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Efficacy, Safety and Tolerability of Denosumab in the Treatment of Rheumatoid Arthritis

Phase 2
Completed
Conditions
Rheumatoid Arthritis
Interventions
Drug: placebo
Registration Number
NCT00095498
Lead Sponsor
Amgen
Brief Summary

This study will determine the efficacy, safety, and tolerability of denosumab (AMG 162) in the treatment of Rheumatoid Arthritis (RA).

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
227
Inclusion Criteria
  • Diagnosis of RA.
  • All subjects will be required to have been taking a stable dose of methotrexate.
  • Active RA at screening defined as greater than or equal to 6 swollen joints.
  • The presence of erosive disease
Exclusion Criteria
  • Received any biologic agent (e.g., Enbrel®, Remicade®, Humira®, Kineret®) or Arava® within 8 weeks before randomization; past use of these agents is allowed.
  • Steroid use greater than 15 mg/day.
  • Scheduled for surgery or joint replacement in the hands, wrists or feet.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboplaceboParticipants received placebo subcutaneous injections on Day 1 and at Month 6.
Denosumab 180 mgdenosumabParticipants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.
Denosumab 60 mgdenosumabParticipants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.
Primary Outcome Measures
NameTimeMethod
Change From Baseline in Rheumatoid Arthritis Erosion Score Measured From MRI Assessments (RA-MRI ES) at Month 6Baseline, Month 6

Fifteen sites in each wrist and 10 sites in each hand were assessed by a blinded and independent reader. Each site was scored from 0 to 10 (in accordance with the European League Against Rheumatism \[EULAR\]-Outcome Measures in Rheumatology Clinical Trials convention), with each unit increment representing 10% incremental loss of the peripheral 1 cm of articular bone. The Erosion Score is a sum of erosion scores from 50 joint sites in both hands/wrists and ranges from 0 (normal, no erosion) to 500 (worst possible erosion).

Secondary Outcome Measures
NameTimeMethod
Change From Baseline in Total Protein at Month 12Baseline, month 12

Laboratory chemistry total protein

Change From Baseline in Bicarbonate at Month 3baseline, month 3

Laboratory chemistry bicarbonate

Change From Baseline in Bicarbonate at Month 12Baseline, Month 12

Laboratory chemistry bicarbonate

Change From Baseline in Total Bilirubin at Month 6Baseline, month 6

Laboratory chemistry total bilirubin

Change From Baseline in Alanine Amino Transferase at Month 3Baseline, month 3

Laboratory Chemistry alanine amino transferase

Change From Baseline in Radiographic Joint Space Narrowing Score at Month 6Baseline, Month 6

Joint Space Narrowing (JSN) Score summarizes the severity of JSN in 30 joints of the hands and 12 joints of the feet obtained from radiographs of the hands and feet and assessed by 2 independent readers. Assessment of JSN for each hand (15 joints per hand) and foot (6 joints per foot), including subluxation, was scored from 0 (normal JSN) to 4 (complete loss of joint space, bony ankylosis, or luxation), with a maximum JSN score (indicating worst joint space narrowing) of 168.

Percent Change From Baseline in Femoral Neck Bone Mineral Density at Month 6Baseline, Month 6

Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from baseline to Month 6 calculated using ((Month 6 value - baseline value) / baseline value ) x 100. Least squares means based on repeated measures model adjusting for treatment, visit, baseline value, and strata (4 strata from the combination of baseline use of steroid and previous use of biologic).

Percent Change From Baseline in Total Hip Bone Mineral Density at Month 12Baseline, Month 12

Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from baseline to Month 12 calculated using ((Month 12 value - baseline value) / baseline value ) x 100. Least squares means based on repeated measures model adjusting for treatment, visit, baseline value, and strata (4 strata from the combination of baseline use of steroid and previous use of biologic).

Percent Change From Baseline in Serum CTX at Month 12Baseline, Month 12

Percent change from Baseline to Month 12 in serum C-Telopeptide (CTX) Type I calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.

Percent Change From Baseline in Urine Type II C-Tx /Creatinine at Month 12Baseline, Month 12

Percent change from baseline to Month 12 in urine Type II collagen C-Telopeptide (CTX)/Creatinine calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.

Number of Participants With Anti-Denosumab Binding Antibody and Neutralizing AntibodyBaseline to Month 12

Serum from participants testing positive for anti-denosumab binding antibodies was tested in a cell-based bioassay for neutralizing activity against denosumab.

Change From Baseline in Albumin at Month 6Baseline, month 6

Laboratory chemistry albumin

Change From Baseline in Albumin at Month 12Baseline, month 12

Laboratory chemistry albumin

Change From Baseline in Blood Urea Nitrogen at Month 12baseline, month 12

Laboratory chemistry blood urea nitrogen

Change From Baseline in Alkaline Phosphatase at Month 3baseline, month 3

Laboratory chemisrty alkaline phosphatase

Change From Baseline in Total Bilirubin at Month 1baseline, month 1

Laboratory chemistry total bilirubin

Change From Baseline in Blood Urea Nitrogen at Month 3Baseline, month 3

Laboratory chemistry blood urea nitrogen

Change From Baseline in Radiographic Joint Space Narrowing Score at Month 12Baseline, Month 12

Joint Space Narrowing (JSN) Score summarizes the severity of JSN in 30 joints of the hands and 12 joints of the feet obtained from radiographs of the hands and feet and assessed by 2 independent readers. Assessment of JSN for each hand (15 joints per hand) and foot (6 joints per foot), including subluxation, was scored from 0 (normal JSN) to 4 (complete loss of joint space, bony ankylosis, or luxation), with a maximum JSN score (indicating worst joint space narrowing) of 168.

Percent Change From Baseline in Procollagen 1 N-terminal Peptide (P1NP) at Month 3Baseline, Month 3

Percent change from baseline to Month 3 in procollagen 1 N-terminal peptide (P1NP) calculated using ((Month 3 value - Baseline value) / Baseline value ) x 100.

Change From Baseline in Albumin at Month 3Baseline, month 3

Laboratory chemistry albumin

Change From Baseline in Bicarbonate at Month 1baseline, month 1

Laboratory chemistry bicarbonate

Change From Baseline in Radiographic Erosion Score at Month 12Baseline, Month 12

The joint erosion score is a summary of erosion severity in 32 joints of the hands and 12 joints in the feet, obtained from radiographs of the hands and feet and assessed by 2 independent readers. Each joint was scored, according to the surface area involved, from 0 (no erosion) to 5 (extensive loss of bone from more than one half of the articulating bone). Because each side of a foot joint was graded on this scale, the maximum erosion score for a foot joint was 10 and the maximal erosion score was 280.

Change From Baseline in Radiographic Erosion Score at Month 6Baseline, Month 6

The joint erosion score is a summary of erosion severity in 32 joints of the hands and 12 joints in the feet, obtained from radiographs of the hands and feet and assessed by 2 independent readers. Each joint was scored, according to the surface area involved, from 0 (no erosion) to 5 (extensive loss of bone from more than one half of the articulating bone). Because each side of a foot joint was graded on this scale, the maximum erosion score for a foot joint was 10 and the maximal erosion score was 280.

Percent Change From Baseline in Lumbar Spine Bone Mineral Density at Month 12Baseline, Month 12

Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from baseline to Month 12 calculated using ((Month 12 value - baseline value) / baseline value ) x 100. Least squares means based on repeated measures model adjusting for treatment, visit, baseline value, and strata (4 strata from the combination of baseline use of steroid and previous use of biologic).

Percent Change From Baseline in Total Hip Bone Mineral Density at Month 1Baseline, Month 1

Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from baseline to Month 1 calculated using ((Month 1 value - baseline value) / baseline value ) x 100. Least squares means based on repeated measures model adjusting for treatment, visit, baseline value, and strata (4 strata from the combination of baseline use of steroid and previous use of biologic).

Percent Change From Baseline in Serum CTX at Month 6Baseline, Month 6

Percent change from baseline to Month 6 in serum Collagen C-Telopeptide (CTX) Type I calculated using ((Month 6 value - Baseline value) / Baseline value ) x 100.

Percent Change From Baseline in P1NP at Month 6Baseline, Month 6

Percent change from baseline to Month 6 in procollagen 1 N-terminal peptide (P1NP) calculated using ((Month 6 value - Baseline value) / Baseline value ) x 100.

Number of Participants With Anti-Denosumab Binding AntibodiesAssessed at Baseline and at Months 1, 3, 6 and 12.

Serum from participants was tested for antibodies to denosumab by immuoassay at months 1, 3, 6 and 12. The number of participants with anti-denosumab antibodies at any assessment is reported.

Change From Baseline in Albumin at Month 1Baseline, month 1

Laboratory Chemistry Albumin

Change From Baseline in Radiographic Total Modified Sharp Score (TSS) at Month 12Baseline, Month 12

TSS is the sum of erosion and joint space narrowing scores obtained from radiographs of the hands and feet, assessed by 2 independent readers. The joint erosion score is a summary of erosion severity in 32 joints of the hands and 12 joints in the feet. Each joint was scored, according to the surface area involved, from 0 (no erosion) to 5 (extensive loss of bone from more than one half of the articulating bone). Because each side of a foot joint was graded on this scale, the maximum erosion score for a foot joint was 10 and the maximal erosion score was 280. Joint Space Narrowing (JSN) Score summarizes the severity of JSN in 30 joints of the hands and 12 joints of the feet. Assessment of JSN for each hand (15 joints per hand) and foot (6 joints per foot), including subluxation, was scored from 0 (normal JSN) to 4 (complete loss of joint space, bony ankylosis, or luxation), with a maximum JSN score of 168. The TSS ranged from 0 (normal) to 448 (worst).

Change From Baseline in Radiographic Total Modified Sharp Score (TSS) at Month 6Baseline, Month 6

TSS is the sum of erosion and joint space narrowing scores obtained from radiographs of the hands and feet, assessed by 2 independent readers. The joint erosion score is a summary of erosion severity in 32 joints of the hands and 12 joints in the feet. Each joint was scored, according to the surface area involved, from 0 (no erosion) to 5 (extensive loss of bone from more than one half of the articulating bone). Because each side of a foot joint was graded on this scale, the maximum erosion score for a foot joint was 10 and the maximal erosion score was 280. Joint Space Narrowing (JSN) Score summarizes the severity of JSN in 30 joints of the hands and 12 joints of the feet. Assessment of JSN for each hand (15 joints per hand) and foot (6 joints per foot), including subluxation, was scored from 0 (normal JSN) to 4 (complete loss of joint space, bony ankylosis, or luxation), with a maximum JSN score of 168. The TSS ranged from 0 (normal) to 448 (worst).

Percent Change From Baseline in Lumbar Spine Bone Mineral Density at Month 1Baseline, Month 1

Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from baseline to Month 1 calculated using ((month 1 value - baseline value) / baseline value ) x 100. Least squares means are based on a repeated measures model adjusting for treatment, visit, baseline value, and strata (4 strata from the combination of baseline use of steroid and previous use of biologic).

Percent Change From Baseline in Lumbar Spine Bone Mineral Density at Month 6Baseline, month 6

Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from baseline to month 6 calculated using ((month 6 value - baseline value) / baseline value ) x 100. Least squares means are based on a repeated measures model adjusting for treatment, visit, baseline value, and strata (4 strata from the combination of baseline use of steroid and previous use of biologic).

Percent Change From Baseline in Femoral Neck Bone Mineral Density at Month 1Baseline, Month 1

Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from baseline to Month 1 calculated using ((Month 1 value - baseline value) / baseline value ) x 100.

Least squares means based on repeated measures model adjusting for treatment, visit, baseline value, and strata (4 strata from the combination of baseline use of steroid and previous use of biologic).

Change From Baseline in Blood Urea Nitrogen at Month 1Baseline, month 1

Laboratory chemistry blood urea nitrogen

Percent Change From Baseline in Femoral Neck Bone Mineral Density at Month 12Baseline, Month 12

Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from baseline to Month 12 calculated using ((Month 12 value - baseline value) / baseline value ) x 100. Least squares means based on repeated measures model adjusting for treatment, visit, baseline value, and strata (4 strata from the combination of baseline use of steroid and previous use of biologic).

Percent Change From Baseline in Total Hip Bone Mineral Density at Month 6Baseline, Month 6

Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from baseline to Month 6 calculated using ((Month 6 value - baseline value) / baseline value ) x 100. Least squares means based on repeated measures model adjusting for treatment, visit, baseline value, and strata (4 strata from the combination of baseline use of steroid and previous use of biologic).

Percent Change From Baseline in Serum Collagen C-Telopeptide (CTX) at Month 3Baseline, Month 3

Percent change from baseline to Month 3 in serum Collagen C-Telopeptide (CTX) Type I calculated using ((Month 3 value - Baseline value) / Baseline value ) x 100.

Percent Change From Baseline in P1NP at Month 12Baseline, Month 12

Percent change from baseline to Month 12 in procollagen 1 N-terminal peptide (P1NP) calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.

Percent Change From Baseline in Urine Type II Collagen C-telopeptide (C-Tx) /Creatinine at Month 3Baseline, Month 3

Percent change from baseline to Month 3 in urine Type II collagen C-Telopeptide (CTX)/Creatinine calculated using ((Month 3 value - Baseline value) / Baseline value ) x 100.

Percent Change From Baseline in Urine Type II C-Tx /Creatinine at Month 6Baseline, Month 6

Percent change from baseline to Month 6 in urine Type II collagen C-Telopeptide (CTX)/Creatinine calculated using ((Month 6 value - Baseline value) / Baseline value ) x 100.

Change From Baseline in Alkaline Phosphatase at Month 6baseline, month 6

Laboratory chemistry alkaline phosphatase

Change From Baseline in Alkaline Phosphatase at Month 12baseine, month 12

Laboratory chemistry alkaline phosphatase

Change From Baseline in Total Bilirubin at Month 3Baseline, month 3

Laboratory chemistry total bilirubin

Change From Baseline in Total Bilirubin at Month 12Baseline, month 12

Laboratory chemistry total bilirubin

Change From Baseline in Alkaline Phosphatase at Month 1Baseline, month 1

Laboratory chemistry alkaline phoshatatse

Change From Baseline in Bicarbonate at Month 6Baseline, month 6

Laboratory chemistry bicarbonate

Change From Baseline in Blood Urea Nitrogen at Month 6Baseline, month 6

Laboratory chemistry blood urea nitrogen

Change From Baseline in Calcium at Month 6baseline, month 6

Laboratory chemistry calcium

Change From Baseline in Calcium (Corrected) at Month 3baseline, month 3

Laboratory chemistry albumin-adjusted calcium

Change From Baseline in Calcium (Corrected) at Month 12Baselien, Month 12

Laboratory chemistry albumin-adjusted calcium

Change From Baseline in Chloride at Month 12Baseline, month 12

Laboratory chemistry chloride

Change From Baseline in Glucose at Month 1Baseline, month 1

Laboratory chemistry glucose

Change From Baseline in Potassium at Month 6Baseline, month 6

Laboratory chemistry potassium

Change From Baseline in Gamma-Glutamyl Transferase at Month 12Baseline, month 12

Laboratory chemistry gamma-glutamyl transferase

Change From Baseline in Glucose at Month 3Baseline, month 3

Laboratory chemistry glucose

Change From Baseline in Chloride at Month 1baseline, month 1

Laboratory chemistry chloride

Change From Baseline in Creatinine at Month 6Baseline, month 6

Laboratory chemistry creatinine

Change From Baseline in Creatinine at Month 12Baseline, month 12

Laboratory chemistry creatinine

Change From Baseline in Magnesium at Month 3Baseline, month 3

Laboratory chemistry magnesium

Change From Baseline in Magnesium at Month 6Baseline, month 6

Laboratory chemistry magnesium

Change From Baseline in Sodium at Month 6Baseline, month 6

Laboratory chemistry sodium

Change From Baseline in Calcium at Month 1baseline. month 1

Laboratory chemistry calcium

Change From Baseline in Calcium (Corrected) at Month 6Baseline, Month 6

Laboratory chemistry albumin-adjusted calcium

Change From Baseline in Gamma-Glutamyl Transferase at Month 6Baseline, month 6

Laboratory chemistry gamma-glutamyl transferase

Change From Baseline in Potassium at Month 1Baseline, month 1

Laboratory chemistry potassium

Change From Baseline in Magnesium at Month 12Baseline, month 12

Laboratory chemistry magnesium

Change From Baseline in Sodium at Month 1Baseline, month 1

Laboratory chemistry sodium

Change From Baseline in Phosphorus at Month 6Baseline, month 6

Laboratory chemistry phosphorus

Change From Baseline in Lymphocytes at Month 6Baseline, month 6

Laboratory hematology lymphocytes

Change From Baseline in Calcium at Month 3Baseline, month 3

Laboratory chemistry calcium

Change From Baseline in Chloride at Month 3Baseline, month 3

Laboratory chemistry chloride

Change From Baseline in Creatinine at Month 3Baseline, month 3

Laboratory chemistry creatinine

Change From Baseline in Gamma-Glutamyl Transferase at Month 1Baseline, month 1

Laboratory chemistry gamma-glutamyl transferase

Change From Baseline in Glucose at Month 6Baseline, month 6

Laboratory chemistry glucose

Change From Baseline in Magnesium at Month 1Baseline, month 1

Laboratory chemistry magnesium

Change From Baseline in Total Protein at Month 3Baseline, month 3

Laboratory chemistry total protein

Change From Baseline in Total Protein at Month 6Baseline, month 6

Laboratory chemistry total protein

Change From Baseline in Alanine Amino Transferase at Month 1Baseline, month 1

Laboratory chemistry alanine amino transferase

Change From Baseline in Alanine Amino Transferase at Month 6Baseline, month 6

Laboratory chemistry alanine amino transferase

Change From Baseline in Eosinophils at Month 6Baseline, month 6

Laboratory hematology eosinophils

Change From Baseline in Calcium at Month 12Baseline, month 12

Laboratory chemistry calcium

Change From Baseline in Calcium (Corrected) at Month 1Baseline, month 1

Laboratory chemistry albumin-adjusted calcium

Change From Baseline in Chloride at Month 6Baseline, month 6

Laboratory chemistry chloride

Change From Baseline in Creatinine at Month 1Baseline, month 1

Laboratory chemistry creatinine

Change From Baseline in Gamma-Glutamyl Transferase at Month 3Baseline, month 3

Laboratory chemistry gamma-glutamyl transferase

Change From Baseline in Glucose at Month 12baseline, month 12

Laboratory chemistry glucose

Change From Baseline in Potassium at Month 12Baseline, month 12

Laboratory chemistry potassium

Change From Baseline in Sodium at Month 3Baseline, Month 3

Change From Baseline in Sodium at Month 3

Change From Baseline in Phosphorus at Month 12Baseline, month 12

Change From Baseline in Phosphorus at Month 12

Change From Baseline in Aspartate Amino Transferase at Month 12Baseline, month 12

Laboratory chemistry aspartate amino transferase

Change From Baseline in White Blood Cells at Month 3Baseline, month 3

Laboratpry hematology white blood cells

Change From Baseline in Potassium at Month 3Baseline, month 3

Laboratory chemistry potassium

Change From Baseline in Sodium at Month 12Baseline, month 12

Laboratory chemistry sodium

Change From Baseline in Phosphorus at Month 1Baseline, month 1

Laboratory chemistry phosphorus

Change From Baseline in Phosphorus at Month 3Baseline, month 3

Laboratory chemistry phosphorus

Change From Baseline in Aspartate Amino TransferaseBaseline, month 6

Laboratory chemistry aspartate amino transferase

Change From Baseline in Basophils at Month 3Baseline, month 3

Laboratory hematology basophils

Change From Baseline in Basophils at Month 12Baseline, month 12

Laboratory hematology basophils

Change From Baseline in Eosinophils at Month 12Baseline, month 12

Laboratory hematology eosinophils

Change From Baseline in Hematocrit at Month 3Baseline, month 3

Laboratory hematology hematocrit

Change From Baseline in Hematocrit at Month 6Baseline, month 6

Laboratory hematology hematocrit

Change From Baseline in Lymphocytes at Month 3Baseline, month 3

Laboratory hematology lymphocytes

Change From Baseline in Monocytes at Month 12Baseline, month 12

Laboratory hematology monocytes

Change From Baseline in Total Neutrophils at Month 1Baseline, month 1

Laboratory hematology total neutrophils

Change From Baseline in Platelets at Month 6Baseline, month 6

Laboratory hematology platelets

Change From Baseline in Red Blood Cells at Month 6Baseline, month 6

Laboratory hematology red blood cells

Change From Baseline in Total Protein at Month 1Baseline, month 1

Laboratory chemistry total protein

Change From Baseline in Aspartate Amino Transferase at Month 1Baseline, month 1

Laboratory chemistry aspartate amino transferase

Change From Baseline in Aspartate Amino Transferase at Month 3Baseline, month 3

Laboratory chemistry aspartate amino transferase

Change From Baseline in Alanine Amino Transferase at Month 12Baseline, month 12

Laboratory chemistry alanine amino transferase

Change From Baseline in Basophils at Month 1baseline, month 1

Laboratory hematology basophils

Change From Baseline in Basophils at Month 6Baseline, month 6

Laboratory hematology basophils

Change From Baseline in Hematocrit at Month 1Baseline, month 1

Laboratory hematology hematocrit

Change From Baseline in Hemoglobin at Month 3Baseline, month 3

Laboratory hematology hemoglobin

Change From Baseline in Lymphocytes at Month 12Baseline, month 12

Laboratory hematology lymphocytes

Change From Baseline in Monocytes at Month 1Baseline, month 1

Laboratory hematology monocytes

Change From Baseline in Monocytes at Month 6Baseline, month 6

Laboratory hematology monocytes

Change From Baseline in Platelets at Month 3Baseline, month 3

Laboratory hematology platelets

Change From Baseline in Eosinophils at Month 1Baseline, month 1

Laboratory hematology eosinophils

Change From Baseline in Eosinophils at Month 3Baseline, month 3

Laboratory hematology eosinophils

Change From Baseline in Hematocrit at Month 12Baseline, month 12

Laboratory hematology hematocrit

Change From Baseline in Hemoglobin at Month 1Baseline, month 1

Laboratory hematology hemoglobin

Change From Baseline in Hemoglobin at Month 12Baseline, month 12

Laboratory hematology hemoglobin

Change From Baseline in Total Neutrophils at Month 6Baseline, month 6

Laboratory hematology total neutrophils

Change From Baseline in Red Blood Cells at Month 12Baseline, month 12

Laboratory hematology red blood cells

Change From Baseline in White Blood Cells at Month 1Baseline, month 1

Laboratory hematology white blood cells

Number of Participants With Laboratory Common Terminology Criteria for Adverse Events (CTCAE) Grade Greater or Equal to 3Month 1, month 3, month 6, month 12

Participants with laboratory toxicity of grade 3 or 4, graded according to the Common Terminology Criteria for Adverse Events, version 3.0, on the following general guideline:

Grade 1 - Mild AE; Grade 2 - Moderate AE; Grade 3 - Severe AE; Grade 4 - Life-threatening or disabling AE; Grade 5 - Death related to AE.

Change From Baseline in Hemoglobin at Month 6Baseline, month 6

Laboratory hematology hemoglobin

Change From Baseline in Lymphocytes at Month 1Baseline, month 1

Laboratory hematology lymphocytes

Change From Baseline in Monocytes at Month 3Baseline, month 3

Laboratory hematology monocytes

Change From Baseline in Total Neutrophils at Month 3Baseline, month 3

Laboratory hematology total neutrophils

Change From Baseline in Total Neutrophils at Month 12Baseline, month 12

Laboratory hematology total neutrophils

Change From Baseline in Platelets at Month 1Baseline, month 1

Laboratory hematology platelets

Change From Baseline in White Blood Cells at Month 6Baseline, month 6

Laboratory hematology white blood cells

Change From Baseline in White Blood Cells at Month 12Baseline, month 12

Laboratory hematology white blood cells

Change From Baseline in Platelets at Month 12Baseline, month 12

Laboratory hematology platelets

Change From Baseline in Red Blood Cells at Month 1Baseline, month 1

Laboratory hematology red blood cells

Change From Baseline in Red Blood Cells at Month 3Baseline, month 3

Laboratory hematology red blood cells

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