This Study is Assessing the Safety and Efficacy of Immune Inhibition as a Treatment to Prevent Primary Graft Dysfunction

NCT06853223 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 25-43392
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

Lung transplant recipient survival lags other solid organ recipients, with the main early cause of death being primary graft dysfunction (PGD). PGD occurs in up to 1/3 of all recipients, is driven by the body's innate immune response, and has no known medical therapies for treatment or prevention. Investigators have recently shown that Natural Killer (NK) cells, a key innate immune cell, are critical in causing PGD. Importantly, the investigators found that Maraviroc, an FDA-approved drug that works to inhibit these immune cells, prevented lung injury in mouse models of PGD. The goal of this clinical trial is to learn if Maraviroc works to treat PGD in Lung Transplant patients who are above the age of 18 and have a PGD risk score greater than 50%. The objectives the study hopes to address are: To address the safety and tolerability of Maraviroc. To test a strategy for PGD enrichment in a lung transplant population. To measure the efficacy and biological efficacy of using Maraviroc. To study the biochemical, physiologic, and molecular effects of the drug on the body. This will be a double blind study where patients will either get the Maraviroc drug or a placebo. Researchers will then compare the two groups to address the above objectives. Participants will: Take drug Maraviroc or a placebo every 12 hours for 3 days post surgery. Follow up will occur during the entire length of stay at UCSF, about 16 days, with a single 12 month follow up once released.

Conditions

Lung Transplantation; Primary Graft Dysfunction; Acute Lung Injury(ALI); Natural Killer Cell Mediated Immunity

Outcome Measures

Primary Outcomes (1)

• Incidence of severe Primary Graft Dysfunction

  3 days

Secondary Outcomes (14)

• Post-operative outcomes associated with PGD

  3 months

• Other measures of Primary Graft Dysfunction

  3 days

• Biologic markers of efficacy.

  12 months

• Mortality within first year

  12 months

• Measures of allograft function

  12 months

Other Outcomes (1)

• Maraviroc PK evaluations

  4 days

Study Arms (2)

Maraviroc

EXPERIMENTAL

This arm is the Maraviroc drug which will be administered to patients.

Drug: Maraviroc

Placebo

PLACEBO COMPARATOR

This arm is the placebo drug which will be matched in appearance and taste to the Maraviroc and is available in PO and liquid (PFT) formulations.

Drug: Placebo

Interventions

Maraviroc DRUG

Product will be administered for 300 mg immediately preceding the lung transplant surgery and then will be administered every 12 hours. There will be 7 total doses. The first 3 will be 300 mg doses and the remaining 4 will be 150 mg doses. Maraviroc will be given oral (PO) or by feeding tube (PFT) in crushed format depending on the route availability.

Maraviroc

Placebo DRUG

Placebo in 300 and 150 mg formulations Product will be administered every 12 hours for 3 days. The placebo will be matched in appearance and taste to the Maraviroc and is available in PO and liquid (PFT) formulations.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Recipient scheduled to receive alternate induction regimen that is cell depleting such as anti-thymocyte globulin or alemtuzumab.
• Active chronic pulmonary infection in the recipient that are considered relative contraindications to lung transplantation such as Burkholderia or Mycobacterium abscessus.
• Recipient listed for concurrent heart or other solid organ transplantation.
• 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.

Sponsors & Collaborators

• University of California, San Francisco: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94143, United States

RECRUITING

MeSH Terms

Conditions

Primary Graft Dysfunction; Acute Lung Injury

Interventions

Maraviroc

Condition Hierarchy (Ancestors)

Reperfusion Injury; Vascular Diseases; Cardiovascular Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lung Injury; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Daniel Calabrese, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Daniel R Calabrese, MD

CONTACT

415-467-8700; Daniel.Calabrese@ucsf.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a randomized, double-blind, placebo-controlled phase 2 study.

Study Record Dates

• First Submitted: February 14, 2025
• First Posted: February 28, 2025
• Study Start: December 7, 2025
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): August 14, 2028
• Last Updated: January 20, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)