Efficacy and Safety of Thalidomide for Pediatric PFAPA Syndrome

Efficacy and Safety of Thalidomide in Treating Pediatric PFAPA Syndrome: A Multicenter Randomized Controlled Trial

The goal of this clinical trial is to evaluate the efficacy and safety of thalidomide in the treatment of children with Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Adenitis (PFAPA) syndrome. The study focuses on children diagnosed with PFAPA syndrome. The main questions it aims to answer are:

Can thalidomide significantly reduce the frequency of febrile episodes in children with PFAPA syndrome? What is the safety profile and tolerability of thalidomide in this pediatric population? Researchers will compare the thalidomide group to a colchicine group to see if thalidomide is more effective in controlling recurrent fever and associated symptoms.

Participants will:

Take the assigned medication (thalidomide or colchicine) daily for a duration of 6 months.

Attend follow-up visits every 4 weeks at the clinic. Maintain a diary to record the frequency of fever episodes and any other clinical symptoms.

Undergo safety assessments and physical examinations during each scheduled visit.

Study Overview

• Status: Not yet recruiting
• Conditions: Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Adenitis Syndrome
• Intervention / Treatment: Drug: Thalidomide (50mg); Drug: Colchicine

• Study Type: Interventional
• Enrollment (Estimated): 106
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Chang Liu; Phone Number: 86+13736320153; Email: 1712400881@qq.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Meet the 2019 Eurofever or 2020 CARRA diagnostic criteria for PFAPA syndrome.
2. Aged 3 to 18 years (inclusive) at the time of screening.
3. Have experienced at least 3 febrile episodes within the past six months.
4. History of responsiveness to glucocorticoid treatment during at least 3 previous episodes, but with continued recurrence. (Responsiveness is defined as normalization of body temperature within 24 hours after a maximum dose of 2 mg/kg [up to 60 mg] administered as a single or two divided doses).

Exclusion Criteria:

1.Diagnosis of monogenic or other polygenic periodic fever syndromes. 2.Presence of immunodeficiency or neoplastic diseases. 3.Active bacterial, fungal, or viral infection during the screening period. 4.Prior treatment with immunosuppressive agents. 5.Prior use of thalidomide or colchicine. 6.Laboratory parameters at screening that meet any of the following (based on the most recent test result at the study hospital prior to the first dose):

1. White Blood Cell (WBC) count < 4 × 10⁹/L, Hemoglobin (HGB) < 100 g/L, or Platelet (PLT) count < 100 × 10⁹/L.
2. Serum Alanine Aminotransferase (ALT) > 2 times the Upper Limit of Normal (ULN).
3. Glomerular Filtration Rate (GFR/CCR) < 60 mL/min/1.73m².

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Thalidomide Group; Patients in this group will receive oral thalidomide treatment for 12 months.	Drug: Thalidomide (50mg); The starting dose of thalidomide is 1 mg/kg/day, administered orally before bedtime. If febrile episodes persist during treatment, the dosage will be increased starting the day after the next fever (maximum dose not to exceed 2 mg/kg/day, with a maximum total dose of 100 mg/day).
Active Comparator: Colchicine Group; Patients in this group will receive oral colchicine treatment for 12 months.	Drug: Colchicine; The starting dose of colchicine is 0.5 mg/day administered orally. If febrile episodes persist during treatment, the dosage will be increased starting the day after the next fever (maximum dose not to exceed 1.25 mg/day).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Participants Achieving Complete Remission at 6 Months	Complete remission is defined as the total absence of febrile episodes (zero attacks) during the treatment period.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Remission Rate at Multiple Time Points	Proportion of participants with zero febrile episodes.	3 months
Complete Remission Rate at Multiple Time Points	Proportion of participants with zero febrile episodes.	9 months
Complete Remission Rate at Multiple Time Points	Proportion of participants with zero febrile episodes.	12 months
Partial Remission Rate	Proportion of participants achieving a reduction in the frequency of febrile episodes compared to baseline.	3 months
Recurrence Rate Post-discontinuation	Proportion of participants experiencing a relapse of symptoms after stopping the medication.	6 months post-treatment
Recurrence Rate Post-discontinuation	Proportion of participants experiencing a relapse of symptoms after stopping the medication.	12 months post-treatment
Change in Growth Parameters (Z-scores)	Changes in Height-for-age Z-score (HAZ) and Weight-for-age Z-score (WAZ).	6 months
Change in Growth Parameters (Z-scores)	Changes in Height-for-age Z-score (HAZ) and Weight-for-age Z-score (WAZ).	12 months
Change in Inflammatory Markers	Changes in CRP, ESR, SAA, and cytokine levels.	6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Adverse Events	Percentage of participants experiencing diarrhea, abdominal pain, nausea, liver function abnormality, somnolence, constipation, rash, or peripheral neuropathy (numbness).	1 month
Incidence of Adverse Events	Percentage of participants experiencing diarrhea, abdominal pain, nausea, liver function abnormality, somnolence, constipation, rash, or peripheral neuropathy (numbness).	6 months
Incidence of Adverse Events	Percentage of participants experiencing diarrhea, abdominal pain, nausea, liver function abnormality, somnolence, constipation, rash, or peripheral neuropathy (numbness).	12 months
Quality of Life (PedsQL-SF15)	Change in Pediatric Quality of Life Inventory Short Form 15 scores.	6 months
Quality of Life (PedsQL-SF15)	Change in Pediatric Quality of Life Inventory Short Form 15 scores.	12 months

Collaborators and Investigators

• Sponsor: Wenjie Zheng
• Collaborators: Children's Hospital of Soochow University; Nanjing Children's Hospital; The First Affiliated Hospital of Xiamen University; Tianjin Children's Hospital; Ningbo Women & Children's Hospital; Jinan children's hospital; Jiangxi Children's Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): March 31, 2027
• Study Completion (Estimated): March 30, 2028

Study Registration Dates

• First Submitted: March 9, 2026
• First Submitted That Met QC Criteria: March 12, 2026
• First Posted (Actual): March 17, 2026

Study Record Updates

• Last Update Posted (Actual): March 17, 2026
• Last Update Submitted That Met QC Criteria: March 12, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mouth Diseases; Stomatognathic Diseases; Genetic Diseases, Inborn; Respiratory Tract Infections; Infections; Respiratory Tract Diseases; Skin Diseases; Otorhinolaryngologic Diseases; Skin Diseases, Genetic; Pharyngeal Diseases; Stomatitis; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin and Connective Tissue Diseases; Hereditary Autoinflammatory Diseases; Pharyngitis; Stomatitis, Aphthous; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Carboxylic Acids; Alkaloids; Piperidines; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Piperidones; Isoindoles; Thalidomide; Colchicine
• Other Study ID Numbers: SAHoWMU-CR2026-06-102

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Data contains sensitive patient information and is restricted by institutional policy.

Drug and device information, study documents

• 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