OsteoporosisPhase 1NCT03242512
Assessment of Anti-RANKL Antibody in Post-menopausal Women
A Phase 1 study testing TK006 in people with Osteoporosis, run by Jiangsu T-Mab Biopharma Co.,Ltd at 1 site in China.
Trial summary
This is a single-center, open-label, dose-escalating study to evaluate the safety, pharmacokinetics, immunogenicity, and preliminary efficacy of single dose subcutaneous injection of a fully human monoclonal antibody of receptor activator for nuclear factor-κ B ligand (RNAKL) (code name: TK006) in postmenopausal women. Read more about this study
- Who is it for?
- Ages Up to 65 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Osteoporosis
- What is being tested?
- TK006
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteChina
- Study dates
- 7 Aug 2017to 30 Dec 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 Up to 65 years
- Women only
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- Subjects who provide informed consent voluntarily;
- Women who are postmenopausal defined as being amenorrheic for at least 24-month, and follicule-stimulating hormone (FSH)>40 U/L, estradiol (E2)<110pmol/L (or <30pg/mL) as well;
- ≤65 years old, with no restricted activity.
Who cannot join
- Known hypersensitivity to similar medicines or other products derived from mammalian cells, or medical history of severe allergic to foods or medicines;
- Treatment with diphosphonate or fluoride, oestrogen, selective estrogen receptor modulators, calcitonin, parathyroid hormone, high dose Vitamin D (≥1000 IU/day), anabolic steroids, systemic glucocorticoids within 12-month before dosing, or administered with calcitriol within 6 months before dosing;
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) >2.0 times the upper limit of normal (ULN), or alkaline phosphatase (ALP)>1.5×ULN, or Total bilirubin (TBIL) >1.5×ULN, creatinine clearance rate<60 mL/min;
- Disorders that could affect the study outcomes, such as osteomalacia, dysostosis, Paget's disease, Cushing syndrome, hyperprolactinemia, rheumatoid arthritis, hyperparathyroidism, hypoparathyroidism, or other diseases that could affect bone metabolism;
- Hyperthyroidism or hypothyroidism, unless hypothyroidism patients are receiving regular treatment with thyroid hormone and:
- Thyroid stimulating hormone (TSH) is normal, or
Show all 17Show fewer
- TSH>4.78μIU/Ml, ≤10.0μIU/mL and thyroxine (T4) is normal.
- Malabsorption syndrome or other disorders that could affect intestinal absorption function, such as Crohn's disease, chronic pancreatitis, etc;
- Hepatocirrhosis or severe liver disease (defined as ascites, hepatic encepalopathy, coagulation disorder, hypoalbuminemia, Esophagus and fundus gastricus varication, persistent jaundice), known diseases of biliary tract (excluding Gilbert syndrome and Asymptomatic gallstone);
- Past or currently suffering from mandibular osteomyelitis or osteonecrosis, or any fracture within 6 months prior to first dosing; or suffering from acute tooth or mandibular disease that require tooth extracting, dental implanting or other invasive surgery; or had the above operation within 1-month before first dosing; or unhealing wound of oral surgery;
- HBsAg positive, or anti-HCV antibody positive, or anti-HIV antibody positive, or anti-Syphilis antibody positive;
- Prior malignancies (excluding the targeted breast cancer, basal cell carcinoma, or cervical cancer in situ) within 5 years (excluding completely resected Basal cell or squamous-cell carcinoma in situ, cervical carcinoma and Breast ductal carcinoma；
- A variety of diseases that affect the ability of the subject to sign informed consent or follow the steps of the study; or suffer from various physical or mental illnesses that the investigators consider to affect the subject's successful completion of the study or may interfere with the interpretation of the findings;
- Albumin-adjusted calcium≥2.0mmol/L, ≤2.9mmol/ L(Calcium supplements are not allowed within 8 hours before examination);
- Subjects with fracture high risk and requiring treatment;
- Has been selected for the study of other test devices or test drugs, or the duration of the clinical studies that have taken less than 30 days or 5 half-lives or biological effects, whichever is longer.
- Other situations which are not suitable for participation judged by the principal investigator (PI).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase I Trial of Evaluating the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of the Fully Human Monoclonal Antibody to RANKL (TK006) in Post-menopausal Women.
This is a single-center, open-label, dose-escalating study to evaluate the safety, pharmacokinetics, immunogenicity, and preliminary efficacy of single dose subcutaneous injection of a fully human monoclonal antibody of receptor activator for nuclear factor-κ B ligand (RNAKL) (code name: TK006) in postmenopausal women.
Read the detailed description
This is a phase I, open-label, single-dose, dose escalation study in postmenopausal women conducted at single center.
The objectives are to assess the safety and tolerability, effects on bone turnover measured by biochemical markers and bone density, and the pharmacokinetics and immunogenicity of a fully human monoclonal antibody of receptor activator for nuclear factor-κ B ligand (RNAKL), (code name: TK006).
Subjects would sequentially enroll in one of three cohorts. Subjects in the first cohort would receive a single 30-mg subcutaneous injection of TK006. If no safety signals are observed in the first cohort after 28 days, subjects would enroll in the second cohort and receive a single 60-mg subcutaneous injection of TK006. After an 28-day period for observation of safety of the second dose, subjects would enroll in the third cohort and receive a single 120-mg subcutaneous injection of TK006.
- Conditions
- Osteoporosis
- Being tested
- TK006
- Keywords
- RANKL, osteoporosis, bone resorption, post-menopausal women, TK006
- Medical subject headings
- Osteoporosis, Bone Resorption
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TK006Biological
Also called fully human monoclonal anti-RANKL antibody
Subcutaneous injection
| Study group | Role | What they receive |
|---|---|---|
| 30 mg single dose cohort | Experimental | Subjects would receive a 30 mg single dose of TK006. Receives: Biological: TK006 |
| 60 mg single dose cohort | Experimental | Subjects would receive a 60 mg single dose of TK006. Receives: Biological: TK006 |
| 120 mg single dose cohort | Experimental | Subjects would receive a 120 mg single dose of TK006. Receives: Biological: TK006 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of adverse events （AEs）
Include physical findings, changes in laboratory values, vital signs, and 12-lead electrocardiogram (ECG) data.
Measured: Up to 252 days.
Secondary outcomes (12)
Area under the plasma concentration-time curve from time zero to time 'last' where last is the last time point after administration [AUClast]
Calculated by the linear trapezoidal method.
Measured: Up to 252 days.
Area under the plasma concentration-time curve from time zero to infinity [AUC0-inf]
Calculated by the linear trapezoidal and extrapolation method.
Measured: Up to 252 days.
Maximum observed maximum plasma concentration [Cmax]
The maximum (or peak) serum concentration that TK006 achieves after the drug has been administrated and before the administration of a second dose.
Measured: Up to 252 days.
Time to reach the maximum observed plasma concentration [Tmax]
The time at which the Cmax is observed.
Measured: Up to 252 days.
Terminal elimination half-life[T1/2]
The time required to divide the plasma concentration by two after reaching pseudo-equilibrium, and not the time required to eliminate half the administered dose.
Measured: Up to 252 days.
Bioavailability corrected apparent volume of the central compartment cleared of drug per unit [Cl/F]
The apparent volume of the central compartment cleared of drug per unit time was estimated using the formula: Cl/F = Dose / AUC0-∞
Measured: Up to 252 days.
Bioavailability corrected apparent volume of distribution [Vd/F]
Apparent volume of distribution based on the terminal elimination phase.
Measured: Up to 252 days.
Serum type I collagen cross-link C telopeptide (sNTX)
Would be assessed at day1, 3, week 1, 2, 4, 8, 12, 16, 20, 24, 28, 32 and 36.
Measured: Up to 252 days.
serum bone alkaline phosphatase [bALP]
Would be assessed at week 1, 2, 4, 8, 12, 16, 20, 24, 28, 32 and 36.
Measured: Up to 252 days.
Intact Parathyroid Hormone (iPTH)
Would be assessed at day1, 3, week 1, 2, 4, 8, 12, 16, 20, 24, 28, 32 and 36.
Measured: Up to 252 days.
Bone density of lumbar vertebra and collum femoris
Assessed by Dual energy X-ray (DXA) bone density measurement at week 8,16, 24 and 36.
Measured: Up to 252 days.
anti-drug antibody [ADA]
Assessed at day 0（pre-dosing）, week 4, 12, 24 and 36.
Measured: Up to 252 days.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Aug 2017
- Study start7 Aug 2017
- Primary completion30 Dec 2018 (estimated)
- Study completion30 Dec 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for OsteoporosisStudies of the same condition, open and under way.
- 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Jiangsu T-Mab Biopharma Co.,Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jiang H Y, Study director, Jiangsu T-Mab Biopharma Co.,Ltd
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03242512
- Sponsor's protocol ID
- TK006-101
- Status last verified
- Mar 2018
- First submitted
- 3 Aug 2017
- Last updated
- 14 Mar 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Trial of Evaluating the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of the Fully Human Monoclonal Antibody to RANKL (TK006) in Post-menopausal Women.
- ClinicalTrials.gov ID
- NCT03242512
- Acronym / sponsor ID
- TK006-101
- Conditions
- Osteoporosis
- Keywords
- RANKL, osteoporosis, bone resorption, post-menopausal women, TK006
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- Jiangsu T-Mab Biopharma Co.,LtdIndustry (pharma, biotech, devices)
- Study start
- 7 Aug 2017 (actual)
- Primary completion
- 30 Dec 2018 (estimated)
- Study completion
- 30 Dec 2018 (estimated)
- First posted
- 8 Aug 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a single-center, open-label, dose-escalating study to evaluate the safety, pharmacokinetics, immunogenicity, and preliminary efficacy of single dose subcutaneous injection of a fully human monoclonal antibody of receptor activator for nuclear factor-κ B ligand (RNAKL) (code name: TK006) in postmenopausal women.
Detailed description
This is a phase I, open-label, single-dose, dose escalation study in postmenopausal women conducted at single center.
The objectives are to assess the safety and tolerability, effects on bone turnover measured by biochemical markers and bone density, and the pharmacokinetics and immunogenicity of a fully human monoclonal antibody of receptor activator for nuclear factor-κ B ligand (RNAKL), (code name: TK006).
Subjects would sequentially enroll in one of three cohorts. Subjects in the first cohort would receive a single 30-mg subcutaneous injection of TK006. If no safety signals are observed in the first cohort after 28 days, subjects would enroll in the second cohort and receive a single 60-mg subcutaneous injection of TK006. After an 28-day period for observation of safety of the second dose, subjects would enroll in the third cohort and receive a single 120-mg subcutaneous injection of TK006.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 30 mg single dose cohort | Experimental | Biological: TK006Subjects would receive a 30 mg single dose of TK006. |
| 60 mg single dose cohort | Experimental | Biological: TK006Subjects would receive a 60 mg single dose of TK006. |
| 120 mg single dose cohort | Experimental | Biological: TK006Subjects would receive a 120 mg single dose of TK006. |
Who may qualify
- Ages
- Up to 65 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- Subjects who provide informed consent voluntarily;
- Women who are postmenopausal defined as being amenorrheic for at least 24-month, and follicule-stimulating hormone (FSH)>40 U/L, estradiol (E2)<110pmol/L (or <30pg/mL) as well;
- ≤65 years old, with no restricted activity.
Key exclusion criteria (17 listed)
- Known hypersensitivity to similar medicines or other products derived from mammalian cells, or medical history of severe allergic to foods or medicines;
- Treatment with diphosphonate or fluoride, oestrogen, selective estrogen receptor modulators, calcitonin, parathyroid hormone, high dose Vitamin D (≥1000 IU/day), anabolic steroids, systemic glucocorticoids within 12-month before dosing, or administered with calcitriol within 6 months before dosing;
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) >2.0 times the upper limit of normal (ULN), or alkaline phosphatase (ALP)>1.5×ULN, or Total bilirubin (TBIL) >1.5×ULN, creatinine clearance rate<60 mL/min;
- Disorders that could affect the study outcomes, such as osteomalacia, dysostosis, Paget's disease, Cushing syndrome, hyperprolactinemia, rheumatoid arthritis, hyperparathyroidism, hypoparathyroidism, or other diseases that could affect bone metabolism;
- Hyperthyroidism or hypothyroidism, unless hypothyroidism patients are receiving regular treatment with thyroid hormone and:
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 |
|---|---|---|
| TK006Also: fully human monoclonal anti-RANKL antibodySubcutaneous injection | Biological | 120 mg single dose cohort, 30 mg single dose cohort, 60 mg single dose cohort |
Primary outcome
Incidence of adverse events （AEs）
Time frame: Up to 252 days.
Include physical findings, changes in laboratory values, vital signs, and 12-lead electrocardiogram (ECG) data.
12 secondary outcomes
Area under the plasma concentration-time curve from time zero to time 'last' where last is the last time point after administration [AUClast]
Time frame: Up to 252 days.
Area under the plasma concentration-time curve from time zero to infinity [AUC0-inf]
Time frame: Up to 252 days.
Maximum observed maximum plasma concentration [Cmax]
Time frame: Up to 252 days.
Time to reach the maximum observed plasma concentration [Tmax]
Time frame: Up to 252 days.
Terminal elimination half-life[T1/2]
Time frame: Up to 252 days.
Bioavailability corrected apparent volume of the central compartment cleared of drug per unit [Cl/F]
Time frame: Up to 252 days.
Bioavailability corrected apparent volume of distribution [Vd/F]
Time frame: Up to 252 days.
Serum type I collagen cross-link C telopeptide (sNTX)
Time frame: Up to 252 days.
serum bone alkaline phosphatase [bALP]
Time frame: Up to 252 days.
Intact Parathyroid Hormone (iPTH)
Time frame: Up to 252 days.
Bone density of lumbar vertebra and collum femoris
Time frame: Up to 252 days.
anti-drug antibody [ADA]
Time frame: Up to 252 days.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Mar 2018.
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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.
Jiang H Y study director
Jiangsu T-Mab Biopharma Co.,Ltd
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing TK006 in people with Osteoporosis, run by Jiangsu T-Mab Biopharma Co.,Ltd at 1 site in China.
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 3 inclusion and 17 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: status not confirmed, as of the sponsor's last update on 14 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. 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?
Results are not available in the source record.
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?
Incidence of adverse events （AEs） (time frame: Up to 252 days.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 14 Mar 2018.