A study to investigate whether mycophenolate mofetil is more effective than azathioprine in patients with autoimmune hepatitis

• Register: EUCTR
• Last refreshed on: 5 December 2016
• Main ID: EUCTR2016-001038-91-NL
• Date of registration: 25/10/2016
• Prospective Registration: Yes
• Primary sponsor: Leiden university medical centre
• Public title: A study to investigate whether mycophenolate mofetil is more effective than azathioprine in patients with autoimmune hepatitis
• Scientific title: A randomised, open-label clinical trial assessing the efficacy and safety of mycophenolate mofetil versus azathioprine for induction of remission in treatment naive autoimmune hepatitis - CAMARO
• Date of first enrolment: 18/11/2016
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-001038-91
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes

Countries of recruitment

Netherlands

Contacts

• Name: Simon Pape
• Affiliation: Radboud university medical centre

• Name: Simon Pape
• Affiliation: Radboud university medical centre

Key inclusion & exclusion criteria

Inclusion criteria:
1. Probable or definite diagnosis of autoimmune hepatitis according to the International Autoimmune Hepatitis Study Group criteria (table 2) 9:
• Definite autoimmune hepatitis: = 7
• Probable autoimmune hepatitis = 6
2. First presentation of AIH requiring treatment according to the current EASL guidelines
3. Age = 18 years
4. Must provide informed consent and agree to comply with the trial protocol

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 60
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 16

Exclusion criteria:
1. Overlap syndrome with PSC or PBC (Paris criteria 29, strong positive AMA, past liver biopsy or cholangiographic findings compatible with PBC or PSC).

2. Presence of clinical significant hepatic decompensation including:

• History of liver transplantation, current active placement on a liver transplant waiting list.
• Portal hypertension with complications including: poorly controlled or diuretic resistant ascites, history of variceal bleeding or related therapeutic interventions (e.g. variceal banding, transjugular intrahepatic portosystemic shunts) or hepatic encephalopathy.
• Cirrhosis with complications, including history or presence of: spontaneous bacterial peritonitis, hepatocellular carcinoma, hepatorenal syndrome
a. N.B. cirrhosis without complications as mentioned above, is not an exclusion criterion

3. Current treatment with predniso(lo)ne and/or immunosuppressive medication for an indication other than autoimmune hepatitis

4. Current systemic infection

5. Other clinically significant medical conditions that could interfere with the trial

6. If female of childbearing potential: known pregnancy, or unwilling to practice anticontraceptive measures.

7. History of noncompliance with medical regimens, or patients who are considered to be potentially unreliable or unable to participate

8. Mental instability or incompetence, such that the validity of informed consent or compliance with the trial is uncertain



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Autoimmune hepatitis

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Intervention(s)

Trade Name: mycophenolate mofeti
Product Name: mycophenolate mofetil
Pharmaceutical Form: Capsule
INN or Proposed INN: mycophenolate mofetil
CAS Number: 128794-94-5
Other descriptive name: MYCOPHENOLATE MOFETIL
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: 500-2000

Trade Name: azathioprine
Product Name: azathioprine
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: azathioprine
CAS Number: 446-86-6
Other descriptive name: AZATHIOPRINE
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: 50-100

Trade Name: prednisolone
Product Name: prednisolone
Pharmaceutical Form: Tablet
INN or Proposed INN: Prednisolone
CAS Number: 1715-33-9
Other descriptive name: PREDNISOLONE SODIUM SUCCINATE
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: 5-40

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: 24 weeks

Primary end point(s): The percentage of patients in remission, defined as normalization of serum ALT and IgG levels after 24 weeks of treatment, per treatment group.

Main Objective: To assess the efficacy and safety of mycophenolate mofetil as induction therapy in patients with treatment naive autoimmune hepatitis.

Secondary Objective: A. Biochemical remission at 24 weeks and at anytime
B. Time to biochemical remission
C. Partial remission, defined as ALT and AST serum levels >1x ULN and <2x ULN
D. Minimal response, defined as decrease of ALT and AST serum levels, but still >2x ULN
E. Treatment failure, defined as no improvement or increase of ALT and AST serum levels
F. Changes in MELD score (and its components bilirubin, INR, creatinine) and in albumin and pseudocholinesterase
G. N-terminal procollagen-III-peptide, ELF score
H. Changes in quality of life measured with SF-36
I. Assessment of safety and tolerability of MMF versus AZA in patients with AIH
J. The level of ALAT, ASAT, GGT in both groups
K. Steroid and other side-effects scores consisting of VAS scores (0 – 10) by the physician for Cushing-face, buffalo hump, acne, striae, bruising and hirsutism.
L. Percentage of patients with biochemical remission
M. Ratio of ALAT to lowest ALAT ever

Secondary Outcome(s)

Secondary end point(s): A. Biochemical remission at 24 weeks and at anytime
B. Time to biochemical remission
C. Partial remission, defined as ALT and AST serum levels >1x ULN and <2x ULN
D. Minimal response, defined as decrease of ALT and AST serum levels but still >2x ULN
E. Treatment failure, defined as no improvement or increase of ALT and AST serum levels
F. Changes in MELD score (and its components bilirubin, INR, creatinine) and in albumin and pseudocholinesterase
G. N-terminal procollagen-III-peptide, ELF score
H. Changes in quality of life measured with SF-36
I. Assessment of safety of MMF versus AZA in patients with AIH
J. The level of ALT, AST, GGT in both groups
K. Steroid and other side-effects scores consisting of VAS scores (0 – 10) by the physician for Cushing-face, buffalo hump, acne, striae, bruising and hirsutism.
L. Percentage of patients with biochemical remission
M. Ratio of ALAT to lowest ALAT ever
N. Mood alterations, headache, insomnia
O. Diabetes (requiring medication)
P. Hypertension (requiring medication)
Q. Bone fractures, osteoporosis and muscular weakness
R. Glaucoma and increased intraocular pressure
S. Number of infections
T. Extrahepatic AIH manifestations (e.g. arthralgia)
U. Patient survival
V. Fatigue index
W. Pruritis VAS score

Timepoint(s) of evaluation of this end point: Patients will be seen at screening, baseline, 8 weeks, 12 weeks, 16 weeks, 20 weeks and 24 weeks.

Secondary ID(s)

NL57115

Source(s) of Monetary Support

Leiden university medical centre