (HTLV-1).

• Pregnant or breast-feeding participants.
• Participants with severe hepatic, renal or cardiac failure, or any other life-threatening concurrent [aspartate aminotransferase (AST) or alanine aminotransferase (ALT) or total bilirubin values >5 × upper limit of normal (ULN), and/or creatinine value >2 × ULN].
• Participants with hypersensitivity such as shock after skin test of this study drug.
• Participants with uncontrolled severe infection (pneumonia, sepsis, etc).
• Participants who received live vaccine or live attenuated vaccine within 6 weeks prior to the first dose of study drug.
• Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this study.
• Prior immunosuppressive therapy with lymphocyte-depleting agents/therapies, including both non-B-cell selective and B-cell-depleting agents (e.g., alefacept, alemtuzumab, rituximab). However, participants previously treated with rATG may enroll.
• Previous history of stem cell transplantation.
• Previous administration with an investigational drug within 30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of investigational product used in this study (whichever is longer).
• Baseline 12-lead electrocardiogram (ECG) that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results (e.g., baseline corrected QT [QTc] interval >450 msec, complete left bundle branch block [LBBB], signs of an acute or indeterminate-age myocardial infarction, ST-T interval changes suggestive of myocardial ischemia, second- or third-degree atrioventricular [AV] block, or serious bradyarrhythmias or tachyarrhythmias). If the baseline uncorrected QT interval is >450 msec, this interval should be rate-corrected using the Fridericia method and the resulting QTcF should be used for decision making and reporting. If QTc exceeds 450 msec, or QRS exceeds 120 msec, the ECG should be repeated 2 more times and the average of the 3 QTc or QRS values should be used to determine the participant's eligibility. Computer-interpreted ECGs should be overread by a physician experienced in reading ECGs before excluding participants.
• Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or Pfizer employees, including their family members, directly involved in the conduct of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PF-006462700 group; All enrolled participants will be administrated PF-006462700.	Biological: PF-06462700; PF-06462700 is classified as an immunosuppressant/ immunosuppressive agent. It is the purified, concentrated, and sterile gamma globulin, primarily monomeric immunoglobulin G (IgG), from hyperimmune serum of horses that are immunized with human thymus lymphocytes.; Other Names: Brand name in the US: ATGAM

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Hematologic Response at Week 12	Hematologic response was considered to be "effective" when 2 or more of the following criteria were met: absolute neutrophil count greater than or equal to (>=) 500 per microliters, platelet count >=20,000 per microliters and reticulocyte count >=60,000 per microliters was observed. In this outcome measure, number of participants with hematologic response classified as effective and not effective were reported. Improvement in counts that were dependent upon exogenously administered growth factors or transfusion, was not considered as fulfilling response criteria.	Week 12 Follow-up Visit

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Hematologic Response at Week 24	Hematologic response was considered to be "effective" when 2 or more of the following criteria were met: absolute neutrophil count >=500 per microliters, platelet count >=20,000 per microliters and reticulocyte count >=60,000 per microliters was observed. In this outcome measure, number of participants with hematologic response classified as effective and not effective were reported. Improvement in counts that were dependent upon exogenously administered growth factors or transfusion, was not been considered as fulfilling response criteria.	Week 24 Follow-up Visit
Absolute Neutrophil Count at Day 4, Weeks 1, 2, 4, 6, 8, 10, 12, 24		Treatment: Day 4; Follow-up: Week 1, 2, 4, 6, 8, 10, 12, 24
Platelet Count at Day 4, Weeks 1, 2, 4, 6, 8, 10, 12, 24		Treatment: Day 4; Follow-up: Week 1, 2, 4, 6, 8, 10, 12, 24
Reticulocyte Count at Day 4, Weeks 1, 2, 4, 6, 8, 10, 12, 24		Treatment: Day 4; Follow-up: Week 1, 2, 4, 6, 8, 10, 12, 24
Number of Participants Who Survived During the Study	In this outcome measure, number of participants who survived during the study were observed.	Screening (up to 28 days prior to Day 1 of treatment) up to 24 weeks of follow-up (approximately up to 28 weeks)
Number of Participants With Transfusion Independence at Weeks 12 and 24	Transfusion independence at Week 12 was defined as when participants did not have any transfusion records from the time of the first dose of the investigational product at Day 1 to the day of Week 12 follow-up visit (inclusive). Transfusion independence at Week 24 was defined as when participants did not have any transfusion records from the day after Week 12 follow-up visit to the day of Week 24 follow-up visit (inclusive).	Week 12 Transfusion Independence: Day 1 of Treatment up to Week 12 Follow-up Visit (approximately 12 weeks); Week 24 Transfusion Independence: Day after Week 12 Follow-up visit to Week 24 Follow-up Visit (approximately 12 weeks)

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): July 25, 2020
• Primary Completion (Actual): January 22, 2021
• Study Completion (Actual): April 19, 2021

Study Registration Dates

• First Submitted: April 1, 2020
• First Submitted That Met QC Criteria: April 14, 2020
• First Posted (Actual): April 17, 2020

Study Record Updates

• Last Update Posted (Actual): April 27, 2022
• Last Update Submitted That Met QC Criteria: April 1, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Aplastic Anemia, globulin, ATG, Anti-human Thymocyte Immunogloblin
• Additional Relevant MeSH Terms: Bone Marrow Diseases; Hematologic Diseases; Bone Marrow Failure Disorders; Anemia; Anemia, Aplastic
• Other Study ID Numbers: B5411003; ATGAM Japan local ph3 study (Other Identifier: Alias Study Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes