Trial Outcomes & Findings for A Double-blind Study to Assess the Efficacy and Safety of Denosumab Produced by Two Different Processes in Postmenopausal Women With Osteoporosis (NCT NCT02157948)

Last Updated: 2017-08-16

Results Overview

Lumbar spine bone mineral density (BMD) was measured by dual x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

394 participants

Primary outcome timeframe

Baseline and Month 12

Results posted on

2017-08-16

Participant Flow

This study was conducted at 21 centers in Poland, Denmark, United States (US), and Canada. The first participant enrolled on 05 May 2014 and the last participant enrolled on 03 July 2014.

Ambulatory postmenopausal women 55 years or older with a bone mineral density (BMD) equivalent to a T-score of ≤ 2.5 at lumbar spine, total hip, or femoral neck were eligible to enroll. Five hundred and forty-seven women were screened; 394 were enrolled and 153 did not meet eligibility criteria.

Participant milestones

Participant milestones
Measure	Denosumab CP2 Participants received 60 mg denosumab manufactured using the current CP2 process subcutaneously once every 6 months for 1 year.	Denosumab CP4 Participants received 60 mg denosumab manufactured using the new CP4 process subcutaneously once every 6 months for 1 year.
Overall Study STARTED	197	197
Overall Study Received Treatment	196	196
Overall Study COMPLETED	188	188
Overall Study NOT COMPLETED	9	9

Reasons for withdrawal

Reasons for withdrawal
Measure	Denosumab CP2 Participants received 60 mg denosumab manufactured using the current CP2 process subcutaneously once every 6 months for 1 year.	Denosumab CP4 Participants received 60 mg denosumab manufactured using the new CP4 process subcutaneously once every 6 months for 1 year.
Overall Study Withdrawal by Subject	4	5
Overall Study Lost to Follow-up	3	2
Overall Study Protocol Specified Criteria	2	1
Overall Study Decision by Sponsor	0	1

Baseline Characteristics

A Double-blind Study to Assess the Efficacy and Safety of Denosumab Produced by Two Different Processes in Postmenopausal Women With Osteoporosis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Denosumab CP2 n=197 Participants Participants received 60 mg denosumab manufactured using the current CP2 process subcutaneously once every 6 months for 1 year.	Denosumab CP4 n=197 Participants Participants received 60 mg denosumab manufactured using the new CP4 process subcutaneously once every 6 months for 1 year.	Total n=394 Participants Total of all reporting groups
Age, Continuous	68.0 years STANDARD_DEVIATION 6.8 • n=5 Participants	68.3 years STANDARD_DEVIATION 7.3 • n=7 Participants	68.1 years STANDARD_DEVIATION 7.0 • n=5 Participants
Age, Customized < 65 years	65 participants n=5 Participants	70 participants n=7 Participants	135 participants n=5 Participants
Age, Customized ≥ 65 years	132 participants n=5 Participants	127 participants n=7 Participants	259 participants n=5 Participants
Sex: Female, Male Female	197 Participants n=5 Participants	197 Participants n=7 Participants	394 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized White	190 participants n=5 Participants	195 participants n=7 Participants	385 participants n=5 Participants
Race/Ethnicity, Customized Asian	4 participants n=5 Participants	1 participants n=7 Participants	5 participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	2 participants n=5 Participants	1 participants n=7 Participants	3 participants n=5 Participants
Race/Ethnicity, Customized Other	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Lumbar Spine Bone Mineral Density (BMD) Score	-2.75 T-score STANDARD_DEVIATION 0.91 • n=5 Participants	-2.75 T-score STANDARD_DEVIATION 0.75 • n=7 Participants	-2.75 T-score STANDARD_DEVIATION 0.83 • n=5 Participants
Serum Type I Collagen C-telopeptide (CTX-1)	0.433 ng/mL n=5 Participants	0.462 ng/mL n=7 Participants	0.452 ng/mL n=5 Participants
Serum Procollagen Type 1 N-terminal Propeptide (P1NP)	56.6 μg/L n=5 Participants	61.5 μg/L n=7 Participants	59.3 μg/L n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Month 12

Population: The primary efficacy analysis subset included all randomized participants who had a baseline lumbar spine DXA BMD measurement and at least 1 postbaseline lumbar spine DXA BMD measurement. Postbaseline BMD values obtained at the early termination visit were carried forward as the month-12 value.

Lumbar spine bone mineral density (BMD) was measured by dual x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center.

Outcome measures

Outcome measures
Measure	Denosumab CP2 n=187 Participants Participants received 60 mg denosumab manufactured using the current CP2 process subcutaneously once every 6 months for 1 year.	Denosumab CP4 n=188 Participants Participants received 60 mg denosumab manufactured using the new CP4 process subcutaneously once every 6 months for 1 year.
Percent Change From Baseline in Lumbar Spine BMD	5.78 percent change Standard Deviation 3.44	5.73 percent change Standard Deviation 3.08

SECONDARY outcome

Timeframe: Baseline, month 1, month 6 and month 12

Population: The bone turnover marker (BTM) efficacy analysis subset includes all randomized participants who had a baseline measurement and at least one post baseline measurement. "n" indicates the number of participants with available data at each time point.

Outcome measures

Outcome measures
Measure	Denosumab CP2 n=196 Participants Participants received 60 mg denosumab manufactured using the current CP2 process subcutaneously once every 6 months for 1 year.	Denosumab CP4 n=193 Participants Participants received 60 mg denosumab manufactured using the new CP4 process subcutaneously once every 6 months for 1 year.
Percent Change From Baseline in Serum Type I Collagen C-telopeptide (sCTX) Month 6 (n = 191, 189)	-76.46 percent change Interval -85.58 to -60.58	-79.48 percent change Interval -87.06 to -66.86
Percent Change From Baseline in Serum Type I Collagen C-telopeptide (sCTX) Month 12 (n = 187, 188)	-71.34 percent change Interval -83.33 to -47.13	-75.44 percent change Interval -85.88 to -61.9
Percent Change From Baseline in Serum Type I Collagen C-telopeptide (sCTX) Month 1 (n = 195, 193)	-86.39 percent change Interval -90.65 to -78.45	-88.05 percent change Interval -91.12 to -80.79

SECONDARY outcome

Timeframe: Baseline, month 1, month 6 and month 12

Outcome measures

Outcome measures
Measure	Denosumab CP2 n=196 Participants Participants received 60 mg denosumab manufactured using the current CP2 process subcutaneously once every 6 months for 1 year.	Denosumab CP4 n=193 Participants Participants received 60 mg denosumab manufactured using the new CP4 process subcutaneously once every 6 months for 1 year.
Percent Change From Baseline in Serum Procollagen Type 1 N-terminal Propeptide (P1NP) Month 1 (n = 195, 193)	-29.59 percent change Interval -38.06 to -20.02	-29.86 percent change Interval -38.8 to -20.9
Percent Change From Baseline in Serum Procollagen Type 1 N-terminal Propeptide (P1NP) Month 6 (n = 192, 190)	-76.63 percent change Interval -82.9 to -66.69	-77.74 percent change Interval -85.02 to -70.31
Percent Change From Baseline in Serum Procollagen Type 1 N-terminal Propeptide (P1NP) Month 12 (n = 186, 188)	-71.44 percent change Interval -77.64 to -57.35	-72.08 percent change Interval -80.24 to -62.4

Adverse Events

Denosumab CP2

Serious events: 13 serious events

Other events: 25 other events

Deaths: 0 deaths

Denosumab CP4

Serious events: 6 serious events

Other events: 36 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Denosumab CP2 n=196 participants at risk Participants received 60 mg denosumab manufactured using the current CP2 process subcutaneously once every 6 months for 1 year.	Denosumab CP4 n=196 participants at risk Participants received 60 mg denosumab manufactured using the new CP4 process subcutaneously once every 6 months for 1 year.
Infections and infestations Nasopharyngitis	7.7% 15/196 • 12 months Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	10.7% 21/196 • 12 months Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Arthralgia	5.6% 11/196 • 12 months Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	7.7% 15/196 • 12 months Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.

Additional Information

Study Director

Amgen Inc.

Phone: 866-572-6436

Results disclosure agreements

Principal investigator is a sponsor employee The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
Publication restrictions are in place

Restriction type: OTHER

Measure	Denosumab CP2 n=196 participants at risk Participants received 60 mg denosumab manufactured using the current CP2 process subcutaneously once every 6 months for 1 year.	Denosumab CP4 n=196 participants at risk Participants received 60 mg denosumab manufactured using the new CP4 process subcutaneously once every 6 months for 1 year.
Blood and lymphatic system disorders Anaemia	0.51% 1/196 • 12 months Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/196 • 12 months Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Cardiac disorders Arrhythmia	0.51% 1/196 • 12 months Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/196 • 12 months Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Ear and labyrinth disorders Vertigo	0.51% 1/196 • 12 months Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/196 • 12 months Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Endocrine disorders Goitre	0.51% 1/196 • 12 months Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/196 • 12 months Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Abdominal pain	0.51% 1/196 • 12 months Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/196 • 12 months Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Appendicitis	0.00% 0/196 • 12 months Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.51% 1/196 • 12 months Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Diverticulitis	0.51% 1/196 • 12 months Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.51% 1/196 • 12 months Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Injury, poisoning and procedural complications Femur fracture	0.51% 1/196 • 12 months Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/196 • 12 months Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Injury, poisoning and procedural complications Incision site haematoma	0.00% 0/196 • 12 months Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.51% 1/196 • 12 months Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Injury, poisoning and procedural complications Pulmonary contusion	0.00% 0/196 • 12 months Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.51% 1/196 • 12 months Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Benign ovarian tumour	0.00% 0/196 • 12 months Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.51% 1/196 • 12 months Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.51% 1/196 • 12 months Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/196 • 12 months Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colorectal cancer	0.51% 1/196 • 12 months Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/196 • 12 months Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Carotid artery stenosis	1.0% 2/196 • 12 months Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/196 • 12 months Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Ischaemic stroke	1.0% 2/196 • 12 months Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/196 • 12 months Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Loss of consciousness	0.00% 0/196 • 12 months Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.51% 1/196 • 12 months Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.51% 1/196 • 12 months Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/196 • 12 months Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Surgical and medical procedures Cholecystectomy	0.51% 1/196 • 12 months Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/196 • 12 months Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Vascular disorders Hypertension	0.51% 1/196 • 12 months Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.51% 1/196 • 12 months Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.