Efficacy and Safety of QL1206 in the Treatment of Postmenopausal Osteoporosis With High Fracture Risk

A Twelve-month Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Study to Evaluate the Efficacy and Safety of QL1206 in Chinese Postmenopausal Women With Osteoporosis at High Risk of Fracture

A randomized, double-blind, two-group parallel, placebo-controlled clinical Phase III trial to compare the efficacy and safety of QL1206 and placebo in postmenopausal women with osteoporosis at high risk of fracture

Study Overview

• Status: Unknown
• Conditions: Postmenopausal Osteoporosis
• Intervention / Treatment: Drug: QL1206; Drug: Placebos

Detailed Description

This is a randomized, double-blind, two-group parallel, placebo-controlled clinical Phase III trial.

The primary objective is to evaluate the effect of QL1206 treatment compared with placebo in Chinese postmenopausal women with osteoporosis at high risk of fracture.

The secondary objective is to evaluate the clinical safety, immunogenicity and pharmacokinetic (PK) characteristics of QL1206 in women with osteoporosis at high risk of postmenopausal fracture

The exploratory purpose is to evaluate the effect of ADA on the characteristics of QL1206 PK and the relationship between QL1206 exposure and pharmacodynamic endpoints, efficacy and adverse events

Subjects would sequentially enrolled according to the protocol in one of two cohorts.Subjects would receive a single 60mg of QL1206 or placebo every 6 month for1 year(twice for one, subcutaneous injection) ,meanwhile taking 500 mg of calcium and 1000IU of vitamin D daily

• Study Type: Interventional
• Enrollment (Anticipated): 440
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China
      • Recruiting
      • Shanghai Sixth People's Hospital
      • Contact: Zhenlin Zhang
      • Principal Investigator: Zhenlin Zhang

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Subject is willing to provide written informed consent.
2. Ambulatory woman between the age of 50 and 85 years, inclusive.
3. The subject has a BMD absolute value consistent with a T-score<-2.5 and >-4.0 at either the lumbar spine or total hip
4. All subjects must have at least one of following additional the risk factors:history of fracture（after 40 years）,parental history of hip fracture, low Body mass index (BMI≤19kg/m^2), elderly (age≥65year)，current smoker
5. Postmenopausal defined as >2 years postmenopausal, which can be >2 years of spontaneous amenorrhea or >2 years post surgical bilateral oophorectomy.

Exclusion Criteria:

1. Bone/metabolic disease:a. Any metabolic bone disease, e.g., osteomalacia or osteogenesis imperfecta,which may interfere with the interpretation of the findings.

   b. Paget's disease c. Cushing's disease d. Hyperprolactinemia

2. Current hyperparathyroidism or hypoparathyroidism by medical record
3. Thyroid condition: Hyperthyroidism or hypothyroidism.

4. Rheumatoid arthritis

   -

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: QL1206; QL1206 injection (60mg:1ml) by subcutaneous injectionevery 6 month for two times. Dietary Supplement: Elemental Calcium Oral, at least 500 mg Dietary Supplement: Vitamin D Oral, 1000 IU	Drug: QL1206; subcutaneous injection of 60 mg（60mg:1ml）, Q6M, twice for one year. Dietary Supplement: Elemental Calcium Oral, at least 500 mg Dietary Supplement: Vitamin D Oral, 1000 IU; Other Names: Recombinant anti-RANKL human monoclonal antibody injection
Placebo Comparator: Placebo; placebo injection (1ml) by subcutaneous injectionevery 6 month for two times. Dietary Supplement: Elemental Calcium Oral, at least 500 mg Dietary Supplement: Vitamin D Oral, 1000 IU	Drug: Placebos; subcutaneous injection of（1ml）, Q6M, twice for one year. Dietary Supplement: Elemental Calcium Oral, at least 500 mg Dietary Supplement: Vitamin D Oral, 1000 IU

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change in Bone Mineral Density (BMD) at the Lumbar Spine from Baseline up to 12 months	Bone mineral density (BMD) is the amount of bone mineral in bone tissue. BMD scan was done using dual energy x-ray absorptiometry (DXA). It is used to identify osteoporosis, determine risk for fractures, and measure response to osteoporosis treatment. The percentage change from Baseline for BMD was calcuated as the value at the indicated time point minus the Baseline value multiplied by 100 and divided by the Baseline value. The analysis was performed by Analysis of Covariance (ANCOVA) model adjusted for treatment, region and Baseline BMD for the skeletal site under consideration as a continuous covariate for assessment. Region and treatment by region interaction was included in the model. Screening visit was considered as Baseline for BMD. For participants who withdrew early, the missing BMD assessments was estimated by the Last Observation Carried Forward (LOCF), provided the assessment was taken on or after at least three month on-therapy.	Baseline and Month 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change in BMD at the Lumbar Spine from Baseline up to 6 months	BMD is the amount of bone mineral in bone tissue. BMD scan was done using DXA. It is used to identify osteoporosis, determine risk for fractures, and measure response to osteoporosis treatment. The percentage change from Baseline for BMD was calculated as the value at the indicated time point minus the Baseline value multiplied by 100 and divided by the Baseline value	Baseline and Month 6
Percent change in BMD at the total hip, femoral neck and trochanter from Baseline up to 6 months and 12 months	Percent change in BMD at the total hip, femoral neck and trochanter as measured BMD is the amount of bone mineral in bone tissue. BMD scan was done using DXA. It is used to identify osteoporosis, determine risk for fractures, and measure response to osteoporosis treatment. The percentage change from Baseline for BMD was calculated as the value at the indicated time point minus the Baseline value multiplied by 100 and divided by the Baseline value.	Baseline 、 Month 6 and Month 12
Percent Change in Serum Carboxy-terminal Cross-linking Telopeptide of Type I Collagen (s-CTX) and Serum Procollagen Type I N Propeptideserum (s-PINP) from Baseline up to 6 months and 12 months	s-CTX is biomarker of bone resorption and formation. s-CTX was assessed during Screening, Month 6 and Month 12 in the Double-blind Treatment Phase. The value during Screening was considered as the Baseline value. Percent change from Baseline was assessed as the value at the indicated visit minus the Baseline value divided by the Baseline value x 100. s-PINP is biomarker of bone resorption and formation. s-PINP was assessed during Screening, Month 6 and Month 12 in the Double-blind Treatment Phase. The value during Screening was considered as the Baseline value. Percent change from Baseline was assessed as the value at the indicated visit minus the Baseline value divided by the Baseline value x 100	Baseline 、 Month 6 and Month 12
Adverse events and serious adverse events	Evaluation of the follwing parameters. Including adverse events(AEs), change in physical examination findings, change in vital signs, clinical laboratory testing for systemic safety,including liver function,renal function ,compelete blood count,and clinical chemistries	Baseline、 Month 1、 Month 3、 Month 6 、 Month 9 and Month 12
Immunogenicity	Anti-denosumab antibody formation was assessed. Binding antibody and neutralizing antibody assays were used to assess number of participants with anti-denosumab antibody.	Baseline、 Month 3、 Month 6 、 Month 9 and Month 12

Collaborators and Investigators

• Sponsor: Qilu Pharmaceutical Co., Ltd.
• Investigators: Principal Investigator: zhenlin zhang, Shanghai 6th People's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 5, 2019
• Primary Completion (Anticipated): August 31, 2021
• Study Completion (Anticipated): December 1, 2021

Study Registration Dates

• First Submitted: September 25, 2019
• First Submitted That Met QC Criteria: October 14, 2019
• First Posted (Actual): October 16, 2019

Study Record Updates

• Last Update Posted (Actual): November 6, 2019
• Last Update Submitted That Met QC Criteria: November 5, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Musculoskeletal Diseases; Bone Diseases; Bone Diseases, Metabolic; Osteoporosis; Osteoporosis, Postmenopausal
• Other Study ID Numbers: QL1206-004

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No