A Pilot Study of Technetium [99Tc] Methylene Diphosphonate in the Treatment of Psoriatic Arthritis

This study is aim to evaluate the efficacy and safety of technetium [99Tc] methylene diphosphonate (99Tc-MDP, trade name: Yunke) in the treatment of psoriatic arthritis.

Study Overview

• Status: Completed
• Conditions: Arthritis, Psoriatic
• Intervention / Treatment: Drug: 99Tc methylene diphosphonate

Detailed Description

This is a single-arm, open label, 24 weeks study. Patients with psoriatic arthritis get 99Tc-MDP 22mg (5.5mg/set, four sets) was injected intravenously once a day for 7 successive days, one course every 4 weeks until week 24.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Dongcheng
    • Beijing, Dongcheng, China, 100730
      • Peking Union Medical College Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 18-70 years of age;
• Clinical diagnosis of PsA according to the CASPAR classification criteria
• Active PsA at baseline defined as ≥ 3 tender joints and ≥ 3 swollen joints
• If subjects were taking csDMARDs, the doses of csDMARDs had to be stable for at least 4 weeks and had to remain the same during the trial

• The application of bDMARDs and tsDMARDs should meet the following requirements:

  1. Etanercept and its biological analogues: stop at least 4 weeks prior to their baseline visit;
  2. Other biological: stop at least 6 months prior to their baseline visit
  3. tsDMARDs: stop at least 8 weeks prior to their baseline visit
• If subjects were taking glucocorticoids, the doses of GC(prednisone < 10mg) had to be stable for at least 4 weeks and had to remain the same during the trial;
• Non steroidal anti-inflammatory drugs: if applied, the dose was stable one week prior to their baseline visit
• Negative pregnancy test for child-bearing women at screening and baseline
• Provide written informed consent

Exclusion Criteria:

• Patients with severe heart, liver, kidney and other important organ diseases
• Abnormal liver function (ALT or AST is 2 times higher than normal)
• White blood cell count less than 4,000/mm^3 (less than 4 X 10^9/L)
• Platelet count less than 100,000/mm^3 (less than 100 X 10^9/L)
• Serum creatinine more than or equal to 1.5 mg/dL (less than or equal to 132.6 μmol/L)
• Pregnancy or breastfeeding women
• Contraindications to 99Tc-MDP therapy and/or known hypersensitivity to 99Tc-MDP
• Participated in other drugs clinical trials within 4 weeks

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 99Tc methylene diphosphonate; 99Tc-MDP was applied as follows: for each course of treatment, 99Tc-MDP 22 mg (5.5mg/set, four sets) was injected intravenously once a day for 7 successive days, one course every 4 weeks until week 24.	Drug: 99Tc methylene diphosphonate; 22mg qd，Once a day for 7 consecutive days; Other Names: Yunke

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Patients Achieving DAS28-CRP<=3.2	DAS28-CRP: Disease Activity Score based on a count of swollen and tender joints (out of 28 joints), blood test measures of inflammation (CRP) and the patient's own assessment. Scores can take any positive value with a lower value indicating a better clinical condition. DAS28-CRP score of <=3.2 indicates low disease activity. <2.6 means disease remission	24 weeks
Proportion of Patients Achieving DAS28-ESR<=3.2	DAS28-ESR: Disease Activity Score based on a count of swollen and tender joints (out of 28 joints), blood test measures of inflammation (ESR) and the patient's own assessment. Scores can take any positive value with a lower value indicating a better clinical condition. DAS28-ESR score of <=3.2 indicates low disease activity. <2.6 means disease remission	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in PASI From Baseline From Baseline	Psoriasis Area and Severity Index	24 weeks
Change in HAQ-DI Score From Baseline	The HAQ-DI is a standardized measure of physical function in arthritis. The HAQ-DI questionnaire contains 20 items divided into 8 domains that measure: dressing and grooming, arising, eating, walking, hygiene, reach, grip, and common daily activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task were summed and averaged to provide an overall score ranging from 0 to 3, where 0 represents no disability and 3 very severe, high-dependency disability.	24 weeks
ACR20	The ACR is a standard criteria originally developed to measure the effectiveness of various arthritis medications or treatments in clinical trials for RA, but is also widely used in PsA. The ACR measures improvement in tender joint count (TJC) or swollen joint count (SJC), and improvement in at least 3 of the following 5 parameters: Patient Global Assessment (PtGA), Physician's Global Assessment of Disease Activity (PhGA), physical function (using HAQ-DI) and acute phase reactant (using CRP). ACR 20 response is achieved if ≥ 20% improvement in tender joint count (TJC) or swollen joint count (SJC) as well as a ≥ 20%/≥ 50%/≥ 70% improvement in ≥ 3 of the other 5 parameters.	12 weeks
Change in Disease Activity in Psoriatic Arthritis Score (DAPSA) Score From Baseline	Disease Activity in Psoriatic Arthritis Score (DAPSA) score is a the sum of swollen joint count (66 joints), tender joint count (68 joints), CRP (mg/dL), Patient's Assessment of Pain (on a 10-unit VAS;0=no pain, 10=worst possible pain), and Patient's Global Assessment of Disease Activity (arthritis, on a 10-unit VAS; 0 to 100 centimeter [cm] VAS, 0=excellent and 10=poor). Change from baseline in DAPSA measures the change in disease activity, where a negative change indicates an improvement and a positive change indicates worsening of disease activity.	24 weeks
Percentage of Participants in MDA	MDA for PsA was defined as fulfilling at least 5 of the following 7 criteria: TJC ≤ 1 (out of TJC68 assessed in this study), SJC ≤ 1 (out of SJC66 assessed in this study), PASI ≤ 1 or BSA ≤ 3; Patient's assessment of pain VAS ≤ 15, PtGA VAS ≤ 20, HAQ-DI score ≤ 0.5, and tender entheseal points ≤ 1	24 weeks
Change in Tender Joint Count (TJC) 68 from baseline	TJC is determined by physical examination of 68 joint counts that are assessed for tenderness.	12 weeks and 24 weeks
Change in Swollen Joint Count (SJC) 66 from baseline	SJC is determined by physical examination of 66 joint counts that are classified as either swollen or not swollen.	12 weeks and 24 weeks

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital
• Collaborators: Chengdu Yunke Pharmaceutical Co., Ltd.

Publications and helpful links

General Publications

• Shen S, Wang W, Yang C, Xu B, Zeng L, Qian Y. Effect of technetium-99 conjugated with methylene diphosphonate (99 Tc-MDP) on OPG/RANKL/RANK system in vitro. J Oral Pathol Med. 2019 Feb;48(2):129-135. doi: 10.1111/jop.12801. Epub 2018 Dec 9.
• Mu R, Liang J, Sun L, Zhang Z, Liu X, Huang C, Zhu P, Zuo X, Gu J, Li X, Li X, Liu Y, Feng P, Li Z. A randomized multicenter clinical trial of 99 Tc-methylene diphosphonate in treatment of rheumatoid arthritis. Int J Rheum Dis. 2018 Jan;21(1):161-169. doi: 10.1111/1756-185X.12934. Epub 2017 Feb 3.
• Fu Q, Feng P, Sun LY, Zuo XX, Zhao DB, He DY, Wu HX, Zhang W, Zhang W, Du F, Bao CD. A double-blind, double-dummy, randomized controlled, multicenter trial of 99Tc-methylene diphosphonate in patients with moderate to severe rheumatoid arthritis. Chin Med J (Engl). 2021 May 19;134(12):1457-1464. doi: 10.1097/CM9.0000000000001527.
• Su D, Shen M, Gu B, Wang X, Wang D, Li X, Sun L. (99) Tc-methylene diphosphonate improves rheumatoid arthritis disease activity by increasing the frequency of peripheral gammadelta T cells and CD4(+) CD25(+) Foxp3(+) Tregs. Int J Rheum Dis. 2016 Jun;19(6):586-93. doi: 10.1111/1756-185X.12292. Epub 2014 Jan 28.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2019
• Primary Completion (Actual): July 1, 2021
• Study Completion (Actual): July 1, 2021

Study Registration Dates

• First Submitted: August 3, 2021
• First Submitted That Met QC Criteria: August 3, 2021
• First Posted (Actual): August 11, 2021

Study Record Updates

• Last Update Posted (Actual): August 11, 2021
• Last Update Submitted That Met QC Criteria: August 3, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: 99Tc-MDP
• Additional Relevant MeSH Terms: Skin Diseases; Joint Diseases; Musculoskeletal Diseases; Skin Diseases, Papulosquamous; Spinal Diseases; Bone Diseases; Spondylarthropathies; Spondylarthritis; Spondylitis; Psoriasis; Arthritis; Arthritis, Psoriatic; Physiological Effects of Drugs; Bone Density Conservation Agents; Methylene diphosphonate; Diphosphonates
• Other Study ID Numbers: YK1901PsA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All of the individual participant data collected during the trial, after deidentification.
• IPD Sharing Time Frame: Beginning 3 months and ending 5 years after article publication
• IPD Sharing Access Criteria: Researchers who provide a methodologically sound proposal. Proposals should be directed to lpumch@126.com. To gain access, data requestors will need to sign a data access agreement
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

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