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

A Phase 2 study testing denosumab in people with Rheumatoid Arthritis, run by Amgen.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

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

Who is it for?: Ages 18 years and older
Conditions the study is for: Rheumatoid Arthritis
What is being tested?: denosumab
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 227 participants
Where: No sites listed yet
Study dates: 11 Aug 2004to 1 Apr 2007
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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.

About this study

Official title: A Randomized, Double-blind, Placebo-controlled, Multi-dose Phase 2 Study to Determine the Efficacy, Safety and Tolerability of Denosumab in the Treatment of Rheumatoid Arthritis

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

Conditions: Rheumatoid Arthritis
Being tested: placebo, denosumab
Keywords: arthritis, joint pain, Methotrexate
Medical subject headings: Arthritis, Rheumatoid, Arthritis, Arthralgia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

placeboDrug
placebo subcutaneous injection
denosumabDrug
Also called AMG 162
For subcutaneous injection

Study groups in NCT00095498
Study group	Role	What they receive
Denosumab 180 mg	Experimental	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6. Receives: Drug: denosumab
Denosumab 60 mg	Experimental	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6. Receives: Drug: denosumab
Placebo	Placebo comparator	Participants received placebo subcutaneous injections on Day 1 and at Month 6. Receives: Drug: placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Change From Baseline in Rheumatoid Arthritis Erosion Score Measured From MRI Assessments (RA-MRI ES) at 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).
Measured: Baseline, Month 6

Secondary outcomes (139)

Change From Baseline in Radiographic Total Modified Sharp Score (TSS) at 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).
Measured: Baseline, Month 12
Change From Baseline in Radiographic Total Modified Sharp Score (TSS) at 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).
Measured: Baseline, Month 6
Change From Baseline in Radiographic Erosion Score at 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.
Measured: Baseline, Month 12
Change From Baseline in Radiographic Erosion Score at 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.
Measured: Baseline, Month 6
Change From Baseline in Radiographic Joint Space Narrowing Score at 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.
Measured: Baseline, Month 12
Change From Baseline in Radiographic Joint Space Narrowing Score at 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.
Measured: Baseline, Month 6
Percent Change From Baseline in Lumbar Spine Bone Mineral Density at 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).
Measured: Baseline, Month 1
Percent Change From Baseline in Lumbar Spine Bone Mineral Density at 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).
Measured: Baseline, month 6
Percent Change From Baseline in Lumbar Spine Bone Mineral Density at 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).
Measured: Baseline, Month 12
Percent Change From Baseline in Femoral Neck Bone Mineral Density at 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).
Measured: Baseline, Month 1
Percent Change From Baseline in Femoral Neck Bone Mineral Density at 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).
Measured: Baseline, Month 6
Percent Change From Baseline in Femoral Neck Bone Mineral Density at 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).
Measured: Baseline, Month 12
Percent Change From Baseline in Total Hip Bone Mineral Density at 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).
Measured: Baseline, Month 1
Percent Change From Baseline in Total Hip Bone Mineral Density at 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).
Measured: Baseline, Month 6
Percent Change From Baseline in Total Hip Bone Mineral Density at 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).
Measured: Baseline, Month 12
Percent Change From Baseline in Serum Collagen C-Telopeptide (CTX) at 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.
Measured: Baseline, Month 3
Percent Change From Baseline in Serum CTX at 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.
Measured: Baseline, Month 6
Percent Change From Baseline in Serum CTX at 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.
Measured: Baseline, Month 12
Percent Change From Baseline in Procollagen 1 N-terminal Peptide (P1NP) at 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.
Measured: Baseline, Month 3
Percent Change From Baseline in P1NP at 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.
Measured: Baseline, Month 6
Percent Change From Baseline in P1NP at 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.
Measured: Baseline, Month 12
Percent Change From Baseline in Urine Type II Collagen C-telopeptide (C-Tx) /Creatinine at 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.
Measured: Baseline, Month 3
Percent Change From Baseline in Urine Type II C-Tx /Creatinine at 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.
Measured: Baseline, Month 6
Percent Change From Baseline in Urine Type II C-Tx /Creatinine at 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.
Measured: Baseline, Month 12
Number of Participants With Anti-Denosumab Binding Antibodies
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.
Measured: Assessed at Baseline and at Months 1, 3, 6 and 12.
Number of Participants With Anti-Denosumab Binding Antibody and Neutralizing Antibody
Serum from participants testing positive for anti-denosumab binding antibodies was tested in a cell-based bioassay for neutralizing activity against denosumab.
Measured: Baseline to Month 12
Change From Baseline in Albumin at Month 1
Laboratory Chemistry Albumin
Measured: Baseline, month 1
Change From Baseline in Albumin at Month 3
Laboratory chemistry albumin
Measured: Baseline, month 3
Change From Baseline in Albumin at Month 6
Laboratory chemistry albumin
Measured: Baseline, month 6
Change From Baseline in Albumin at Month 12
Laboratory chemistry albumin
Measured: Baseline, month 12
Change From Baseline in Alkaline Phosphatase at Month 1
Laboratory chemistry alkaline phoshatatse
Measured: Baseline, month 1
Change From Baseline in Alkaline Phosphatase at Month 3
Laboratory chemisrty alkaline phosphatase
Measured: baseline, month 3
Change From Baseline in Alkaline Phosphatase at Month 6
Laboratory chemistry alkaline phosphatase
Measured: baseline, month 6
Change From Baseline in Alkaline Phosphatase at Month 12
Laboratory chemistry alkaline phosphatase
Measured: baseine, month 12
Change From Baseline in Bicarbonate at Month 1
Laboratory chemistry bicarbonate
Measured: baseline, month 1
Change From Baseline in Bicarbonate at Month 3
Laboratory chemistry bicarbonate
Measured: baseline, month 3
Change From Baseline in Bicarbonate at Month 6
Laboratory chemistry bicarbonate
Measured: Baseline, month 6
Change From Baseline in Bicarbonate at Month 12
Laboratory chemistry bicarbonate
Measured: Baseline, Month 12
Change From Baseline in Total Bilirubin at Month 1
Laboratory chemistry total bilirubin
Measured: baseline, month 1
Change From Baseline in Total Bilirubin at Month 3
Laboratory chemistry total bilirubin
Measured: Baseline, month 3
Change From Baseline in Total Bilirubin at Month 6
Laboratory chemistry total bilirubin
Measured: Baseline, month 6
Change From Baseline in Total Bilirubin at Month 12
Laboratory chemistry total bilirubin
Measured: Baseline, month 12
Change From Baseline in Blood Urea Nitrogen at Month 1
Laboratory chemistry blood urea nitrogen
Measured: Baseline, month 1
Change From Baseline in Blood Urea Nitrogen at Month 3
Laboratory chemistry blood urea nitrogen
Measured: Baseline, month 3
Change From Baseline in Blood Urea Nitrogen at Month 6
Laboratory chemistry blood urea nitrogen
Measured: Baseline, month 6
Change From Baseline in Blood Urea Nitrogen at Month 12
Laboratory chemistry blood urea nitrogen
Measured: baseline, month 12
Change From Baseline in Calcium at Month 1
Laboratory chemistry calcium
Measured: baseline. month 1
Change From Baseline in Calcium at Month 3
Laboratory chemistry calcium
Measured: Baseline, month 3
Change From Baseline in Calcium at Month 6
Laboratory chemistry calcium
Measured: baseline, month 6
Change From Baseline in Calcium at Month 12
Laboratory chemistry calcium
Measured: Baseline, month 12
Change From Baseline in Calcium (Corrected) at Month 1
Laboratory chemistry albumin-adjusted calcium
Measured: Baseline, month 1
Change From Baseline in Calcium (Corrected) at Month 3
Laboratory chemistry albumin-adjusted calcium
Measured: baseline, month 3
Change From Baseline in Calcium (Corrected) at Month 6
Laboratory chemistry albumin-adjusted calcium
Measured: Baseline, Month 6
Change From Baseline in Calcium (Corrected) at Month 12
Laboratory chemistry albumin-adjusted calcium
Measured: Baselien, Month 12
Change From Baseline in Chloride at Month 1
Laboratory chemistry chloride
Measured: baseline, month 1
Change From Baseline in Chloride at Month 3
Laboratory chemistry chloride
Measured: Baseline, month 3
Change From Baseline in Chloride at Month 6
Laboratory chemistry chloride
Measured: Baseline, month 6
Change From Baseline in Chloride at Month 12
Laboratory chemistry chloride
Measured: Baseline, month 12
Change From Baseline in Creatinine at Month 1
Laboratory chemistry creatinine
Measured: Baseline, month 1
Change From Baseline in Creatinine at Month 3
Laboratory chemistry creatinine
Measured: Baseline, month 3
Change From Baseline in Creatinine at Month 6
Laboratory chemistry creatinine
Measured: Baseline, month 6
Change From Baseline in Creatinine at Month 12
Laboratory chemistry creatinine
Measured: Baseline, month 12
Change From Baseline in Gamma-Glutamyl Transferase at Month 1
Laboratory chemistry gamma-glutamyl transferase
Measured: Baseline, month 1
Change From Baseline in Gamma-Glutamyl Transferase at Month 3
Laboratory chemistry gamma-glutamyl transferase
Measured: Baseline, month 3
Change From Baseline in Gamma-Glutamyl Transferase at Month 6
Laboratory chemistry gamma-glutamyl transferase
Measured: Baseline, month 6
Change From Baseline in Gamma-Glutamyl Transferase at Month 12
Laboratory chemistry gamma-glutamyl transferase
Measured: Baseline, month 12
Change From Baseline in Glucose at Month 1
Laboratory chemistry glucose
Measured: Baseline, month 1
Change From Baseline in Glucose at Month 3
Laboratory chemistry glucose
Measured: Baseline, month 3
Change From Baseline in Glucose at Month 6
Laboratory chemistry glucose
Measured: Baseline, month 6
Change From Baseline in Glucose at Month 12
Laboratory chemistry glucose
Measured: baseline, month 12
Change From Baseline in Potassium at Month 1
Laboratory chemistry potassium
Measured: Baseline, month 1
Change From Baseline in Potassium at Month 3
Laboratory chemistry potassium
Measured: Baseline, month 3
Change From Baseline in Potassium at Month 6
Laboratory chemistry potassium
Measured: Baseline, month 6
Change From Baseline in Potassium at Month 12
Laboratory chemistry potassium
Measured: Baseline, month 12
Change From Baseline in Magnesium at Month 1
Laboratory chemistry magnesium
Measured: Baseline, month 1
Change From Baseline in Magnesium at Month 3
Laboratory chemistry magnesium
Measured: Baseline, month 3
Change From Baseline in Magnesium at Month 6
Laboratory chemistry magnesium
Measured: Baseline, month 6
Change From Baseline in Magnesium at Month 12
Laboratory chemistry magnesium
Measured: Baseline, month 12
Change From Baseline in Sodium at Month 1
Laboratory chemistry sodium
Measured: Baseline, month 1
Change From Baseline in Sodium at Month 3
Change From Baseline in Sodium at Month 3
Measured: Baseline, Month 3
Change From Baseline in Sodium at Month 6
Laboratory chemistry sodium
Measured: Baseline, month 6
Change From Baseline in Sodium at Month 12
Laboratory chemistry sodium
Measured: Baseline, month 12
Change From Baseline in Phosphorus at Month 1
Laboratory chemistry phosphorus
Measured: Baseline, month 1
Change From Baseline in Phosphorus at Month 3
Laboratory chemistry phosphorus
Measured: Baseline, month 3
Change From Baseline in Phosphorus at Month 6
Laboratory chemistry phosphorus
Measured: Baseline, month 6
Change From Baseline in Phosphorus at Month 12
Change From Baseline in Phosphorus at Month 12
Measured: Baseline, month 12
Change From Baseline in Total Protein at Month 1
Laboratory chemistry total protein
Measured: Baseline, month 1
Change From Baseline in Total Protein at Month 3
Laboratory chemistry total protein
Measured: Baseline, month 3
Change From Baseline in Total Protein at Month 6
Laboratory chemistry total protein
Measured: Baseline, month 6
Change From Baseline in Total Protein at Month 12
Laboratory chemistry total protein
Measured: Baseline, month 12
Change From Baseline in Aspartate Amino Transferase at Month 1
Laboratory chemistry aspartate amino transferase
Measured: Baseline, month 1
Change From Baseline in Aspartate Amino Transferase at Month 3
Laboratory chemistry aspartate amino transferase
Measured: Baseline, month 3
Change From Baseline in Aspartate Amino Transferase
Laboratory chemistry aspartate amino transferase
Measured: Baseline, month 6
Change From Baseline in Aspartate Amino Transferase at Month 12
Laboratory chemistry aspartate amino transferase
Measured: Baseline, month 12
Change From Baseline in Alanine Amino Transferase at Month 1
Laboratory chemistry alanine amino transferase
Measured: Baseline, month 1
Change From Baseline in Alanine Amino Transferase at Month 3
Laboratory Chemistry alanine amino transferase
Measured: Baseline, month 3
Change From Baseline in Alanine Amino Transferase at Month 6
Laboratory chemistry alanine amino transferase
Measured: Baseline, month 6
Change From Baseline in Alanine Amino Transferase at Month 12
Laboratory chemistry alanine amino transferase
Measured: Baseline, month 12
Change From Baseline in Basophils at Month 1
Laboratory hematology basophils
Measured: baseline, month 1
Change From Baseline in Basophils at Month 3
Laboratory hematology basophils
Measured: Baseline, month 3
Change From Baseline in Basophils at Month 6
Laboratory hematology basophils
Measured: Baseline, month 6
Change From Baseline in Basophils at Month 12
Laboratory hematology basophils
Measured: Baseline, month 12
Change From Baseline in Eosinophils at Month 1
Laboratory hematology eosinophils
Measured: Baseline, month 1
Change From Baseline in Eosinophils at Month 3
Laboratory hematology eosinophils
Measured: Baseline, month 3
Change From Baseline in Eosinophils at Month 6
Laboratory hematology eosinophils
Measured: Baseline, month 6
Change From Baseline in Eosinophils at Month 12
Laboratory hematology eosinophils
Measured: Baseline, month 12
Change From Baseline in Hematocrit at Month 1
Laboratory hematology hematocrit
Measured: Baseline, month 1
Change From Baseline in Hematocrit at Month 3
Laboratory hematology hematocrit
Measured: Baseline, month 3
Change From Baseline in Hematocrit at Month 6
Laboratory hematology hematocrit
Measured: Baseline, month 6
Change From Baseline in Hematocrit at Month 12
Laboratory hematology hematocrit
Measured: Baseline, month 12
Change From Baseline in Hemoglobin at Month 1
Laboratory hematology hemoglobin
Measured: Baseline, month 1
Change From Baseline in Hemoglobin at Month 3
Laboratory hematology hemoglobin
Measured: Baseline, month 3
Change From Baseline in Hemoglobin at Month 6
Laboratory hematology hemoglobin
Measured: Baseline, month 6
Change From Baseline in Hemoglobin at Month 12
Laboratory hematology hemoglobin
Measured: Baseline, month 12
Change From Baseline in Lymphocytes at Month 1
Laboratory hematology lymphocytes
Measured: Baseline, month 1
Change From Baseline in Lymphocytes at Month 3
Laboratory hematology lymphocytes
Measured: Baseline, month 3
Change From Baseline in Lymphocytes at Month 6
Laboratory hematology lymphocytes
Measured: Baseline, month 6
Change From Baseline in Lymphocytes at Month 12
Laboratory hematology lymphocytes
Measured: Baseline, month 12
Change From Baseline in Monocytes at Month 1
Laboratory hematology monocytes
Measured: Baseline, month 1
Change From Baseline in Monocytes at Month 3
Laboratory hematology monocytes
Measured: Baseline, month 3
Change From Baseline in Monocytes at Month 6
Laboratory hematology monocytes
Measured: Baseline, month 6
Change From Baseline in Monocytes at Month 12
Laboratory hematology monocytes
Measured: Baseline, month 12
Change From Baseline in Total Neutrophils at Month 1
Laboratory hematology total neutrophils
Measured: Baseline, month 1
Change From Baseline in Total Neutrophils at Month 3
Laboratory hematology total neutrophils
Measured: Baseline, month 3
Change From Baseline in Total Neutrophils at Month 6
Laboratory hematology total neutrophils
Measured: Baseline, month 6
Change From Baseline in Total Neutrophils at Month 12
Laboratory hematology total neutrophils
Measured: Baseline, month 12
Change From Baseline in Platelets at Month 1
Laboratory hematology platelets
Measured: Baseline, month 1
Change From Baseline in Platelets at Month 3
Laboratory hematology platelets
Measured: Baseline, month 3
Change From Baseline in Platelets at Month 6
Laboratory hematology platelets
Measured: Baseline, month 6
Change From Baseline in Platelets at Month 12
Laboratory hematology platelets
Measured: Baseline, month 12
Change From Baseline in Red Blood Cells at Month 1
Laboratory hematology red blood cells
Measured: Baseline, month 1
Change From Baseline in Red Blood Cells at Month 3
Laboratory hematology red blood cells
Measured: Baseline, month 3
Change From Baseline in Red Blood Cells at Month 6
Laboratory hematology red blood cells
Measured: Baseline, month 6
Change From Baseline in Red Blood Cells at Month 12
Laboratory hematology red blood cells
Measured: Baseline, month 12
Change From Baseline in White Blood Cells at Month 1
Laboratory hematology white blood cells
Measured: Baseline, month 1
Change From Baseline in White Blood Cells at Month 3
Laboratpry hematology white blood cells
Measured: Baseline, month 3
Change From Baseline in White Blood Cells at Month 6
Laboratory hematology white blood cells
Measured: Baseline, month 6
Change From Baseline in White Blood Cells at Month 12
Laboratory hematology white blood cells
Measured: Baseline, month 12
Number of Participants With Laboratory Common Terminology Criteria for Adverse Events (CTCAE) Grade Greater or Equal to 3
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.
Measured: Month 1, month 3, month 6, month 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

11 Aug 20041 Apr 2007

First posted8 Nov 2004 (estimated)
Study start11 Aug 2004
Primary completion1 Apr 2007
Study completion1 Apr 2007

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (4)Papers the sponsor has linked to this study.
Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
More trials run by AmgenThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 227 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00095498
Sponsor's protocol ID: 20040144
Status last verified: Oct 2021
First submitted: 5 Nov 2004
Last updated: 25 Oct 2021
Results posted: Yes, on ClinicalTrials.gov

Publications

Cohen SB, Dore RK, Lane NE, Ory PA, Peterfy CG, Sharp JT, van der Heijde D, Zhou L, Tsuji W, Newmark R; Denosumab Rheumatoid Arthritis Study Group. Denosumab treatment effects on structural damage, bone mineral density, and bone turnover in rheumatoid arthritis: a twelve-month, multicenter, randomized, double-blind, placebo-controlled, phase II clinical trial. Arthritis Rheum. 2008 May;58(5):1299-309. doi: 10.1002/art.23417.
PubMed 18438830
Deodhar A, Dore RK, Mandel D, Schechtman J, Shergy W, Trapp R, Ory PA, Peterfy CG, Fuerst T, Wang H, Zhou L, Tsuji W, Newmark R. Denosumab-mediated increase in hand bone mineral density associated with decreased progression of bone erosion in rheumatoid arthritis patients. Arthritis Care Res (Hoboken). 2010 Apr;62(4):569-74. doi: 10.1002/acr.20004.
PubMed 20391513
Dore RK, Cohen SB, Lane NE, Palmer W, Shergy W, Zhou L, Wang H, Tsuji W, Newmark R; Denosumab RA Study Group. Effects of denosumab on bone mineral density and bone turnover in patients with rheumatoid arthritis receiving concurrent glucocorticoids or bisphosphonates. Ann Rheum Dis. 2010 May;69(5):872-5. doi: 10.1136/ard.2009.112920. Epub 2009 Sep 3.
PubMed 19734132
Sharp JT, Tsuji W, Ory P, Harper-Barek C, Wang H, Newmark R. Denosumab prevents metacarpal shaft cortical bone loss in patients with erosive rheumatoid arthritis. Arthritis Care Res (Hoboken). 2010 Apr;62(4):537-44. doi: 10.1002/acr.20172.
PubMed 20391509

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

RecruitingPhase 2
Study of PTC844 in Participants With Active Rheumatoid Arthritis
Rheumatoid Arthritis
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An Ascending Dose Study of DKB903 in Participants With Rheumatoid Arthritis (RA) and Participants With Systemic Lupus Erythematosus (SLE)
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All Rheumatoid Arthritis trials

Study at a glance

From the registry record, last updated by the sponsor on 25 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized, Double-blind, Placebo-controlled, Multi-dose Phase 2 Study to Determine the Efficacy, Safety and Tolerability of Denosumab in the Treatment of Rheumatoid Arthritis
ClinicalTrials.gov ID: NCT00095498
Acronym / sponsor ID: 20040144
Conditions: Rheumatoid Arthritis
Keywords: arthritis, joint pain, Methotrexate
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 227 participants (actual)
Lead sponsor: AmgenIndustry (pharma, biotech, devices)
Study start: 11 Aug 2004 (actual)
Primary completion: 1 Apr 2007 (actual)
Study completion: 1 Apr 2007 (actual)
First posted: 8 Nov 2004 (estimated)
Results: Posted 13 Jan 2014

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 3

Arm	Type	Receives
Denosumab 180 mg	Experimental	Drug: denosumabParticipants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.
Denosumab 60 mg	Experimental	Drug: denosumabParticipants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.
Placebo	Placebo comparator	Drug: placeboParticipants received placebo subcutaneous injections on Day 1 and at Month 6.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

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

Key exclusion criteria (3 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
placeboplacebo subcutaneous injection	Drug	Placebo
denosumabAlso: AMG 162For subcutaneous injection	Drug	Denosumab 180 mg, Denosumab 60 mg

Primary outcome

Change From Baseline in Rheumatoid Arthritis Erosion Score Measured From MRI Assessments (RA-MRI ES) at Month 6
Time frame: Baseline, 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).

139 secondary outcomes

Change From Baseline in Radiographic Total Modified Sharp Score (TSS) at Month 12
Time frame: Baseline, Month 12
Change From Baseline in Radiographic Total Modified Sharp Score (TSS) at Month 6
Time frame: Baseline, Month 6
Change From Baseline in Radiographic Erosion Score at Month 12
Time frame: Baseline, Month 12
Change From Baseline in Radiographic Erosion Score at Month 6
Time frame: Baseline, Month 6
Change From Baseline in Radiographic Joint Space Narrowing Score at Month 12
Time frame: Baseline, Month 12
Change From Baseline in Radiographic Joint Space Narrowing Score at Month 6
Time frame: Baseline, Month 6
Percent Change From Baseline in Lumbar Spine Bone Mineral Density at Month 1
Time frame: Baseline, Month 1
Percent Change From Baseline in Lumbar Spine Bone Mineral Density at Month 6
Time frame: Baseline, month 6
Percent Change From Baseline in Lumbar Spine Bone Mineral Density at Month 12
Time frame: Baseline, Month 12
Percent Change From Baseline in Femoral Neck Bone Mineral Density at Month 1
Time frame: Baseline, Month 1
Percent Change From Baseline in Femoral Neck Bone Mineral Density at Month 6
Time frame: Baseline, Month 6
Percent Change From Baseline in Femoral Neck Bone Mineral Density at Month 12
Time frame: Baseline, Month 12
Percent Change From Baseline in Total Hip Bone Mineral Density at Month 1
Time frame: Baseline, Month 1
Percent Change From Baseline in Total Hip Bone Mineral Density at Month 6
Time frame: Baseline, Month 6
Percent Change From Baseline in Total Hip Bone Mineral Density at Month 12
Time frame: Baseline, Month 12
Percent Change From Baseline in Serum Collagen C-Telopeptide (CTX) at Month 3
Time frame: Baseline, Month 3
Percent Change From Baseline in Serum CTX at Month 6
Time frame: Baseline, Month 6
Percent Change From Baseline in Serum CTX at Month 12
Time frame: Baseline, Month 12
Percent Change From Baseline in Procollagen 1 N-terminal Peptide (P1NP) at Month 3
Time frame: Baseline, Month 3
Percent Change From Baseline in P1NP at Month 6
Time frame: Baseline, Month 6
Percent Change From Baseline in P1NP at Month 12
Time frame: Baseline, Month 12
Percent Change From Baseline in Urine Type II Collagen C-telopeptide (C-Tx) /Creatinine at Month 3
Time frame: Baseline, Month 3
Percent Change From Baseline in Urine Type II C-Tx /Creatinine at Month 6
Time frame: Baseline, Month 6
Percent Change From Baseline in Urine Type II C-Tx /Creatinine at Month 12
Time frame: Baseline, Month 12
Number of Participants With Anti-Denosumab Binding Antibodies
Time frame: Assessed at Baseline and at Months 1, 3, 6 and 12.
Number of Participants With Anti-Denosumab Binding Antibody and Neutralizing Antibody
Time frame: Baseline to Month 12
Change From Baseline in Albumin at Month 1
Time frame: Baseline, month 1
Change From Baseline in Albumin at Month 3
Time frame: Baseline, month 3
Change From Baseline in Albumin at Month 6
Time frame: Baseline, month 6
Change From Baseline in Albumin at Month 12
Time frame: Baseline, month 12
Change From Baseline in Alkaline Phosphatase at Month 1
Time frame: Baseline, month 1
Change From Baseline in Alkaline Phosphatase at Month 3
Time frame: baseline, month 3
Change From Baseline in Alkaline Phosphatase at Month 6
Time frame: baseline, month 6
Change From Baseline in Alkaline Phosphatase at Month 12
Time frame: baseine, month 12
Change From Baseline in Bicarbonate at Month 1
Time frame: baseline, month 1
Change From Baseline in Bicarbonate at Month 3
Time frame: baseline, month 3
Change From Baseline in Bicarbonate at Month 6
Time frame: Baseline, month 6
Change From Baseline in Bicarbonate at Month 12
Time frame: Baseline, Month 12
Change From Baseline in Total Bilirubin at Month 1
Time frame: baseline, month 1
Change From Baseline in Total Bilirubin at Month 3
Time frame: Baseline, month 3

Results and safety

Results posted to the registry on 13 Jan 2014, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Denosumab 180 mg	76	39
Denosumab 60 mg	73	38
Placebo	78	39

Primary outcome: Change From Baseline in Rheumatoid Arthritis Erosion Score Measured From MRI Assessments (RA-MRI ES) at Month 6

Time frame: Baseline, Month 6. Median (Full Range). Unit: units on a scale

Measure	Denosumab 180 mg n = 65	Denosumab 60 mg n = 67	Placebo n = 66
Value	0.00 (3.49)	0.00 (3.43)	0.49 (5.08)

Denosumab 60 mg vs Placebo: p = 0.264, van Elteren stratified rank test
Denosumab 180 mg vs Placebo: p = 0.018, van Elteren stratified rank test

Population analysed: All randomized patients who received at least 1 dose of investigational product with a non-missing baseline and at least 1 non-missing postbaseline measurement, and with available data at 6 months.

139 secondary outcomes are reported in the full results.

Adverse events

Time frame: 12 months. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo	5 of 75 (6.7%)	47 of 75 (62.7%)	Not reported
Denosumab 60 mg	3 of 71 (4.2%)	44 of 71 (62%)	Not reported
Denosumab 180 mg	6 of 72 (8.3%)	44 of 72 (61.1%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 25 Oct 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 18438830Cohen SB, Dore RK, Lane NE, Ory PA, Peterfy CG, Sharp JT, van der Heijde D, Zhou L, Tsuji W, Newmark R; Denosumab Rheumatoid Arthritis Study Group. Denosumab treatment effects on structural damage, bone mineral density, and bone turnover in rheumatoid arthritis: a twelve-month, multicenter, randomized, double-blind, placebo-controlled, phase II clinical trial. Arthritis Rheum. 2008 May;58(5):1299-309. doi: 10.1002/art.23417.
Background: PubMed 20391513Deodhar A, Dore RK, Mandel D, Schechtman J, Shergy W, Trapp R, Ory PA, Peterfy CG, Fuerst T, Wang H, Zhou L, Tsuji W, Newmark R. Denosumab-mediated increase in hand bone mineral density associated with decreased progression of bone erosion in rheumatoid arthritis patients. Arthritis Care Res (Hoboken). 2010 Apr;62(4):569-74. doi: 10.1002/acr.20004.
Background: PubMed 19734132Dore RK, Cohen SB, Lane NE, Palmer W, Shergy W, Zhou L, Wang H, Tsuji W, Newmark R; Denosumab RA Study Group. Effects of denosumab on bone mineral density and bone turnover in patients with rheumatoid arthritis receiving concurrent glucocorticoids or bisphosphonates. Ann Rheum Dis. 2010 May;69(5):872-5. doi: 10.1136/ard.2009.112920. Epub 2009 Sep 3.
Background: PubMed 20391509Sharp JT, Tsuji W, Ory P, Harper-Barek C, Wang H, Newmark R. Denosumab prevents metacarpal shaft cortical bone loss in patients with erosive rheumatoid arthritis. Arthritis Care Res (Hoboken). 2010 Apr;62(4):537-44. doi: 10.1002/acr.20172.
AmgenTrials clinical trials websiteLink provided by the sponsor.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

MD study director

Amgen

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing denosumab in people with Rheumatoid Arthritis, run by Amgen.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 13 Jan 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in Rheumatoid Arthritis Erosion Score Measured From MRI Assessments (RA-MRI ES) at Month 6 (time frame: Baseline, Month 6). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00095498, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Oct 2021.