Mycophenolate in Limited Cutaneous Systemic Sclerosis (MINIMISE-Pilot)

NCT04927390 | Unknown Phase 2 DMC

• 2 other identifiers: CTU/2017/3062019-004139-21
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 12

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.

Conditions

Systemic Sclerosis; Limited Cutaneous Systemic Sclerosis

Keywords

Limited Cutaneous Systemic Sclerosis; Mycophenolate Mofetil

Outcome Measures

Primary Outcomes (10)

• 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

  From first site activation up to a period of 12 months

• 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

  From first site activation up to a period of 12 months

• 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

  From first site activation up to a period of 12 months

• 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.

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

• 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.

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

• 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.

  From Screening, through study completion up to 36 months

• 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

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

• 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 .

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

• 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.

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

• 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

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

Secondary Outcomes (7)

• 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

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

• Number of reported deaths Baseline

  From Baseline , through study completion, up to 36 months

• 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

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

• 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

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

• 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.

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

Other Outcomes (2)

• Subgroup analyses of antinuclear antibody, ACA+ versus ACA-

  over 36 months

• IcSSc disease duration at baseline

  Baseline

Study Arms (2)

Mycophenolate Mofetil (MMF) Arm

EXPERIMENTAL

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.

Drug: Mycophenolate Mofetil 500mg

Control Arm

NO INTERVENTION

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

Interventions

Mycophenolate Mofetil 500mg DRUG

Mycophenolate Mofetil oral tablet twice daily for up to 96 weeks

Mycophenolate Mofetil (MMF) Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 -

You may not qualify if:

• 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:

Sponsors & Collaborators

• University College, London: lead
• Versus Arthritis: collaborator

Study Sites (12)

Royal United Hospitals Bath Nhs Foundation Trust

Bath, BA1 3NG, United Kingdom

Location

Southmead Hospital - NORTH BRISTOL NHS TRUST

Bristol, BS10 5NB, United Kingdom

Location

Darlington Memorial Hospital - County Durham and Darlington NHS Foundation Trust

Darlington, DL3 6HX, United Kingdom

Location

Ninewells Hospital - NHS Tayside

Dundee, DD1 9SY, United Kingdom

Location

Chapel Allerton Hospital - LEEDS TEACHING HOSPITALS NHS TRUST

Leeds, LS9 7TF, United Kingdom

Location

Aintree University Hospital NHS Foundation Trust

Liverpool, L9 7AL, United Kingdom

Location

Royal Free Hospital - Royal Free NHS Foundation Trust

London, NW3 2QG, United Kingdom

Location

Manchester Royal Infirmary - Manchester University NHS Foundation Trust

Manchester, M13 9WL, United Kingdom

Location

Salford Hospital - Northern Care Alliance NHS Foundation Trust

Manchester, M6 8HD, United Kingdom

Location

Freeman Hospital - THE NEWCASTLE UPON TYNE HOSPITALS NHS FOUNDATION TRUST

Newcastle, NE7 7DN, United Kingdom

Location

Royal Hallamshire Hospital - SHEFFIELD TEACHING HOSPITALS NHS FOUNDATION TRUST

Sheffield, S5 7AU, United Kingdom

Location

The Royal Wolverhampton Nhs Trust

Wolverhampton, WV10 0QP, United Kingdom

Location

Related Links

• Sponsor website link to trial

MeSH Terms

Conditions

Scleroderma, Systemic; Scleroderma, Limited

Interventions

Mycophenolic Acid

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases

Intervention Hierarchy (Ancestors)

Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids

Study Officials

• Christopher Denton

  University College, London

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

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

Study Record Dates

• First Submitted: May 19, 2021
• First Posted: June 16, 2021
• Study Start: December 8, 2021
• Primary Completion: November 30, 2023
• Study Completion: April 30, 2024
• Last Updated: July 27, 2023

Record last verified: 2023-07

Locations

GB (12)