Trial of Bone-marrow Derived Mesenchymal Stromal Cells (MSC) for New Onset Chronic Lung Allograft Dysfunction

NCT02709343 | Completed Phase 2 DMC

• 1 other identifier: ASSIST-CLAD
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 5

Brief Summary

This study is designed for lung transplant patients who have developed chronic lung allograft dysfunction (CLAD). Consented patients will receive 4 intravenous doses of allogeneic, bone-marrow-derived MSCs (2\*10\^6 cells/kg/dose) or matching placebo over a period of 2 weeks with a 12 month follow up.

Conditions

Chronic Lung Allograft Dysfunction (CLAD)

Outcome Measures

Primary Outcomes (1)

• Progression-free survival

  Progression-free survival is a composite end-point of freedom from CLAD progression or death from any-cause. CLAD progression is defined as fall in FEV1 \> 10% from the baseline (screening visit) FEV1 to the 12 month (week 54) visit.

  From baseline to week 54

Secondary Outcomes (12)

• Time to fall in FEV1 > 10%

  From the baseline (screening) visit

• Freedom from Bronchiolitis Obliterans Syndrome (BOS) grade 3

  Week 54

• All cause mortality

  Week 54

• CLAD-specific mortality

  Week 54

• Freedom from acute rejection

  From baseline to week 54

Study Arms (2)

Bone-marrow derived MSCs

EXPERIMENTAL

4 doses of Allogeneic bone-marrow derived MSCs (2x106 cells/kg) given intravenously twice weekly for 2 weeks

Drug: Bone-marrow derived MSCs

Placebo

PLACEBO COMPARATOR

Placebo product manufactured to look like MSCs

Drug: Placebo

Interventions

Bone-marrow derived MSCs DRUG

Allogeneic ex vivo expanded, bone marrow-derived mesenchymal stromal cells

Also known as: MSC

Bone-marrow derived MSCs

Placebo DRUG

Placebo product visually very similar to mesenchymal stromal cells

Placebo

Eligibility Criteria

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

You may qualify if:

• Bilateral lung transplant recipients aged ≥ 18 years and at least 6 months post-transplant. Patients with other organs transplanted (eg heart, liver, kidney) or those who have undergone lobar transplantation, or re-transplantation, are potentially eligible.
• New-onset CLAD (defined as a persistent (3weeks apart) fall in FEV1 of at least 20% from the mean of the two best post-transplant values taken at least 3 weeks apart) in the 12 months prior to the screening visit. Other causes of a fall in FEV1 (acute cellular or humoral rejection, active infection, anastomotic stenosis etc.) must be excluded as per international guidelines.
• Stable immunosuppression regimen, as assessed by the investigator, in the 8 weeks prior to the screening visit.
• Available for all specified assessments at the study site through the completion of the study, including the protocol bronchoscopies.
• Provision of written informed consent.

You may not qualify if:

• Any condition that in the opinion of the Investigator may interfere with the safety of the patient, his / her completion of required follow-up visits or evaluation of the study objectives
• Untreated cellular or humoral rejection
• Clinically meaningful and untreated viral, bacterial or fungal infection
• Use of azithromycin or another macrolide antibiotic, if commenced within 8 weeks of the screening visit
• Intravenous pulsed methylprednisolone, within 4 weeks of the screening visit
• Use of extracorporeal photopheresis, within 4 weeks of the screening visit
• Use of total lymphoid irradiation, within 4 weeks of the screening visit
• Poor functional status not expected to survive 6 months
• Allergy to beef products
• Women who are pregnant, breast-feeding or unwilling to use adequate contraception
• Patients who are currently participating in another interventional clinical trial

Sponsors & Collaborators

• The University of Queensland: lead
• Isopogen: collaborator
• Cell and Tissue Therapies: collaborator

Study Sites (5)

St Vincents Hospital

Sydney, New South Wales, 2010, Australia

Location

The Prince Charles Hospital

Brisbane, Queensland, 4032, Australia

Location

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

The Alfred Hospital

Melbourne, Victoria, 3000, Australia

Location

Fiona Stanley Hospital

Murdoch, Western Australia, 6150, Australia

Location

Study Officials

• Daniel Chambers, MBBS MD

  University of Queensland & The Prince Charles Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: A/Prof Daniel Chambers

Study Record Dates

• First Submitted: March 1, 2016
• First Posted: March 16, 2016
• Study Start: April 21, 2017
• Primary Completion: September 13, 2023
• Study Completion: October 25, 2023
• Last Updated: December 6, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will share

Locations

AU (5)