NCT01101061

A Single-dose Study Evaluating Romosozumab (AMG 785) in Healthy Postmenopausal Japanese and Non-Japanese Women

Completed Phase 1 Results posted Last updated 31 July 2019

What this trial tests

Phase 1 trial testing Romosozumab in Osteopenia in 31 participants. Completed in 1 November 2010.

Timeline

3 May 2010

Primary endpoint
1 November 2010

1 November 2010

Quick facts

Lead sponsor	Amgen
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	sequential
Masking	double
Primary purpose	treatment
Enrollment	31
Start date	3 May 2010
Primary completion	1 November 2010
Estimated completion	1 November 2010

Drugs / interventions tested

• Romosozumab (romosozumab) — full drug profile →
• Placebo

Conditions studied

• Osteopenia — all drugs for Osteopenia →

Sponsor

Amgen — full company profile →

Who can join

Adults 45 to 70, female only, with Osteopenia. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With Adverse Events Primary · Participants who received a 1 or 3 mg/kg dose (romosozumab or placebo) were followed for 2 months (day 57) after study drug administration and participants who received 5 mg/kg were followed for 3 months (day 85) for safety assessments.

A serious adverse event (SAE) is defined as an adverse event that * is fatal * is life threatening * requires in-patient hospitalization or prolongation of existing hospitalization * results in persistent or significant disability/incapacity * is a congenital anomaly/birth defect * other significant medical hazard. A treatment-related AE is any treatment-emergent AE that per investigator review has a reasonable possibility of being caused by the investigational product.

Any adverse event

Group	Value	95% CI
Japanese Women: Placebo	6
Japanese Women: Romosozumab 1 mg/kg	4
Japanese Women: Romosozumab 3 mg/kg	3
Japanese Women: Romosozumab 5 mg/kg	6
Non-Japanese Women: Placebo	2
Non-Japanese Women: Romosozumab 3 mg/kg	4

Serious adverse events

Group	Value	95% CI
Japanese Women: Placebo	0
Japanese Women: Romosozumab 1 mg/kg	0
Japanese Women: Romosozumab 3 mg/kg	0
Japanese Women: Romosozumab 5 mg/kg	0
Non-Japanese Women: Placebo	0
Non-Japanese Women: Romosozumab 3 mg/kg	0

Treatment-related adverse events

Group	Value	95% CI
Japanese Women: Placebo	2
Japanese Women: Romosozumab 1 mg/kg	1
Japanese Women: Romosozumab 3 mg/kg	2
Japanese Women: Romosozumab 5 mg/kg	1
Non-Japanese Women: Placebo	0
Non-Japanese Women: Romosozumab 3 mg/kg	0

AEs leading to discontinuation of study drug

Group	Value	95% CI
Japanese Women: Placebo	0
Japanese Women: Romosozumab 1 mg/kg	0
Japanese Women: Romosozumab 3 mg/kg	0
Japanese Women: Romosozumab 5 mg/kg	0
Non-Japanese Women: Placebo	0
Non-Japanese Women: Romosozumab 3 mg/kg	0

Deaths

Group	Value	95% CI
Japanese Women: Placebo	0
Japanese Women: Romosozumab 1 mg/kg	0
Japanese Women: Romosozumab 3 mg/kg	0
Japanese Women: Romosozumab 5 mg/kg	0
Non-Japanese Women: Placebo	0
Non-Japanese Women: Romosozumab 3 mg/kg	0

Number of Participants Who Developed Anti-romosozumab Binding Antibodies Primary · Day 29, and end of study (day 57 for participants assigned to 1 or 3 mg/kg romosozumab/placebo or day 85 for participants assigned to 5 mg/kg romosozumab/placebo)

Participants who were negative for anti-romosozumab binding antibodies at baseline with a positive result at any time post-baseline.

Group	Value	95% CI
Japanese Women: Placebo	0
Japanese Women: Romosozumab 1 mg/kg	0
Japanese Women: Romosozumab 3 mg/kg	0
Japanese Women: Romosozumab 5 mg/kg	0
Non-Japanese Women: Placebo	0
Non-Japanese Women: Romosozumab 3 mg/kg	0

Serum Calcium Levels Primary · Baseline, days 2, 3, 4, 6, 8, 12, 22, 29, 43, 57, 71, and 85

Baseline

Group	Value	95% CI
Japanese Women: Placebo	2.34	± 0.04
Japanese Women: Romosozumab 1 mg/kg	2.31	± 0.04
Japanese Women: Romosozumab 3 mg/kg	2.33	± 0.03
Japanese Women: Romosozumab 5 mg/kg	2.38	± 0.03
Non-Japanese Women: Placebo	2.28	± 0.08
Non-Japanese Women: Romosozumab 3 mg/kg	2.45	± 0.04

Day 2

Group	Value	95% CI
Japanese Women: Placebo	2.33	± 0.04
Japanese Women: Romosozumab 1 mg/kg	2.34	± 0.03
Japanese Women: Romosozumab 3 mg/kg	2.31	± 0.03
Japanese Women: Romosozumab 5 mg/kg	2.36	± 0.03
Non-Japanese Women: Placebo	2.34	± 0.04
Non-Japanese Women: Romosozumab 3 mg/kg	2.40	± 0.05

Day 3

Group	Value	95% CI
Japanese Women: Placebo	2.33	± 0.05
Japanese Women: Romosozumab 1 mg/kg	2.36	± 0.04
Japanese Women: Romosozumab 3 mg/kg	2.31	± 0.03
Japanese Women: Romosozumab 5 mg/kg	2.38	± 0.03
Non-Japanese Women: Placebo	2.34	± 0.01
Non-Japanese Women: Romosozumab 3 mg/kg	2.43	± 0.03

Day 4

Group	Value	95% CI
Japanese Women: Placebo	2.32	± 0.05
Japanese Women: Romosozumab 1 mg/kg	2.31	± 0.03
Japanese Women: Romosozumab 3 mg/kg	2.30	± 0.03
Japanese Women: Romosozumab 5 mg/kg	2.32	± 0.03
Non-Japanese Women: Placebo	2.38	± 0.02
Non-Japanese Women: Romosozumab 3 mg/kg	2.36	± 0.04

Day 6

Group	Value	95% CI
Japanese Women: Placebo	2.39	± 0.05
Japanese Women: Romosozumab 1 mg/kg	2.30	± 0.03
Japanese Women: Romosozumab 3 mg/kg	2.31	± 0.04
Japanese Women: Romosozumab 5 mg/kg	2.35	± 0.04
Non-Japanese Women: Placebo	2.28	± 0.02
Non-Japanese Women: Romosozumab 3 mg/kg	2.40	± 0.03

Day 8

Group	Value	95% CI
Japanese Women: Placebo	2.39	± 0.05
Japanese Women: Romosozumab 1 mg/kg	2.25	± 0.02
Japanese Women: Romosozumab 3 mg/kg	2.31	± 0.03
Japanese Women: Romosozumab 5 mg/kg	2.29	± 0.03
Non-Japanese Women: Placebo	2.35	± 0.00
Non-Japanese Women: Romosozumab 3 mg/kg	2.38	± 0.03

Day 12

Group	Value	95% CI
Japanese Women: Placebo	2.35	± 0.06
Japanese Women: Romosozumab 1 mg/kg	2.27	± 0.05
Japanese Women: Romosozumab 3 mg/kg	2.33	± 0.03
Japanese Women: Romosozumab 5 mg/kg	2.28	± 0.02
Non-Japanese Women: Placebo	2.33	± 0.03
Non-Japanese Women: Romosozumab 3 mg/kg	2.28	± 0.04

Day 22

Group	Value	95% CI
Japanese Women: Placebo	2.31	± 0.03
Japanese Women: Romosozumab 1 mg/kg	2.31	± 0.03
Japanese Women: Romosozumab 3 mg/kg	2.28	± 0.05
Japanese Women: Romosozumab 5 mg/kg	2.25	± 0.03
Non-Japanese Women: Placebo	2.33	± 0.00
Non-Japanese Women: Romosozumab 3 mg/kg	2.36	± 0.03

Serum Intact Parathyroid Hormone (iPTH) Levels Primary · Baseline and days 2, 3, 4, 6, 8, 12, 22, 29, 43, 57, 71, and 85

Baseline

Group	Value	95% CI
Japanese Women: Placebo	4.47	± 0.97
Japanese Women: Romosozumab 1 mg/kg	4.24	± 0.70
Japanese Women: Romosozumab 3 mg/kg	4.93	± 0.84
Japanese Women: Romosozumab 5 mg/kg	3.63	± 0.62
Non-Japanese Women: Placebo	3.77	± 1.65
Non-Japanese Women: Romosozumab 3 mg/kg	2.73	± 0.37

Day 2

Group	Value	95% CI
Japanese Women: Placebo	4.51	± 0.78
Japanese Women: Romosozumab 1 mg/kg	4.92	± 0.78
Japanese Women: Romosozumab 3 mg/kg	5.01	± 0.47
Japanese Women: Romosozumab 5 mg/kg	4.23	± 0.54
Non-Japanese Women: Placebo	3.50	± 1.49
Non-Japanese Women: Romosozumab 3 mg/kg	2.57	± 0.23

Day 3

Group	Value	95% CI
Japanese Women: Placebo	4.93	± 0.71
Japanese Women: Romosozumab 1 mg/kg	4.69	± 0.69
Japanese Women: Romosozumab 3 mg/kg	5.38	± 0.44
Japanese Women: Romosozumab 5 mg/kg	4.58	± 0.76
Non-Japanese Women: Placebo	3.50	± 1.06
Non-Japanese Women: Romosozumab 3 mg/kg	2.89	± 0.37

Day 4

Group	Value	95% CI
Japanese Women: Placebo	4.47	± 0.84
Japanese Women: Romosozumab 1 mg/kg	5.09	± 0.69
Japanese Women: Romosozumab 3 mg/kg	5.09	± 0.23
Japanese Women: Romosozumab 5 mg/kg	5.20	± 1.13
Non-Japanese Women: Placebo	3.93	± 1.70
Non-Japanese Women: Romosozumab 3 mg/kg	3.55	± 0.73

Day 6

Group	Value	95% CI
Japanese Women: Placebo	4.21	± 0.67
Japanese Women: Romosozumab 1 mg/kg	4.97	± 0.93
Japanese Women: Romosozumab 3 mg/kg	5.75	± 0.72
Japanese Women: Romosozumab 5 mg/kg	4.44	± 0.77
Non-Japanese Women: Placebo	3.82	± 1.49
Non-Japanese Women: Romosozumab 3 mg/kg	3.66	± 0.66

Day 8

Group	Value	95% CI
Japanese Women: Placebo	4.19	± 0.95
Japanese Women: Romosozumab 1 mg/kg	5.91	± 0.86
Japanese Women: Romosozumab 3 mg/kg	5.23	± 0.68
Japanese Women: Romosozumab 5 mg/kg	4.79	± 0.90
Non-Japanese Women: Placebo	4.14	± 1.91
Non-Japanese Women: Romosozumab 3 mg/kg	3.98	± 0.68

Day 12

Group	Value	95% CI
Japanese Women: Placebo	5.04	± 0.95
Japanese Women: Romosozumab 1 mg/kg	6.42	± 0.59
Japanese Women: Romosozumab 3 mg/kg	5.46	± 0.41
Japanese Women: Romosozumab 5 mg/kg	5.80	± 0.61
Non-Japanese Women: Placebo	4.19	± 1.86
Non-Japanese Women: Romosozumab 3 mg/kg	4.46	± 0.64

Day 22

Group	Value	95% CI
Japanese Women: Placebo	4.69	± 0.74
Japanese Women: Romosozumab 1 mg/kg	5.57	± 0.64
Japanese Women: Romosozumab 3 mg/kg	6.15	± 0.56
Japanese Women: Romosozumab 5 mg/kg	7.09	± 0.84
Non-Japanese Women: Placebo	5.46	± 2.71
Non-Japanese Women: Romosozumab 3 mg/kg	4.62	± 0.68

Maximum Percent Change From Baseline in Serum Procollagen Type 1 N-terminal Propeptide (P1NP) Secondary · Baseline and days 2, 3, 4, 6, 8, 12, 22, 29, 43, 57, 71, and 85

Group	Value	95% CI
Japanese Women: Placebo	26.85	± 6.39
Japanese Women: Romosozumab 1 mg/kg	59.23	± 12.21
Japanese Women: Romosozumab 3 mg/kg	102.57	± 18.26
Japanese Women: Romosozumab 5 mg/kg	196.37	± 29.79
Non-Japanese Women: Placebo	8.30	± 1.78
Non-Japanese Women: Romosozumab 3 mg/kg	164.44	± 35.58

Maximum Percent Change From Baseline in Serum C-telopeptide (CTX) Secondary · Baseline and days 2, 3, 4, 6, 8, 12, 22, 29, 43, 57, 71, and 85

Group	Value	95% CI
Japanese Women: Placebo	-12.64	± 1.40
Japanese Women: Romosozumab 1 mg/kg	-16.19	± 7.36
Japanese Women: Romosozumab 3 mg/kg	-35.92	± 1.94
Japanese Women: Romosozumab 5 mg/kg	-39.17	± 5.13
Non-Japanese Women: Placebo	-25.46	± 8.52
Non-Japanese Women: Romosozumab 3 mg/kg	-43.32	± 9.96

Percent Change From Baseline in Sclerostin Secondary · Baseline and days 12, 29, 43, 57, 71, and 85

Day 12

Group	Value	95% CI
Japanese Women: Placebo	-3.78	± 3.72
Japanese Women: Romosozumab 1 mg/kg	6639.01	± 534.50
Japanese Women: Romosozumab 3 mg/kg	13749.61	± 1091.63
Japanese Women: Romosozumab 5 mg/kg	17028.81	± 1875.81
Non-Japanese Women: Placebo	-17.95	± 6.38
Non-Japanese Women: Romosozumab 3 mg/kg	14652.96	± 1349.38

Day 29

Group	Value	95% CI
Japanese Women: Placebo	591.80	± 596.47
Japanese Women: Romosozumab 1 mg/kg	1602.70	± 231.77
Japanese Women: Romosozumab 3 mg/kg	7667.80	± 675.45
Japanese Women: Romosozumab 5 mg/kg	12723.54	± 2138.65
Non-Japanese Women: Placebo	-14.54	± 1.78
Non-Japanese Women: Romosozumab 3 mg/kg	9581.13	± 1283.73

Day 43

Group	Value	95% CI
Japanese Women: Placebo	-15.43	± 11.39
Japanese Women: Romosozumab 1 mg/kg	467.07	± 55.62
Japanese Women: Romosozumab 3 mg/kg	3384.02	± 613.99
Japanese Women: Romosozumab 5 mg/kg	6844.74	± 1730.04
Non-Japanese Women: Placebo	-9.35	± 4.59
Non-Japanese Women: Romosozumab 3 mg/kg	4487.33	± 1771.30

Day 57

Group	Value	95% CI
Japanese Women: Placebo	-17.89	± 11.96
Japanese Women: Romosozumab 1 mg/kg	167.37	± 28.33
Japanese Women: Romosozumab 3 mg/kg	911.23	± 156.09
Japanese Women: Romosozumab 5 mg/kg	2836.61	± 1109.97
Non-Japanese Women: Placebo	-0.41	± 12.65
Non-Japanese Women: Romosozumab 3 mg/kg	1826.83	± 917.98

Day 71

Group	Value	95% CI
Japanese Women: Placebo	-39.80	± 3.87
Japanese Women: Romosozumab 5 mg/kg	997.02	± 532.06

Day 85

Group	Value	95% CI
Japanese Women: Placebo	-27.41	± 2.02
Japanese Women: Romosozumab 5 mg/kg	415.38	± 243.40

Time to Maximum Observed Concentration of Romosozumab Secondary · Predose, 12 hours postdose, and on days 2, 3, 4, 6, 8, 12, 22, 29, 43, and 57, and days 71 and 85 for participants assigned tp 5 mg/kg romosozumab/placebo.

Serum concentrations of romosozumab were measured using a validated enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) was 50 ng/mL.

Group	Value	95% CI
Japanese Women: Romosozumab 1 mg/kg	5.0	5.0 – 8.0
Japanese Women: Romosozumab 3 mg/kg	5.0	3.0 – 12
Japanese Women: Romosozumab 5 mg/kg	5.0	5.0 – 7.0
Non-Japanese Women: Romosozumab 3 mg/kg	5.0	5.0 – 7.0

Maximum Observed Concentration of Romosozumab Secondary · Predose, 12 hours postdose, and on days 2, 3, 4, 6, 8, 12, 22, 29, 43, and 57, and days 71 and 85 for participants assigned tp 5 mg/kg romosozumab/placebo.

Serum concentrations of romosozumab were measured using a validated enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) was 50 ng/mL.

Group	Value	95% CI
Japanese Women: Romosozumab 1 mg/kg	4.06	± 1.45
Japanese Women: Romosozumab 3 mg/kg	17.1	± 4.7
Japanese Women: Romosozumab 5 mg/kg	33.8	± 8.1
Non-Japanese Women: Romosozumab 3 mg/kg	18.6	± 1.1

Area Under the Serum Concentration-time Curve From Time 0 to the Last Quantifiable Concentration (AUClast) of Romosozumab Secondary · Predose, 12 hours postdose, and on days 2, 3, 4, 6, 8, 12, 22, 29, 43, and 57, and days 71 and 85 for participants assigned tp 5 mg/kg romosozumab/placebo.

Serum concentrations of romosozumab were measured using a validated enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) was 50 ng/mL.

Group	Value	95% CI
Japanese Women: Romosozumab 1 mg/kg	64.0	± 27.0
Japanese Women: Romosozumab 3 mg/kg	344	± 90
Japanese Women: Romosozumab 5 mg/kg	804	± 320
Non-Japanese Women: Romosozumab 3 mg/kg	412	± 136

Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) for Romosozumab Secondary · Predose, 12 hours postdose, and on days 2, 3, 4, 6, 8, 12, 22, 29, 43, and 57, and days 71 and 85 for participants assigned tp 5 mg/kg romosozumab/placebo.

Serum concentrations of romosozumab were measured using a validated enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) was 50 ng/mL.

Group	Value	95% CI
Japanese Women: Romosozumab 1 mg/kg	64.7	± 26.8
Japanese Women: Romosozumab 3 mg/kg	347	± 90
Japanese Women: Romosozumab 5 mg/kg	806	± 323
Non-Japanese Women: Romosozumab 3 mg/kg	421	± 147

Apparent Clearance (CL/F) of Romosozumab Secondary · Predose, 12 hours postdose, and on days 2, 3, 4, 6, 8, 12, 22, 29, 43, and 57, and days 71 and 85 for participants assigned tp 5 mg/kg romosozumab/placebo.

Serum concentrations of romosozumab were measured using a validated enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) was 50 ng/mL.

Group	Value	95% CI
Japanese Women: Romosozumab 1 mg/kg	18.6	± 10.0
Japanese Women: Romosozumab 3 mg/kg	9.27	± 2.64
Japanese Women: Romosozumab 5 mg/kg	6.98	± 2.35
Non-Japanese Women: Romosozumab 3 mg/kg	7.91	± 2.68

Adverse events — posted to ClinicalTrials.gov

Time frame: Participants who received a 1 or 3 mg/kg dose (romosozumab or placebo) were followed for 2 months (day 57) after study drug administration and participants who received 5 mg/kg were followed for 3 months (day 85) for safety assessments. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Japanese Women: Placebo

Serious: 0/6 (0%)

Deaths: 0/6

Japanese Women: Romosozumab 1 mg/kg

Serious: 0/6 (0%)

Deaths: 0/6

Japanese Women: Romosozumab 3 mg/kg

Serious: 0/6 (0%)

Deaths: 0/6

Japanese Women: Romosozumab 5 mg/kg

Serious: 0/6 (0%)

Deaths: 0/6

Non-Japanese Women: Placebo

Serious: 0/2 (0%)

Deaths: 0/2

Non-Japanese Women: Romosozumab 3 mg/kg

Serious: 0/4 (0%)

Deaths: 0/4

Other adverse events (31 terms — click to expand)

Reaction	System	Japanese Women: Placebo	Japanese Women: Romosozuma…	Japanese Women: Romosozuma…	Japanese Women: Romosozuma…	Non-Japanese Women: Placebo	Non-Japanese Women: Romoso…
Headache	Nervous system disorders	—	—	—	—	—	—
Injection site haematoma	General disorders	—	—	—	—	—	—
Vessel puncture site haematoma	General disorders	—	—	—	—	—	—
Abdominal pain upper	Gastrointestinal disorders	—	—	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—	—	—
Mouth ulceration	Gastrointestinal disorders	—	—	—	—	—	—
Stomatitis	Gastrointestinal disorders	—	—	—	—	—	—
Fatigue	General disorders	—	—	—	—	—	—
Injection site haemorrhage	General disorders	—	—	—	—	—	—
Injection site pruritus	General disorders	—	—	—	—	—	—
Vessel puncture site haemorrhage	General disorders	—	—	—	—	—	—
Gastroenteritis	Infections and infestations	—	—	—	—	—	—
Herpes virus infection	Infections and infestations	—	—	—	—	—	—
Upper respiratory tract infection	Infections and infestations	—	—	—	—	—	—
Viral infection	Infections and infestations	—	—	—	—	—	—
Arthropod bite	Injury, poisoning and procedural complications	—	—	—	—	—	—
Muscle strain	Injury, poisoning and procedural complications	—	—	—	—	—	—
Post procedural swelling	Injury, poisoning and procedural complications	—	—	—	—	—	—
Venomous sting	Injury, poisoning and procedural complications	—	—	—	—	—	—
Transaminases increased	Investigations	—	—	—	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—
Muscle twitching	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—
Myalgia	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—
Somnolence	Nervous system disorders	—	—	—	—	—	—
Vaginal haemorrhage	Reproductive system and breast disorders	—	—	—	—	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—
Throat irritation	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—
Alopecia	Skin and subcutaneous tissue disorders	—	—	—	—	—	—
Pruritus	Skin and subcutaneous tissue disorders	—	—	—	—	—	—
Eye irritation	Eye disorders	—	—	—	—	—	—

Data from ClinicalTrials.gov NCT01101061 adverse events section.

Sponsor's own description

The main purpose of this study is to assess the safety, tolerability and potential immune response to romosozumab following single subcutaneous (SC; injection under the skin) dose administration in healthy postmenopausal Japanese and non-Japanese women.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

1. Romosozumab for the treatment of osteoporosis.
   McClung MR. · · 2018 · cited 49× · PMID 30775535 · DOI 10.1016/j.afos.2018.03.002
2. Sclerostin Antibody Therapy for the Treatment of Osteoporosis: Clinical Prospects and Challenges.
   MacNabb C, Patton D, Hayes JS. · · 2016 · cited 44× · PMID 27313945 · DOI 10.1155/2016/6217286
3. Sclerostin inhibition: a novel therapeutic approach in the treatment of osteoporosis.
   Shah AD, Shoback D, Lewiecki EM. · · 2015 · cited 40× · PMID 26082665 · DOI 10.2147/ijwh.s73244