Back to results

Mycophenolate in Limited Cutaneous Systemic Sclerosis (MINIMISE-Pilot) (MINIMISE)

Primary Purpose

Systemic Sclerosis, Limited Cutaneous Systemic Sclerosis

Status

Active

Phase

Phase 2

Locations

United Kingdom

Study Type

Interventional

Intervention

Mycophenolate Mofetil 500mg

About this trial

This is an interventional treatment trial for Systemic Sclerosis focused on measuring Limited Cutaneous Systemic Sclerosis, Mycophenolate Mofetil

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Participants with lcSSc classified by the 2013 EULAR ACR criteria for limited cutaneous subset of SSc
Participants with less than 7 years disease duration from first non-Raynaud's manifestation of SSc
Participants aged 18 years or more (≥ 18 years) at screening visit
If women of child bearing potential, the participant must have a negative pregnancy test at screening and baseline visits
Negative viral screen for HIV, Hepatitis B and C
Ability to provide full informed consent
Registered with a GP practice in the UK
Participants must be willing to attend for follow up visits (at site or remotely) and to comply with study-related procedures -

Exclusion Criteria:

Having already developed a complication of SSc that requires initiation of MMF or an alternative major immunosuppressive drug for SSc such as methotrexate, cyclophosphamide or azathioprine
Treatment with methotrexate, cyclosporine A, azathioprine, mycophenolate mofetil (MMF), rapamycin, colchicine, D-penicillamine, within ≤ 4 weeks prior to the baseline visit date
Contraindication to MMF (e.g. active infection that would preclude MMF in judgement of investigator), or previous intolerance of MMF
Any clinical condition which the investigator considers would make the patient unsuitable for the trial
Pregnancy (or planned pregnancy during trial participation) and/or breastfeeding
Women of child bearing potential and male participants with a partner of child bearing potential not willing to use adequate contraception as described in section 6.3.1.4 for the duration of trial treatment and within the time points specified following last trial treatment.
Active chronic infection such as COVID-19, tuberculosis, pneumocystis, cytomegalovirus, herpes simplex virus, herpes zoster and atypical mycobacteria.
Suitability for enrolment once the participant has recovered from infection will be based on Investigator judgment.
Infection history:
i. Hospitalisation for treatment of infection within ≤ 8 weeks of screening visit date
ii. Use of parenteral (IV or IM) antibiotics (antibacterials, antivirals, anti-fungals, or anti-parasitic agents) within ≤ 4 weeks of screening visit date
Receipt of a live-attenuated vaccine within ≤ 12 weeks of screening visit date
Participants enrolled in any other interventional trial within ≤ 4 weeks of the screening visit date (co-enrolment in observational studies is acceptable)
Current drug or alcohol abuse or dependence, or a history of drug or alcohol abuse or dependence within ≤ 52 weeks prior to screening visit date.
Any of the following laboratory results at screening visit:
- Glomerular filtration rate (GFR) <60 ml/min/1.73m²
- Absolute neutrophil count (ANC) < 1.6 x 10^9/l
- ALT or AST > 2 x ULN
Participants not willing or unable to attend on-site screening visit.

Sites / Locations

Royal United Hospitals Bath Nhs Foundation Trust
Southmead Hospital - NORTH BRISTOL NHS TRUST
Darlington Memorial Hospital - County Durham and Darlington NHS Foundation Trust
Ninewells Hospital - NHS Tayside
Chapel Allerton Hospital - LEEDS TEACHING HOSPITALS NHS TRUST
Aintree University Hospital NHS Foundation Trust
Royal Free Hospital - Royal Free NHS Foundation Trust
Manchester Royal Infirmary - Manchester University NHS Foundation Trust
Salford Hospital - Northern Care Alliance NHS Foundation Trust
Freeman Hospital - THE NEWCASTLE UPON TYNE HOSPITALS NHS FOUNDATION TRUST
Royal Hallamshire Hospital - SHEFFIELD TEACHING HOSPITALS NHS FOUNDATION TRUST
The Royal Wolverhampton Nhs Trust

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Mycophenolate Mofetil (MMF) Arm

Control Arm

Arm Description

Participants will receive mycophenolate mofetil (MMF) for up to 96 weeks, in addition to their background Standard of Care medication for systemic sclerosis related symptoms. They will receive 500mg twice daily over the first 4 weeks following their randomisation, and if tolerated the dose will be increased to a target dose of 1g twice daily starting from week 5 until their Final visit.

Standard of Care (no immunosuppression) for systemic sclerosis related symptoms.

Outcomes

Primary Outcome Measures

The total number of lcSSc patients screened during the 12 month recruitment period, measured from information provided on the site Screening Logs

The total number of lcSSc patients screened will be captured on detailed screening logs

The proportion of participants who provide consent during the 12 month recruitment period, measured from information provided on the site Screening Logs

Participant informed consent will be captured in detailed screening logs

The proportion of participants who meet the eligibility criteria during the 12 month recruitment period, measured from information provided on the site Screening Logs

Information on participants who meet the eligibility criteria will be captured on detailed screening logs

Adherence to trial treatment by participants randomised to the MMF arm as assessed by the Participant Dosing Diaries.

Participant self-reported adherence using participant dosing diaries to be completed daily. Diaries will be provided to all participants randomised to MMF to record their daily trial medication intake, in addition to any dose modifications and dose interruptions for the duration of their time in the study.

Drug adherence rate from participants randomised to the MMF arm, measured by Pharmacy Accountability Logs

Pharmacy dispensing accountability logs will record the number of pills dispensed at each visit and the number of pills returned by the participant.(i.e. pill count) The number of pills taken is calculated by subtracting the count of the number of pills remaining from the total number of pills dispensed. The drug adherence rate is then calculated by dividing the number of pills taken by number of days elapsed since the last dispense.

Adherence to the study protocol by participating sites as assessed by the number of protocol deviations reported using the Protocol Deviation Reports

Sites to report deviations and sponsor protocol compliance reviews during central, remote and on-site monitoring to be reported in Protocol Deviation Reports.

The proportion of participants intolerant to MMF who discontinue trial treatment from Baseline for a minimum of 48 weeks or a maximum of 96 weeks as assessed by the Participant withdrawal Logs

The number of participants who withdraw from trial treatment ONLY will be recorded using detailed Participant Withdrawal Logs

The total number of participants randomised to MMF who reach the target dose of 2g a day, measured by medication intake information captured in the Participant Dosing Diaries

Self-reported: Participant Dosing Diaries will be provided to all participants randomised to MMF to record dose escalation information and daily intake of the IMP .

The total number of participants randomised to MMF and Control who reach a clinical worsening of disease progression, measured by the modified Rodnan Skin Score (mRSS) from Baseline, every 6 months until Final trial visit.

Validated physical examination method for estimating skin induration. It is scored on a 0 (normal) to 3+ (severe induration) ordinal scales over 17 body areas, with a maximum score of 51 and is used to categorise severity of SSc. Minimally clinically significant difference in mRSS is 3-5 points. The measurement of time to clinically important disease progression will demonstrate a clinically important advantage of active treatment compared with no immunosuppression if a beneficial effect is found.

The number of participant loss to follow- up as assessed by the Participant Withdrawal Logs

The number of participant loss to follow -up in each group (MMF or control) will be recorded using detailed Participant Withdrawal Logs

Secondary Outcome Measures

Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 from Baseline for a minimum of 48 weeks or a maximum of 96 weeks

Number of reported deaths Baseline

Participants self report, review of hospital records

Changes in functional ability from Baseline for a minimum of 48 weeks or a maximum of 96 weeks as measured by the Scleroderma Assessment Questionnaire

The Scleroderma Assessment Questionnaire is a self-assessed measure ranging from 0-3 (where 0 = without difficulty and 3 = unable to do) for several questions including vascular, respiratory, gastrointestinal, musculoskeletal, and overall disease status with 23 questions divided into 4 groups.

Quality of Life as measured by the EQ5-5D-5L Questionnaire from Baseline for a minimum of 48 weeks or a maximum of 96 weeks

EQ-5D- 5L is a participant self -reported questionnaire which evaluates the generic quality of life at the time of completion. It comprises of one question for each of the five dimensions that include mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Respondents are asked to choose the statement in each dimension that best describes their health status. Their responses are coded as a number (1, 2, or 3) that corresponds to the respective level of severity: 1 indicates no problems, 2 some problems, and 3 extreme problems

Changes in pain and disability from Baseline for a minimum of 48 weeks or a maximum of 96 weeks as measured by the Patient Global Questionnaire.

Self-reported questionnaire assessed by a single question to reflect the participants perspective on their health overall. Rating scale used with a 0-100 response, where 0= has no effect at all, 100= worst possible effect.

Changes in pain and disability from Baseline for a minimum of 48 weeks or a maximum of 96 weeks as measured by the Physician's Global Questionnaire.

Physician-reported questionnaire assessed by a single question to reflect the participants perspective on their health overall. Rating scale used with a 0-100 response, where 0= has no effect at all, 100= worst possible effect.

Scleroderma skin activity and skin-related health related quality of life from Baseline for a minimum of 48 weeks or a maximum of 96 weeks as measured by PASTUL-SSPRO score

Self-reported questionnaire specifies a grading of skin (normal (0), mild (1), moderate (2), severely (3) thickened) at eight sites corresponding to mRSS with maximum score assigned to each site (PASTUL), and that assesses health-related quality of life (HRQOL) related to skin involvement in SSc. It has 18 items representing 4 HRQOL scales: physical effects, emotional effects, physical function, and social effects. All items are scored from 0 (better) to 6 (worse) (SSPRO).

Full Information

NCT ID

NCT04927390

First Posted

May 19, 2021

Last Updated

July 26, 2023

Sponsor

University College, London

Collaborators

Versus Arthritis

1. Study Identification

Unique Protocol Identification Number

NCT04927390

Brief Title

Mycophenolate in Limited Cutaneous Systemic Sclerosis (MINIMISE-Pilot)

Acronym

MINIMISE

Official Title

A Randomised Prospective Open Label Pilot Trial Comparing Mycophenolate Mofetil (MMF) With no Immunosuppression in Adults With Limited Cutaneous Systemic Sclerosis

Study Type

Interventional

2. Study Status

Record Verification Date

July 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

December 8, 2021 (Actual)

Primary Completion Date

November 30, 2023 (Anticipated)

Study Completion Date

April 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University College, London

Collaborators

Versus Arthritis

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Systemic sclerosis or scleroderma is an autoimmune condition that cause thickening and hardening of the skin, but can also affect internal organs. There are two major subsets of scleroderma: the limited cutaneous systemic sclerosis (lcSSc) that usually affects the skin of the face, neck, lower legs or lower arms, but can also lead to internal organ complications, and the diffuse cutaneous systemic sclerosis (dcSSc) that may affect blood circulation and internal organs, as well as the skin. To date there is no drug that has been definitively proven to cure or modify the course of scleroderma. However, there is emerging evidence that immunosuppression and specifically mycophenolate mofetil (MMF) may be beneficial in lcSSc. The MINIMISE-Pilot trial would be an important first step to evaluate the risk and potential benefit to this disease group. MMF as the intervention of choice is both appropriate and timely, as it has been routinely used in the management of dcSSc. The aim of this pilot trial is to explore whether the immunosuppressive agent MMF can slow down disease progression in patients with lcSSc compared to the current standard of care alone. This pilot trial will also provide critical information for the development of a future large trial that could potentially transform lcSSc patient management.

Detailed Description

The MINIMISE-Pilot trial aims to explore whether the immunosuppressive agent mycophenolate mofetil (MMF) at a target dose of 2g daily can slow down disease progression in patients with limited cutaneous systemic sclerosis (lcSSc) compared to the current standard of care alone. This pilot trial will also provide critical information for the development of a future large trial that could potentially transform lcSSc patient management. This is an open label randomised prospective trial that will recruit 120 participants aged 18 and older with limited cutaneous systemic sclerosis across 13 sites in the UK. Following a screening visit, eligible participants will attend a baseline visit where they will be randomly allocated into one of two groups; MMF or Control. Those in the first group are given mycophenolate mofetil (MMF) taken daily by mouth for up to 96 weeks, in addition to their background Standard of Care medication for SSc related symptoms. Those in the second group will not receive any MMF but will remain on their standard of care medication alone. Participants are expected to be followed up for a minimum of 48 weeks or a maximum of 96 weeks. The trial will involve five (5) clinic visits which are expected to be carried out at the same time of the participants' normal hospital appointment with their scleroderma specialist. Participants from both groups will have the same assessments. Participants are expected to return to the clinics at Week 24, 48, 72 and 96. However, participants allocated to the MMF group will have additional blood samples taken for safety monitoring every 2 weeks for the first 8 weeks, then every 4 weeks for the following 12 weeks. Thereafter, every 12 weeks up to their final visit. All the participants will receive four (4) routine telephone calls in between their clinic visits.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Systemic Sclerosis, Limited Cutaneous Systemic Sclerosis

Keywords

Limited Cutaneous Systemic Sclerosis, Mycophenolate Mofetil

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Model Description

Eligible participants will be randomised 1:1 to receive Mycophenolate Mofetil plus Standard of Care (MMF Group) or Standard of Care alone (Control Group).

Masking

None (Open Label)

Allocation

Randomized

Enrollment

120 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Mycophenolate Mofetil (MMF) Arm

Arm Type

Experimental

Arm Description

Arm Title

Control Arm

Arm Type

No Intervention

Arm Description

Standard of Care (no immunosuppression) for systemic sclerosis related symptoms.

Intervention Type

Drug

Intervention Name(s)

Mycophenolate Mofetil 500mg

Intervention Description

Mycophenolate Mofetil oral tablet twice daily for up to 96 weeks

Primary Outcome Measure Information:

Title

The total number of lcSSc patients screened during the 12 month recruitment period, measured from information provided on the site Screening Logs

Description

The total number of lcSSc patients screened will be captured on detailed screening logs

Time Frame

From first site activation up to a period of 12 months

Title

The proportion of participants who provide consent during the 12 month recruitment period, measured from information provided on the site Screening Logs

Description

Participant informed consent will be captured in detailed screening logs

Time Frame

From first site activation up to a period of 12 months

Title

The proportion of participants who meet the eligibility criteria during the 12 month recruitment period, measured from information provided on the site Screening Logs

Description

Information on participants who meet the eligibility criteria will be captured on detailed screening logs

Time Frame

From first site activation up to a period of 12 months

Title

Adherence to trial treatment by participants randomised to the MMF arm as assessed by the Participant Dosing Diaries.

Description

Time Frame

From Baseline, up until a minimum of 48 weeks or a maximum of 96 weeks

Title

Drug adherence rate from participants randomised to the MMF arm, measured by Pharmacy Accountability Logs

Description

Time Frame

From first participant dispensing, through study completion up to 36 months

Title

Adherence to the study protocol by participating sites as assessed by the number of protocol deviations reported using the Protocol Deviation Reports

Description

Sites to report deviations and sponsor protocol compliance reviews during central, remote and on-site monitoring to be reported in Protocol Deviation Reports.

Time Frame

From Screening, through study completion up to 36 months

Title

The proportion of participants intolerant to MMF who discontinue trial treatment from Baseline for a minimum of 48 weeks or a maximum of 96 weeks as assessed by the Participant withdrawal Logs

Description

The number of participants who withdraw from trial treatment ONLY will be recorded using detailed Participant Withdrawal Logs

Time Frame

From Baseline, up until a minimum of 48 weeks or a maximum of 96 weeks

Title

The total number of participants randomised to MMF who reach the target dose of 2g a day, measured by medication intake information captured in the Participant Dosing Diaries

Description

Self-reported: Participant Dosing Diaries will be provided to all participants randomised to MMF to record dose escalation information and daily intake of the IMP .

Time Frame

From Baseline through to study completion for a minimum of 48 weeks or a maximum of 96 weeks

Title

Description

Time Frame

From Baseline, every 6 months, through study completion up until a minimum of 48 weeks or a maximum of 96 weeks

Title

The number of participant loss to follow- up as assessed by the Participant Withdrawal Logs

Description

The number of participant loss to follow -up in each group (MMF or control) will be recorded using detailed Participant Withdrawal Logs

Time Frame

From Baseline, through study completion up until a minimum of 48 weeks or a maximum of 96 weeks

Secondary Outcome Measure Information:

Title

Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 from Baseline for a minimum of 48 weeks or a maximum of 96 weeks

Description

Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 from Baseline for a minimum of 48 weeks or a maximum of 96 weeks

Time Frame

From Baseline, through study completion for a minimum of 48 weeks or a maximum of 96 weeks

Title

Number of reported deaths Baseline

Description

Participants self report, review of hospital records

Time Frame

From Baseline , through study completion, up to 36 months

Title

Changes in functional ability from Baseline for a minimum of 48 weeks or a maximum of 96 weeks as measured by the Scleroderma Assessment Questionnaire

Description

Time Frame

From Baseline, every 6 months, through study completion up until a minimum of 48 weeks or a maximum of 96 weeks

Title

Quality of Life as measured by the EQ5-5D-5L Questionnaire from Baseline for a minimum of 48 weeks or a maximum of 96 weeks

Description

Time Frame

From Baseline, every 6 months, through study completion up until a minimum of 48 weeks or a maximum of 96 weeks

Title

Changes in pain and disability from Baseline for a minimum of 48 weeks or a maximum of 96 weeks as measured by the Patient Global Questionnaire.

Description

Time Frame

From Baseline, every 6 months, through study completion up until a minimum of 48 weeks or a maximum of 96 weeks

Title

Changes in pain and disability from Baseline for a minimum of 48 weeks or a maximum of 96 weeks as measured by the Physician's Global Questionnaire.

Description

Time Frame

From Baseline, every 6 months, through study completion up until a minimum of 48 weeks or a maximum of 96 weeks]

Title

Scleroderma skin activity and skin-related health related quality of life from Baseline for a minimum of 48 weeks or a maximum of 96 weeks as measured by PASTUL-SSPRO score

Description

Time Frame

From Baseline, every 6 months, through study completion up until a minimum of 48 weeks or a maximum of 96 weeks

Other Pre-specified Outcome Measures:

Title

Subgroup analyses of antinuclear antibody, ACA+ versus ACA-

Description

Standard diagnostic laboratory assays for antinuclear antibodies

Time Frame

over 36 months

Title

IcSSc disease duration at baseline

Description

IcSSc disease duration at baseline up to 4 years versus four years or more

Time Frame

Baseline

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Participants with lcSSc classified by the 2013 EULAR ACR criteria for limited cutaneous subset of SSc Participants with less than 7 years disease duration from first non-Raynaud's manifestation of SSc Participants aged 18 years or more (≥ 18 years) at screening visit If women of child bearing potential, the participant must have a negative pregnancy test at screening and baseline visits Negative viral screen for HIV, Hepatitis B and C Ability to provide full informed consent Registered with a GP practice in the UK Participants must be willing to attend for follow up visits (at site or remotely) and to comply with study-related procedures - Exclusion Criteria: Having already developed a complication of SSc that requires initiation of MMF or an alternative major immunosuppressive drug for SSc such as methotrexate, cyclophosphamide or azathioprine Treatment with methotrexate, cyclosporine A, azathioprine, mycophenolate mofetil (MMF), rapamycin, colchicine, D-penicillamine, within ≤ 4 weeks prior to the baseline visit date Contraindication to MMF (e.g. active infection that would preclude MMF in judgement of investigator), or previous intolerance of MMF Any clinical condition which the investigator considers would make the patient unsuitable for the trial Pregnancy (or planned pregnancy during trial participation) and/or breastfeeding Women of child bearing potential and male participants with a partner of child bearing potential not willing to use adequate contraception as described in section 6.3.1.4 for the duration of trial treatment and within the time points specified following last trial treatment. Active chronic infection such as COVID-19, tuberculosis, pneumocystis, cytomegalovirus, herpes simplex virus, herpes zoster and atypical mycobacteria. Suitability for enrolment once the participant has recovered from infection will be based on Investigator judgment. Infection history: i. Hospitalisation for treatment of infection within ≤ 8 weeks of screening visit date ii. Use of parenteral (IV or IM) antibiotics (antibacterials, antivirals, anti-fungals, or anti-parasitic agents) within ≤ 4 weeks of screening visit date Receipt of a live-attenuated vaccine within ≤ 12 weeks of screening visit date Participants enrolled in any other interventional trial within ≤ 4 weeks of the screening visit date (co-enrolment in observational studies is acceptable) Current drug or alcohol abuse or dependence, or a history of drug or alcohol abuse or dependence within ≤ 52 weeks prior to screening visit date. Any of the following laboratory results at screening visit: Glomerular filtration rate (GFR) <60 ml/min/1.73m² Absolute neutrophil count (ANC) < 1.6 x 10^9/l ALT or AST > 2 x ULN Participants not willing or unable to attend on-site screening visit.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Christopher Denton

Organizational Affiliation

University College, London

Official's Role

Principal Investigator

Facility Information:

Facility Name

Royal United Hospitals Bath Nhs Foundation Trust

City

Bath

ZIP/Postal Code

BA1 3NG

Country

United Kingdom

Facility Name

Southmead Hospital - NORTH BRISTOL NHS TRUST

City

Bristol

ZIP/Postal Code

BS10 5NB

Country

United Kingdom

Facility Name

Darlington Memorial Hospital - County Durham and Darlington NHS Foundation Trust

City

Darlington

ZIP/Postal Code

DL3 6HX

Country

United Kingdom

Facility Name

Ninewells Hospital - NHS Tayside

City

Dundee

ZIP/Postal Code

DD1 9SY

Country

United Kingdom

Facility Name

Chapel Allerton Hospital - LEEDS TEACHING HOSPITALS NHS TRUST

City

Leeds

ZIP/Postal Code

LS9 7TF

Country

United Kingdom

Facility Name

Aintree University Hospital NHS Foundation Trust

City

Liverpool

ZIP/Postal Code

L9 7AL

Country

United Kingdom

Facility Name

Royal Free Hospital - Royal Free NHS Foundation Trust

City

London

ZIP/Postal Code

NW3 2QG

Country

United Kingdom

Facility Name

Manchester Royal Infirmary - Manchester University NHS Foundation Trust

City

Manchester

ZIP/Postal Code

M13 9WL

Country

United Kingdom

Facility Name

Salford Hospital - Northern Care Alliance NHS Foundation Trust

City

Manchester

ZIP/Postal Code

M6 8HD

Country

United Kingdom

Facility Name

Freeman Hospital - THE NEWCASTLE UPON TYNE HOSPITALS NHS FOUNDATION TRUST

City

Newcastle

ZIP/Postal Code

NE7 7DN

Country

United Kingdom

Facility Name

Royal Hallamshire Hospital - SHEFFIELD TEACHING HOSPITALS NHS FOUNDATION TRUST

City

Sheffield

ZIP/Postal Code

S5 7AU

Country

United Kingdom

Facility Name

The Royal Wolverhampton Nhs Trust

City

Wolverhampton

ZIP/Postal Code

WV10 0QP

Country

United Kingdom

12. IPD Sharing Statement

Plan to Share IPD

Undecided

IPD Sharing Plan Description

No plan to share IPD has been made at this time

Links:

URL

https://www.ucl.ac.uk/comprehensive-clinical-trials-unit/research-projects/2020/may/minimise

Description

Sponsor website link to trial

Learn more about this trial

Mycophenolate in Limited Cutaneous Systemic Sclerosis (MINIMISE-Pilot)

We'll reach out to this number within 24 hrs