MPA AUC Monitoring in Patients Receiving MMF for Diffuse Cutaneous or Pulmonary Involvement in Systemic Sclerosis

Systemic Sclerosis Clinical Trial

— SCLERAMAC  

Official title:

Prospective Study to Investigate the Relevance of Monitoring Area Under the Curve of Mycophenolic Acid in Patients Receiving Mycophenolate Mofetil to Treat a Diffuse Cutaneous or a Pulmonary Involvement of Systemic Sclerosis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04244916
• Other study ID #: APHP190933
• Status: Recruiting
• Start date: May 25, 2020
• Est. completion date: September 25, 2023

Study information

• Verified date: November 2021
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Paul LEGENDRE, MD
• Phone: (33) 1.58.41.29.30
• Email: paul.legendre[@]aphp.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

To define a target value of AUC MPA to improve the modified Rodnan score and / or respiratory impairment (DLCO or FVC) at one year in patients receiving MMF for the treatment of diffuse cutaneous or interstitial lung damage of systemic sclerosis.

Description:

In the treatment of autoimmune diseases, MMF is almost always prescribed at a fixed dose, regardless of AUC, or based on the target of AUC determined for organ transplantation. One study looked at determining an "effective" AUC threshold in systemic lupus erythematosus, which appears to be 35mg / h / l. This was also done for ANCA vasculitis.

We therefore conducted this study to determine a correlation between AUC MPA and the effectiveness of MMF in systemic sclerosis.

Prospective, observational, open study.

Main objective: define a target value of AUC MPA to improve the modified Rodnan score and / or respiratory impairment (DLCO or FVC) at one year in patients receiving MMF for the treatment of diffuse skin involvement or pulmonary function in systemic sclerosis.

The main endpoint will be evaluated on the evolution of the modified Rodnan score at 1 year after the initiation of MMF and / or the evolution of FVC and DLCO at 1 year after the initiation of MMF.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: September 25, 2023
• Est. primary completion date: May 25, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Systemic sclerosis meeting the ACR / EULAR criteria of 2013

• Equal or more than 18 years old, able to freely consent to study

• In patients treated for skin damage:

• Diffuse skin sclerosis (rising above the elbows and / or knees)

• First clinical sign of systemic sclerosis outside of Raynaud's phenomenon going back less than three years

• Failure to take other concomitant immunosuppressive treatments or in the last 3 months except corticosteroids.

• In patients treated for lung damage:

• Interstitial lung damage identified on chest CT, chest x-ray

• Any duration of progression of systemic scleroderma

• Prescription of MMF in first line or in relay of a treatment with Cyclophosphamide.

• Absence of biotherapy in the last 6 months.

Exclusion Criteria:

-

Related Conditions & MeSH terms

• Scleroderma, Diffuse
• Scleroderma, Systemic
• Sclerosis
• Systemic Sclerosis

Intervention

Biological:
• AUC of MPA measure
Plasmatic AUC determination of MPA requires 3 blood punctures at H0, H30 and H2. These punctures will be made at inclusion after 6 weeks, 12 weeks, 6 months and one year.

Locations

Country	Name	City	State
France	Cochin hospital, AP-HP	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

References & Publications (3)

Chaigne B, Gatault P, Darrouzain F, Barbet C, Degenne D, François M, Szymanski P, Rabot N, Golea G, Diot E, Maillot F, Lebranchu Y, Nivet H, Paintaud G, Halimi JM, Guillevin L, Büchler M. Mycophenolate mofetil in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis: a prospective pharmacokinetics and clinical study. Clin Exp Immunol. 2014 May;176(2):172-9. doi: 10.1111/cei.12246. — View Citation

van Gelder T, Le Meur Y, Shaw LM, Oellerich M, DeNofrio D, Holt C, Holt DW, Kaplan B, Kuypers D, Meiser B, Toenshoff B, Mamelok RD. Therapeutic drug monitoring of mycophenolate mofetil in transplantation. Ther Drug Monit. 2006 Apr;28(2):145-54. Review. — View Citation

Zahr N, Arnaud L, Marquet P, Haroche J, Costedoat-Chalumeau N, Hulot JS, Funck-Brentano C, Piette JC, Amoura Z. Mycophenolic acid area under the curve correlates with disease activity in lupus patients treated with mycophenolate mofetil. Arthritis Rheum. 2010 Jul;62(7):2047-54. doi: 10.1002/art.27495. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Skin efficacy	Modified Rodnan skin score (mRSS) : min 0 max 51. A diminution in the mRSS of more than 25% from the initial value was considered as improved. On the contrary, an increase in the mRSS over 25% was considered as deteriorated. All other variations of mRSS were classified as stable. Minimal clinically important difference was also tested (worsening of mRSS = 4.7).	1 year
Secondary	Pulmonary efficacy.1	Modification in FVC	1 year
Secondary	Pulmonary efficacy.2	Modification in DLCO	6 months and 1 year