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

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04350606
• Collaborator: (none)
• Enrollment: 3
• Locations: 3
• Arm: 1
• Actual Duration (Months): 8.8
• Patient Per Site: 1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Aplastic Anemia	Biological: PF-06462700	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 3 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: Jul 25, 2020
• Actual Primary Completion Date: Jan 22, 2021
• Actual Study Completion Date: Apr 19, 2021

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Hematologic Response at Week 12 [Week 12 Follow-up Visit]

   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.

Secondary Outcome Measures

1. Number of Participants With Hematologic Response at Week 24 [Week 24 Follow-up Visit]

   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.

2. 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]

3. 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]

4. 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]

5. Number of Participants Who Survived During the Study [Screening (up to 28 days prior to Day 1 of treatment) up to 24 weeks of follow-up (approximately up to 28 weeks)]

   In this outcome measure, number of participants who survived during the study were observed.

6. Number of Participants With Transfusion Independence at Weeks 12 and 24 [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)]

   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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 2 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Nagoya University Hospital	Nagoya	Aichi	Japan	466-8560
2	Jichi Medical University Hospital	Shimotsuke	Tochigi	Japan	329 0498
3	Keio University Hospital	Shinjuku-ku	Tokyo	Japan	160-8582

Sponsors and Collaborators

• Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

• Study Protocol - Dec 24, 2019
• Statistical Analysis Plan - May 7, 2021

More Information

Additional Information:

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

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT04350606
• Other Study ID Numbers: B5411003; ATGAM Japan local ph3 study
• First Posted: Apr 17, 2020
• Last Update Posted: Apr 27, 2022
• Last Verified: Mar 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• 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
• Keywords provided by Pfizer: Aplastic Anemia, globulin, ATG, Anti-human Thymocyte Immunogloblin
• Additional relevant MeSH terms: Anemia; Anemia, Aplastic

Study Results

Participant Flow

Pre-assignment Detail	Total 3 participants signed the inform consent form (ICF). Out of which 0 participants were screen failures, 3 actually enrolled into the study and assigned to a study treatment.

Arm/Group Title	PF-06462700
Arm/Group Description	Participants aged 2 years or greater than (>) 2 years with moderate and above severity aplastic anemia received PF-06462700 at a dose of 40 milligram per kilogram per day (mg/kg/day), intravenously (IV) for 4 days. Participants after treatment were followed up for 24 weeks.
Period Title: Overall Study
STARTED	3
Treated	3
Follow-up	3
COMPLETED	3
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	PF-06462700
Arm/Group Description	Participants aged 2 years or >2 years with moderate and above severity aplastic anemia received PF-06462700 at a dose of 40 mg/kg/day, IV for 4 days. Participants after treatment were followed up for 24 weeks.
Overall Participants	3
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	29.67 (16.56)
Sex: Female, Male (Count of Participants)
Female	2 66.7%
Male	1 33.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	3 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	3 100%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	0 0%
More than one race	0 0%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Hematologic Response at Week 12
Description	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.
Time Frame	Week 12 Follow-up Visit

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) included participants were assigned to investigational product and who took at least 1 dose of investigational product.

Arm/Group Title	PF-06462700
Arm/Group Description	Participants aged 2 years or >2 years with moderate and above severity aplastic anemia received PF-06462700 at a dose of 40 mg/kg/day, IV for 4 days. Participants after treatment were followed up for 24 weeks.
Measure Participants	3
Effective	2 66.7%
Not Effective	1 33.3%

2. Secondary Outcome

Title	Number of Participants With Hematologic Response at Week 24
Description	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.
Time Frame	Week 24 Follow-up Visit

Outcome Measure Data

Analysis Population Description

FAS included participants who were assigned to investigational product and who took at least 1 dose of investigational product.

Arm/Group Title	PF-06462700
Arm/Group Description	Participants aged 2 years or >2 years with moderate and above severity aplastic anemia received PF-06462700 at a dose of 40 mg/kg/day, IV for 4 days. Participants after treatment were followed up for 24 weeks.
Measure Participants	3
Effective	2 66.7%
Not Effective	1 33.3%

3. Secondary Outcome

Title	Absolute Neutrophil Count at Day 4, Weeks 1, 2, 4, 6, 8, 10, 12, 24
Time Frame	Treatment: Day 4; Follow-up: Week 1, 2, 4, 6, 8, 10, 12, 24

Outcome Measure Data

Analysis Population Description

FAS included participants who were assigned to investigational product and who took at least 1 dose of investigational product.

Arm/Group Title	PF-06462700
Arm/Group Description	Participants aged 2 years or >2 years with moderate and above severity aplastic anemia received PF-06462700 at a dose of 40 mg/kg/day, IV for 4 days. Participants after treatment were followed up for 24 weeks.
Measure Participants	3
Number [Neutrophil cells per microliter]	NA

4. Secondary Outcome

Title	Platelet Count at Day 4, Weeks 1, 2, 4, 6, 8, 10, 12, 24
Time Frame	Treatment: Day 4; Follow-up: Week 1, 2, 4, 6, 8, 10, 12, 24

Outcome Measure Data

Analysis Population Description

FAS included participants who were assigned to investigational product and who took at least 1 dose of investigational product.

Arm/Group Title	PF-06462700
Arm/Group Description	Participants aged 2 years or >2 years with moderate and above severity aplastic anemia received PF-06462700 at a dose of 40 mg/kg/day, IV for 4 days. Participants after treatment were followed up for 24 weeks.
Measure Participants	3
Number [Platelet cells per microliter]	NA

5. Secondary Outcome

Title	Reticulocyte Count at Day 4, Weeks 1, 2, 4, 6, 8, 10, 12, 24
Time Frame	Treatment: Day 4; Follow-up: Week 1, 2, 4, 6, 8, 10, 12, 24

Outcome Measure Data

Analysis Population Description

FAS included participants who were assigned to investigational product and who took at least 1 dose of investigational product.

Arm/Group Title	PF-06462700
Arm/Group Description	Participants aged 2 years or >2 years with moderate and above severity aplastic anemia received PF-06462700 at a dose of 40 mg/kg/day, IV for 4 days. Participants after treatment were followed up for 24 weeks.
Measure Participants	3
Number [Reticulocyte cells per microliter]	NA

6. Secondary Outcome

Title	Number of Participants Who Survived During the Study
Description	In this outcome measure, number of participants who survived during the study were observed.
Time Frame	Screening (up to 28 days prior to Day 1 of treatment) up to 24 weeks of follow-up (approximately up to 28 weeks)

Outcome Measure Data

Analysis Population Description

FAS included participants who were assigned to investigational product and who took at least 1 dose of investigational product.

Arm/Group Title	PF-06462700
Arm/Group Description	Participants aged 2 years or >2 years with moderate and above severity aplastic anemia received PF-06462700 at a dose of 40 mg/kg/day, IV for 4 days. Participants after treatment were followed up for 24 weeks.
Measure Participants	3
Count of Participants [Participants]	3 100%

7. Secondary Outcome

Title	Number of Participants With Transfusion Independence at Weeks 12 and 24
Description	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).
Time Frame	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)

Outcome Measure Data

Analysis Population Description

FAS included participants who were assigned to investigational product and who took at least 1 dose of investigational product.

Arm/Group Title	PF-06462700
Arm/Group Description	Participants aged 2 years or >2 years with moderate and above severity aplastic anemia received PF-06462700 at a dose of 40 mg/kg/day, IV for 4 days. Participants after treatment were followed up for 24 weeks.
Measure Participants	3
Week 12 Transfusion Independence	0 0%
Week 24 Transfusion Independence	2 66.7%

Adverse Events

Time Frame	Screening up to 24 weeks of follow-up (approximately up to 28 weeks)
Arm/Group Title	PF-06462700
Arm/Group Description	Participants aged 2 years or >2 years with moderate and above severity aplastic anemia received PF-06462700 at a dose of 40 mg/kg/day, IV for 4 days. Participants after treatment were followed up for 24 weeks.
All Cause Mortality
	PF-06462700
	Affected / at Risk (%)	# Events
Total	0/3 (0%)
Serious Adverse Events
	PF-06462700
	Affected / at Risk (%)	# Events
Total	0/3 (0%)
Other (Not Including Serious) Adverse Events
	PF-06462700
	Affected / at Risk (%)	# Events
Total	3/3 (100%)
Endocrine disorders
Adrenal insufficiency	1/3 (33.3%)
Gastrointestinal disorders
Abdominal pain	2/3 (66.7%)
Constipation	1/3 (33.3%)
Dental caries	1/3 (33.3%)
Gastrointestinal disorder	1/3 (33.3%)
Gastrooesophageal reflux disease	1/3 (33.3%)
Nausea	2/3 (66.7%)
Proctalgia	1/3 (33.3%)
General disorders
Feeling abnormal	1/3 (33.3%)
Infusion site extravasation	1/3 (33.3%)
Oedema	1/3 (33.3%)
Immune system disorders
Hypogammaglobulinaemia	1/3 (33.3%)
Serum sickness	1/3 (33.3%)
Infections and infestations
Cytomegalovirus infection	1/3 (33.3%)
Cytomegalovirus viraemia	1/3 (33.3%)
Staphylococcal infection	1/3 (33.3%)
Investigations
Alanine aminotransferase increased	1/3 (33.3%)
Aspartate aminotransferase increased	1/3 (33.3%)
Blood bilirubin increased	1/3 (33.3%)
Blood creatinine increased	1/3 (33.3%)
Blood lactate dehydrogenase increased	1/3 (33.3%)
C-reactive protein increased	1/3 (33.3%)
Gamma-glutamyltransferase increased	1/3 (33.3%)
Lymphocyte count decreased	1/3 (33.3%)
Oxygen saturation abnormal	1/3 (33.3%)
White blood cell count decreased	1/3 (33.3%)
Metabolism and nutrition disorders
Hyperglycaemia	2/3 (66.7%)
Hypokalaemia	1/3 (33.3%)
Nervous system disorders
Tremor	1/3 (33.3%)
Psychiatric disorders
Insomnia	1/3 (33.3%)
Renal and urinary disorders
Proteinuria	1/3 (33.3%)
Renal impairment	1/3 (33.3%)
Reproductive system and breast disorders
Genital haemorrhage	1/3 (33.3%)
Respiratory, thoracic and mediastinal disorders
Productive cough	1/3 (33.3%)
Skin and subcutaneous tissue disorders
Acne	1/3 (33.3%)
Dry skin	1/3 (33.3%)
Nail bed inflammation	1/3 (33.3%)
Vascular disorders
Hypertension	2/3 (66.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from the study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.