OsteoporosisPhase 1NCT01833754
Study of Romosozumab (AMG 785) Administered to Healthy Participants and Patients With Stage 4 Renal Impairment or Stage 5 Renal Impairment Requiring Hemodialysis
A Phase 1 study testing Romosozumab in people with Osteoporosis, run by Amgen at 5 sites in United States.
Trial summary
The purpose of this study is to evaluate the safety, tolerability, and immunogenicity profile of romosozumab after a single 210 mg subcutaneous dose in healthy participants and patients with stage 4 renal impairment (RI) or stage 5 RI requiring hemodialysis. Read more about this study
- Who is it for?
- Ages 50 years and olderHealthy volunteers can take part
- Conditions the study is for
- Osteoporosis
- What is being tested?
- Romosozumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 5 sitesUnited States
- Study dates
- 22 Apr 2013to 19 Feb 2014
- Phase
- Phase 1
- 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 50 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Males or females ≥ 50 years of age
- Body weight ≥ 45 and ≤ 110 kg
- Willing to adhere to calcium and vitamin D supplementation requirements
- Females must be of non-reproductive potential
- INCLUSION CRITERIA - SUBJECTS WITH RENAL IMPAIRMENT (GROUPS 1 AND 2):
- Group 1 - Stage 4 RI (estimated glomerular filtration rate (eGFR) 15-29 mL/min/1.73 m²)
- Group 2 - End stage renal disease requiring hemodialysis
- Renal function defined as an estimated glomerular filtration rate (eGFR) ≥ 80 mL/min/1.73 m²
Who cannot join
- History of metabolic or bone disease (except for metabolic bone disease in renal impairment (RI) subjects)
- History of osteoporosis, vertebral fracture, or fragility fracture of the wrist, humerus, hip, or pelvis after age 50
- Recent bone fracture
- Vitamin D insufficiency
- Hypocalcemia or hypercalcemia
- Hypomagnesemia
Show all 18Show fewer
- Hypophosphatemia
- Untreated hyper- or hypothyroidism
- Females with a positive pregnancy test
- Males with pregnant partners
- Females who are lactating/breastfeeding or plan to breastfeed on study and for 3 months after receiving the dose of study drug
- History of spinal stenosis
- History of facial nerve paralysis
- Positive for human immunodeficiency virus (HIV) antibodies
- Positive for hepatitis B surface antigen or detectable hepatitis C
- Malignancy (except fully resected cutaneous basal cell or squamous cell carcinoma, cervical, or breast ductal carcinoma in situ) within 5 years before screening
- History of solid organ or bone marrow transplants EXCLUSION CRITERIA - HEALTHY SUBJECTS (GROUP 3)
- Current hyper- or hypoparathyroidism
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Research Site
Denver, Colorado, 80230
Research Site
Los Angeles, California, 90022
Research Site
Orangeburg, South Carolina, 29118
Research Site
Pembroke Pines, Florida, 33028
Research Site
Tempe, Arizona, 85284
About this study
Official title: A Phase 1, Open-label, Single-dose Study of Romosozumab (AMG 785) Administered Subcutaneously to Healthy Subjects and Subjects With Stage 4 Renal Impairment or Stage 5 Renal Impairment Requiring Hemodialysis
The purpose of this study is to evaluate the safety, tolerability, and immunogenicity profile of romosozumab after a single 210 mg subcutaneous dose in healthy participants and patients with stage 4 renal impairment (RI) or stage 5 RI requiring hemodialysis.
- Conditions
- Osteoporosis
- Being tested
- Romosozumab
- Keywords
- Osteoporosis, Bone, Renal, Insufficiency, Kidney, Hemodialysis, Impairment
- Medical subject headings
- Osteoporosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RomosozumabDrug
Also called AMG 785, EVENITY™
Administered as three 70 mg/mL prefilled syringe injections
| Study group | Role | What they receive |
|---|---|---|
| Group 1: Stage 4 Renal Impairment | Experimental | Participants with stage 4 renal impairment (defined as an estimated glomerular filtration rate [eGFR] 15 to 29 mL/min/1.73 m²) received a single subcutaneous injection of 210 mg romosozumab on day 1. Receives: Drug: Romosozumab |
| Group 2: ESRD Requiring Hemodialysis | Experimental | Participants with end stage renal disease (ESRD) requiring hemodialysis received a single subcutaneous injection of 210 mg romosozumab on day 1. Receives: Drug: Romosozumab |
| Group 3: Healthy Participants | Experimental | Healthy participants (eGFR ≥ 80 mL/min/1.73 m²) received a single subcutaneous injection of 210 mg romosozumab on day 1. Receives: Drug: Romosozumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Adverse Events
A serious adverse event was defined as an adverse event (AE) that met at least 1 of the following serious criteria:
- fatal
- life-threatening
- required in-patient hospitalization or prolongation of existing hospitalization
- resulted in persistent or significant disability/incapacity
- congenital anomaly/birth defect
- other medically important serious event. A treatment-related adverse event (TRAE) was an AE assessed by the investigator as possibly related to the study drug, indicated by a "yes" response to the question: "Is there a reasonable possibility that the event may have been caused by the investigational product?"
Measured: From the first dose of study drug up to day 85
Number of Participants Who Developed Anti-Romosozumab Antibodies
Two validated assays were used to detect the presence of anti-romosozumab antibodies. First, an electrochemiluminescent immunoassay was used to detect binding antibodies (screening assay) and confirm antibodies (confirmatory assay) capable of binding romosozumab. Second, a non-cell-based competitive binding bioassay was used to test positive binding antibody samples for neutralizing activity against romosozumab.
If a sample was positive for binding antibodies and demonstrated neutralizing activity at the same time point, the participant was defined as positive for neutralizing antibodies.
Measured: Baseline and day 85
Albumin-Adjusted Serum Calcium Concentrations by Visit
Albumin-adjusted calcium was derived as:
Where serum albumin < 40 g/L then albumin-adjusted calcium = measured total calcium (mmol/L) + 0.02 * [40 - serum albumin (g/L)]; Where serum albumin ≥ 40 g/L then albumin-adjusted calcium = measured total calcium.
Measured: Baseline, days 8, 15, 22, 29, 43, 57, and 85/end of study visit
Intact Parathyroid Hormone (iPTH)Concentrations by Visit
Measured: Baseline, days 8, 15, 22, 29, 43, 57, and 85/end of study visit
Secondary outcomes (4)
Maximum Observed Serum Concentration (Cmax) of Romosozumab
Measured: Pre-dose on day -1 and on days 2, 3, 4, 6, 8, 11, 15, 18, 22, 29, 36, 43, 57 and 85
Time to Maximum Observed Serum Concentration (Tmax) of Romosozumab
Measured: Pre-dose on day -1 and on days 2, 3, 4, 6, 8, 11, 15, 18, 22, 29, 36, 43, 57 and 85
Area Under the Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast)
Measured: Pre-dose on day -1 and on days 2, 3, 4, 6, 8, 11, 15, 18, 22, 29, 36, 43, 57 and 85
Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf)
Measured: Pre-dose on day -1 and on days 2, 3, 4, 6, 8, 11, 15, 18, 22, 29, 36, 43, 57 and 85
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Apr 2013 (estimated)
- Study start22 Apr 2013
- Primary completion19 Feb 2014
- Study completion19 Feb 2014
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 (1)Papers the sponsor has linked to this study.
- Other trials for OsteoporosisStudies 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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amgen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- MD, Study director, Amgen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01833754
- Sponsor's protocol ID
- 20110227
- Status last verified
- Jul 2022
- First submitted
- 15 Apr 2013
- Last updated
- 22 Jul 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Hsu CP, Maddox J, Block G, Bartley Y, Yu Z. Influence of Renal Function on Pharmacokinetics, Pharmacodynamics, and Safety of a Single Dose of Romosozumab. J Clin Pharmacol. 2022 Sep;62(9):1132-1141. doi: 10.1002/jcph.2050. Epub 2022 Apr 2.
PubMed 35304747
Study at a glance
From the registry record, last updated by the sponsor on 22 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Open-label, Single-dose Study of Romosozumab (AMG 785) Administered Subcutaneously to Healthy Subjects and Subjects With Stage 4 Renal Impairment or Stage 5 Renal Impairment Requiring Hemodialysis
- ClinicalTrials.gov ID
- NCT01833754
- Acronym / sponsor ID
- 20110227
- Conditions
- Osteoporosis
- Keywords
- Osteoporosis, Bone, Renal, Insufficiency, Kidney, Hemodialysis, Impairment
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- AmgenIndustry (pharma, biotech, devices)
- Study start
- 22 Apr 2013 (actual)
- Primary completion
- 19 Feb 2014 (actual)
- Study completion
- 19 Feb 2014 (actual)
- First posted
- 17 Apr 2013 (estimated)
- Results
- Posted 25 Feb 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the safety, tolerability, and immunogenicity profile of romosozumab after a single 210 mg subcutaneous dose in healthy participants and patients with stage 4 renal impairment (RI) or stage 5 RI requiring hemodialysis.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Group 1: Stage 4 Renal Impairment | Experimental | Drug: RomosozumabParticipants with stage 4 renal impairment (defined as an estimated glomerular filtration rate [eGFR] 15 to 29 mL/min/1.73 m²) received a single subcutaneous injection of 210 mg romosozumab on day 1. |
| Group 2: ESRD Requiring Hemodialysis | Experimental | Drug: RomosozumabParticipants with end stage renal disease (ESRD) requiring hemodialysis received a single subcutaneous injection of 210 mg romosozumab on day 1. |
| Group 3: Healthy Participants | Experimental | Drug: RomosozumabHealthy participants (eGFR ≥ 80 mL/min/1.73 m²) received a single subcutaneous injection of 210 mg romosozumab on day 1. |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Males or females ≥ 50 years of age
- Body weight ≥ 45 and ≤ 110 kg
- Willing to adhere to calcium and vitamin D supplementation requirements
- Females must be of non-reproductive potential
- Group 1 - Stage 4 RI (estimated glomerular filtration rate (eGFR) 15-29 mL/min/1.73 m²)
Key exclusion criteria (18 listed)
- History of metabolic or bone disease (except for metabolic bone disease in renal impairment (RI) subjects)
- History of osteoporosis, vertebral fracture, or fragility fracture of the wrist, humerus, hip, or pelvis after age 50
- Recent bone fracture
- Vitamin D insufficiency
- Hypocalcemia or hypercalcemia
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 |
|---|---|---|
| RomosozumabAlso: AMG 785, EVENITY™Administered as three 70 mg/mL prefilled syringe injections | Drug | Group 1: Stage 4 Renal Impairment, Group 2: ESRD Requiring Hemodialysis, Group 3: Healthy Participants |
Primary outcome
Number of Participants With Adverse Events
Time frame: From the first dose of study drug up to day 85
A serious adverse event was defined as an adverse event (AE) that met at least 1 of the following serious criteria: * fatal * life-threatening * required in-patient hospitalization or prolongation of existing hospitalization * resulted in persistent or significant disability/incapacity * congenital anomaly/birth defect * other medically important serious event. A treatment-related adverse event (TRAE) was an AE assessed by the investigator as possibly related to the study drug, indicated by a "yes" response to the question: "Is there a reasonable possibility that the event may have been caused by the investigational product?"
Number of Participants Who Developed Anti-Romosozumab Antibodies
Time frame: Baseline and day 85
Two validated assays were used to detect the presence of anti-romosozumab antibodies. First, an electrochemiluminescent immunoassay was used to detect binding antibodies (screening assay) and confirm antibodies (confirmatory assay) capable of binding romosozumab. Second, a non-cell-based competitive binding bioassay was used to test positive binding antibody samples for neutralizing activity against romosozumab. If a sample was positive for binding antibodies and demonstrated neutralizing activity at the same time point, the participant was defined as positive for neutralizing antibodies.
Albumin-Adjusted Serum Calcium Concentrations by Visit
Time frame: Baseline, days 8, 15, 22, 29, 43, 57, and 85/end of study visit
Albumin-adjusted calcium was derived as: Where serum albumin < 40 g/L then albumin-adjusted calcium = measured total calcium (mmol/L) + 0.02 * [40 - serum albumin (g/L)]; Where serum albumin ≥ 40 g/L then albumin-adjusted calcium = measured total calcium.
Intact Parathyroid Hormone (iPTH)Concentrations by Visit
Time frame: Baseline, days 8, 15, 22, 29, 43, 57, and 85/end of study visit
4 secondary outcomes
Maximum Observed Serum Concentration (Cmax) of Romosozumab
Time frame: Pre-dose on day -1 and on days 2, 3, 4, 6, 8, 11, 15, 18, 22, 29, 36, 43, 57 and 85
Time to Maximum Observed Serum Concentration (Tmax) of Romosozumab
Time frame: Pre-dose on day -1 and on days 2, 3, 4, 6, 8, 11, 15, 18, 22, 29, 36, 43, 57 and 85
Area Under the Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast)
Time frame: Pre-dose on day -1 and on days 2, 3, 4, 6, 8, 11, 15, 18, 22, 29, 36, 43, 57 and 85
Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf)
Time frame: Pre-dose on day -1 and on days 2, 3, 4, 6, 8, 11, 15, 18, 22, 29, 36, 43, 57 and 85
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jul 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 35304747Hsu CP, Maddox J, Block G, Bartley Y, Yu Z. Influence of Renal Function on Pharmacokinetics, Pharmacodynamics, and Safety of a Single Dose of Romosozumab. J Clin Pharmacol. 2022 Sep;62(9):1132-1141. doi: 10.1002/jcph.2050. Epub 2022 Apr 2.
- 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
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Romosozumab in people with Osteoporosis, run by Amgen at 5 sites in United States.
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 8 inclusion and 18 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 22 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 25 Feb 2019). 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?
Number of Participants With Adverse Events (time frame: From the first dose of study drug up to day 85). The study lists 4 primary outcomes in all. 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 NCT01833754, which also lists 1 linked publication.
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 22 Jul 2022.