Assessment of Anti-RANKL Antibody in Post-menopausal Women

NCT03242512 | Unknown Phase 1

• 1 other identifier: TK006-101
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Osteoporosis

Keywords

RANKL; osteoporosis; bone resorption; post-menopausal women; TK006

Outcome Measures

Primary Outcomes (1)

• Incidence of adverse events （AEs）

  Include physical findings, changes in laboratory values, vital signs, and 12-lead electrocardiogram (ECG) data.

  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]

  Up to 252 days.

• Area under the plasma concentration-time curve from time zero to infinity [AUC0-inf]

  Up to 252 days.

• Maximum observed maximum plasma concentration [Cmax]

  Up to 252 days.

• Time to reach the maximum observed plasma concentration [Tmax]

  Up to 252 days.

• Terminal elimination half-life[T1/2]

  Up to 252 days.

Study Arms (3)

30 mg single dose cohort

EXPERIMENTAL

Subjects would receive a 30 mg single dose of TK006.

Biological: TK006

60 mg single dose cohort

EXPERIMENTAL

Subjects would receive a 60 mg single dose of TK006.

Biological: TK006

120 mg single dose cohort

EXPERIMENTAL

Subjects would receive a 120 mg single dose of TK006.

Biological: TK006

Interventions

TK006 BIOLOGICAL

Subcutaneous injection

Also known as: fully human monoclonal anti-RANKL antibody

120 mg single dose cohort; 30 mg single dose cohort; 60 mg single dose cohort

Eligibility Criteria

• Age: Up to 65 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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
• 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;

Sponsors & Collaborators

• Jiangsu T-Mab Biopharma Co.,Ltd: lead

Study Sites (1)

Peking Union Medical College Hospital

Beijing, Beijing Municipality, China

Location

MeSH Terms

Conditions

Osteoporosis; Bone Resorption

Condition Hierarchy (Ancestors)

Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Jiang H Y

  Jiangsu T-Mab Biopharma Co.,Ltd

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 3, 2017
• First Posted: August 8, 2017
• Study Start: August 7, 2017
• Primary Completion: December 30, 2018
• Study Completion: December 30, 2018
• Last Updated: March 14, 2018

Record last verified: 2018-03

Locations

CN (1)