Phase 1 Study to Compare CMAB807 Injection to Prolia® in Healthy Volunteers

• ClinicalTrials.gov Identifier: NCT03925051
• Recruitment Status: Completed
• First Posted: April 23, 2019
• Last Update Posted: October 14, 2020
• Sponsor: Shanghai Biomabs Pharmaceutical Co., Ltd.
• Information provided by (Responsible Party): Shanghai Biomabs Pharmaceutical Co., Ltd.

Study Description

Brief Summary:

CMAB807 is a human monoclonal antibody targeting the key bone resorption mediator RANKL. The drug is administered via subcutaneous injection once six months and is approved for various indications, including the treatment of postmenopausal women with osteoporosis at increased/high risk of fracture. This phase 1 clincical study investigates the pharmacokinetics, safety and immnogenicity of CMAB807,compared to prolia®, in healthy Chinese male subjects.

Condition or disease	Intervention/treatment	Phase
Postmenopausal Osteoporosis	Drug: Prolia®; Drug: CMAB807	Phase 1

Detailed Description:

This is a phase 1 single center, randomized, double-masked, parallel-group clinical trial. The primary objective is to assess the pharmacokinetics similarity of single and subcutaneous injection of CMAB807 injection or Prolia® in health volunteers. The secondary objectives are to assess the clinical safety and immnogenicity similarity of single and subcutaneous injection of CMAB807 or Prolia® in healty volunteers. Meanwhile, exploring the pharmacodynamic similarities of CMAB807 and Prolia®.

Subjects will receive a single 60mg of CMAB807 or Prolia® through subcutaneous injection.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 132 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Randomized, Double-masked, Parallel-group
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: subjects, investigator, sponsor
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-masked, Parallel-group Study, to Compare Pharmacokinetics, Safety and Immunogenicity of CMAB807 Injection Versus Prolia® in Healthy Chinese Male Subjects.
• Actual Study Start Date: July 1, 2019
• Actual Primary Completion Date: March 21, 2020
• Actual Study Completion Date: June 18, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: CMAB807; 60mg by subcutaneous injection once on the first day.	Drug: CMAB807; human monoclonal antibody targeting RANKL.; Other Name: Denosumab Injection
Active Comparator: Prolia®; 60mg by subcutaneous injection once on the first day.	Drug: Prolia®; mAb targeting RANKL. human monoclonal antibody targeting RANKL.; Other Name: Denosumab Injection

Outcome Measures

Primary Outcome Measures :

1. AUC0-t [ Time Frame: 0~126 day ]
   Area Under Curve(AUC)0-t
2. Cmax [ Time Frame: 0~126 day ]
   Maximum Concentration

Secondary Outcome Measures :

1. Incidence of Adverse Event [ Time Frame: 0~126 day ]
   measured by common terminology criteria for adverse events grading
2. Antidrug Antibody [ Time Frame: 0~126 day ]
   Percentage of Subjects Positive for Antidrug Antibody
3. Serum type 1 C-telopeptide(CTX1) [ Time Frame: 0~126 day ]
   explore the pharmacodynamic profile by detect the serum concentration of CTX1

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Fully understand and voluntary sign the informed consent form,and be able to complete the study according to the protocol;
• 18 years ≤ age ≤65 years;
• Physical examination, vital signs, clinical laboratory examination and various examinations are normal or abnormal without clinical significance;
• Agree to take effective contraceptive measures throughout the study period (including not limited to: physical contraception, hormonal drugs of pregnancy, surgery, abstinence, etc.,) until at least 10 months after the last study is administered;
• Body weight ≥50 kg, 19kg/m2≤BMI≤26kg/m2;
• Serum calcium level between 2.15~2.55mmol/L（including the boundary value）;
• Normal or clinically acceptable electrocardiogram (12-lead ECG), QTcB<450msec.

Exclusion Criteria:

• Drink 14 units of alcohol per week within 3 months prior to administration, or take any alcohol substance within 48 hours before subcutaneous injection;
• Substance abuse within 5 years before subcutaneous injection;
• Smoke more than 5 cigarettes per day or the same amount of tobacco within 3 months before subcutaneous injection;
• Allergic constitution;
• Drink excessive amounts of tea, coffee or caffeinated beverages within 30 days before subcutaneous injection;
• Use any prescription, over-the-counter, vitamin or herbal medicine within 30 days before subcutaneous injection;
• Bone surgery was performed within 30 days before administration;
• History of osteomyelitis or osteonecrosis of the jaw;
• Inflammation or abnormalities in or around the site of administration;
• Needle or blood sickness;
• Dental disease or jaw disease requiring oral surgery, dental surgery; or plan to have dental surgery during the study;
• Received the study drug(including Xgeva and Prolia), or participated in a clinical trial within 3 months prior to administration；
• Received living viraL vaccine within 3 months prior to administration;
• Blood donation or blood loss >400ml within 3 months prior to administration;
• Hepatitis B surface antigen was positive, and/or hepatitis C antibody was positive;
• The HIV antibody test was not negative;
• Syphilitic test was positive;
• Drug was detected in the urine;
• Hyperparathyroidism, hypothyroidism, rheumatoid arthritis, Ankylosing Spondylitis, osteomalacia, Paget's disease, or fracture within 6 months;
• History of severe lumbar disc herniation;
• Insanity or legal problem are exist;
• Plan to engage in strenuous physical labor or exercise during the study;
• Other conditions that made it difficult to participate the study.

Contacts and Locations

Locations

China, Shanghai

Zhongshan Hospital

Shanghai, Shanghai, China, 200032

Sponsors and Collaborators

Shanghai Biomabs Pharmaceutical Co., Ltd.

Investigators

• Study Chair: xuening li, PhD; Fudan University

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Chen H, Chen W, Yuan F, Guo Q, Zhang X, Wang C, Li X. Pharmacokinetics, Pharmacodynamics, Safety and Immunogenicity of CMAB807, a New Denosumab Biosimilar, in Healthy Chinese Subjects. Front Pharmacol. 2022 Jan 24;13:821944. doi: 10.3389/fphar.2022.821944. eCollection 2022.

• Responsible Party: Shanghai Biomabs Pharmaceutical Co., Ltd.
• ClinicalTrials.gov Identifier: NCT03925051
• Other Study ID Numbers: CMAB807-I-001
• First Posted: April 23, 2019
• Last Update Posted: October 14, 2020
• Last Verified: October 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:

Osteoporosis; Osteoporosis, Postmenopausal; Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Denosumab; Bone Density Conservation Agents; Physiological Effects of Drugs