Rapamycin Plus Methylprednisolone Versus Methylprednisolone Alone in Active, Moderate-to-severe Graves' Orbitopathy.

NCT05532072 | Unknown Early Phase 1 FDA Drug

• 1 other identifier: XJTU1AF2021CRF-004
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a randomized, controlled, multi-center clinical study, the purpose is to evaluate the efficacy and safety of rapamycin combined with methylprednisolone in the treatment of moderate to severe active GO. GO patients with moderate to severe activity were selected as the research objects, and the screening period was 1 week. Eligible and well-informed subjects were randomly assigned 1:1 to the experimental group (rapamycin + methylprednisolone) or the control group (methylprednisolone group). The control group was given methylprednisolone pulse 500 mg/time once a week for 6 weeks + 250 mg/time once a week for 6 weeks, and the experimental group was given rapamycin 2 mg/day orally for 24 weeks on the basis of methylprednisolone pulse therapy. The follow-up period was from 25th to 36th week. Before treatment, 1 week after treatment, 6 weeks, 12 weeks, 24 weeks, and 36 weeks, visits were conducted to evaluate the improvement and safety evaluation of patients' GO eye activity, severity, and quality of life. At the end of the 1st week and the 12th week, the blood concentration of rapamycin was measured.

Conditions

Graves Ophthalmopathy

Outcome Measures

Primary Outcomes (2)

• Number of participants who responded to treatment as assessed by CAS score, eye cleft width, eye movement, etc.

  To assess the number of treatment-responsive participants with rapamycin 2 mg/day orally for 24 weeks in combination with pulsed methylprednisolone and pulsed methylprednisolone alone for moderately to severely active GO.

  24 weeks

• Number of participants with treatment-related adverse events assessed by physical examination, electrocardiogram, and serum biochemical markers.

  To evaluate the number of participants for treatment-related adverse effects of rapamycin 2 mg/day orally for 24 weeks in combination with pulsed methylprednisolone and pulsed methylprednisolone alone in the treatment of moderately to severely active GO.

  24 weeks

Secondary Outcomes (10)

• Number of participants who responded to treatment as assessed by CAS score, eye cleft width, eye movement, etc.

  36 weeks

• Number of participants with disease recurrence as assessed by CAS score, eye movement, visual acuity, diplopia, etc.

  36 weeks

• Antibody titers

  24 weeks

• Antibody titers

  36 weeks

• GO-QoL Score

  24 weeks

Study Arms (2)

The group of Meprednone combined with Rapamycin

EXPERIMENTAL

The specific dose of methylprednisolone pulse therapy is 500mg / week \* 6 + 250mg / week \* 6. RAPA has rich experience in the application of renal transplantation, and the recommended maintenance amount for renal transplant patients is 2 mg / day. The efficacy benefits of doses above 2 mg are unclear, and the overall safety of Rapa 2 mg is better than that of patients taking Rapa 5 mg daily. Therefore, based on the clinical experience and clinical research data of RAPA, we would select the dose of Rapamycin as 2mg / day. The experimental group received rapamycin 2 mg/day orally for 24 weeks on the basis of methylprednisolone pulse therapy, and monitor the blood concentration of Rapa at the end of the first week and the end of the 12th week.

Drug: Rapamycin; Drug: Methylprednisolone

The group of Meprednone alone

OTHER

The specific dose of methylprednisolone pulse therapy is 500mg / week \* 6 + 250mg / week \* 6. The effect of methylprednisolone pulse therapy on moderate and severe active Tao has been widely verified in clinical work. EUGOGO will take methylprednisolone pulse therapy as the first-line treatment of moderate and severe active Tao in 2020.

Drug: Methylprednisolone

Interventions

Rapamycin DRUG

Rapamycin plus Methylprednisolone

Also known as: Sirolimus

The group of Meprednone combined with Rapamycin

Methylprednisolone DRUG

Methylprednisolone Alone

The group of Meprednone alone; The group of Meprednone combined with Rapamycin

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• )18-70 years old 2)Clinically diagnosed GO (a. Moderate-severe, b. Active stage)
• Moderate-severe( CSS Grading Standards for EUGOGO 2021)
• Active stage (CAS) ≥ 3

You may not qualify if:

• Sight-threatening GO
• There are obvious abnormalities in laboratory tests: liver damage: ALT and AST ≥ 3 times the upper limit of normal values; kidney damage: serum creatinine ≥ 1.5\*ULN; blood routine: hemoglobin \< 9g/dl, white blood cell count \< 3000/µl or Platelets \< 100,000/µl; blood lipids: total cholesterol \> 300 mg/dl or triglycerides \> 400 mg/dl after lipid-lowering therapy;
• The patient developed an infection during treatment, requiring intravenous antibiotics, and did not show clinical improvement within 5 days;
• The subject has a systemic allergic reaction to rapamycin or methylprednisolone;
• The subject is pregnant during the test;
• The patient requests to withdraw from the researcher;
• Investigators believe that they cannot continue to participate in the experiment.

Sponsors & Collaborators

• First Affiliated Hospital Xi'an Jiaotong University: lead
• Beijing Tongren Hospital: collaborator
• Cheloo Hospital (Qingdao), Shandong University: collaborator
• Jiangsu Province Hospital with Integration of Chinese and Western Medicine: collaborator
• Nanjing First Hospital, Nanjing Medical University: collaborator
• Zhejiang Provincial People's Hospital: collaborator
• Southern Medical University, China: collaborator
• People's Hospital of Xinjiang Uygur Autonomous Region: collaborator
• The Second Affiliated Hospital of Air Force Military Medical University: collaborator

Study Sites (1)

First Affiliated Hospital of Xian Jiaotong University

Xi'an, Shaanxi, 710061, China

Location

MeSH Terms

Conditions

Graves Ophthalmopathy

Interventions

Sirolimus; Methylprednisolone

Condition Hierarchy (Ancestors)

Eye Diseases, Hereditary; Eye Diseases; Graves Disease; Exophthalmos; Orbital Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Goiter; Thyroid Diseases; Endocrine System Diseases; Hyperthyroidism; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Bingyin Shi

  First Affiliated Hospital Xi'an Jiaotong University

  STUDY CHAIR

Central Study Contacts

Yue Wang

CONTACT

0086-13630289316; shelly1021@126.com

Ling Wang

CONTACT

18160138359; wlstriver@163.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 19, 2022
• First Posted: September 8, 2022
• Study Start: September 1, 2022
• Primary Completion: September 1, 2023
• Study Completion: September 1, 2023
• Last Updated: September 8, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, CSR
• Time Frame: 2023
• Access Criteria: Accepted by author

Locations

CN (1)