CCR5 immune blockade to prevent primary graft dysfunction after lung transplant

A Randomized Trial of CCR5 Inhibition as a Complement to Lung Transplant Induction Immunosuppression

This trial will test whether the drug Maraviroc can prevent primary graft dysfunction in adults undergoing bilateral lung transplantation who have a PGD risk score greater than 50%.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 120 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of California, San Francisco (Academic / other)
• Drugs / interventions: basiliximab, alemtuzumab, prednisone
• Locations: 1 site (San Francisco, California)
• Trial ID: NCT06853223 on ClinicalTrials.gov

What this trial studies

This randomized Phase 2 interventional trial gives adults at high risk for PGD either Maraviroc or placebo around the time of bilateral lung transplantation to test safety, tolerability, and biological effect. Investigators will measure clinical outcomes including PGD incidence, monitor adverse events and drug-drug interactions, and measure Maraviroc levels in plasma and bronchoalveolar lavage. They will assess bronchoalveolar lavage NK cells and other donor and recipient biomarkers as surrogate markers of biological efficacy and to develop subphenotyping assays for future multicenter trials. A secondary aim is to pilot an enrichment strategy to identify and recruit patients with a greater than 50% predicted PGD risk ahead of transplant.

Who should consider this trial

Good fit: Adults aged 18 or older listed for bilateral lung transplantation with a calculated PGD risk score above 50% who can give informed consent and receive the planned induction and maintenance immunosuppression are ideal candidates.

Not a fit: Patients who require cell‑depleting induction regimens, have active chronic pulmonary infections considered contraindications to transplant, or receive certain infected donor organs are excluded and unlikely to benefit from this intervention.

Why it matters

Potential benefit: If successful, Maraviroc could reduce rates of early primary graft dysfunction and related complications after lung transplantation.

How similar studies have performed: Preclinical mouse studies showed that Maraviroc prevented lung injury from PGD, but clinical use of CCR5 inhibition for PGD in humans is novel with limited prior clinical data.

Eligibility criteria

Inclusion Criteria:

1. Male or female ≥18 years of age at the time of lung transplant waitlisting.
2. Listed for a bilateral lung transplantation.
3. Written informed consent obtained from subject or subject's legal representative and ability for subject to comply with the requirements of the study.
4. PGD risk score \> 50% at the time of donor organ offer
5. Planned induction with basiliximab, mycophenolatge, and prednisone and routine maintenance immunosuppression of tacrolimus, mycophenolate and prednisone.

Exclusion Criteria:

1. Recipient scheduled to receive alternate induction regimen that is cell depleting such as anti-thymocyte globulin or alemtuzumab.
2. Active chronic pulmonary infection in the recipient that are considered relative contraindications to lung transplantation such as Burkholderia or Mycobacterium abscessus.
3. Recipients receiving HIV, HCV or HBV positive donor organs. Only documented infections are considered exclusion criteria. Recipients receiving increased risk organs will not be excluded.
4. Recipient listed for concurrent heart or other solid organ transplantation.
5. Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data.

Where this trial is running

San Francisco, California

• University of California, San Francisco — San Francisco, California, United States (Recruiting)

Study contacts

• Principal investigator: Daniel Calabrese, MD — University of California, San Francisco
• Study coordinator: Daniel R Calabrese, MD

Conditions Primary Graft Dysfunction; Lung Transplantation; Acute Lung Injury; Natural Killer Cell Mediated Immunity