Maraviroc for Primary Graft Dysfunction

(MARAVIROC Trial)

Overseen By Daniel R Calabrese, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of California, San Francisco

Must be taking: Tacrolimus, Mycophenolate, Prednisone

Must not be taking: Cell depleting drugs

Disqualifiers: Chronic pulmonary infection, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

Duration: 3 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests Maraviroc to determine its effectiveness in treating primary graft dysfunction (PGD) in lung transplant recipients. PGD occurs when the new lung functions poorly due to the body's immune response. Researchers aim to discover if Maraviroc can safely reduce this immune reaction and prevent lung damage. Participants must be over 18, have undergone a double lung transplant, and be at high risk for PGD. The study involves taking Maraviroc or a placebo for three days post-surgery, with follow-ups during the hospital stay and a final check-up after a year. As a Phase 2 trial, this research measures Maraviroc's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant medical advancements.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications. However, it mentions that participants will be on a routine maintenance immunosuppression regimen including tacrolimus, mycophenolate, and prednisone.

Is there any evidence suggesting that Maraviroc is likely to be safe for humans?

Research has shown that Maraviroc has been studied for its safety in people, particularly for treating HIV. One long-term study examined its safety over more than five years in patients with HIV-1 and found it to be generally well-tolerated. Common side effects included mild to moderate issues like diarrhea, nausea, and tiredness, while serious reactions were rare.

Although Maraviroc has been used successfully in these other medical situations, this trial tests it for a different condition—primary graft dysfunction after lung transplants. Even though past results are promising, the trial aims to ensure it is just as safe and effective for this new use. Participants in this trial will help gather important information on its safety for this specific purpose. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for PGD?

Unlike the standard of care for primary graft dysfunction, which often involves supportive therapies and immunosuppressants, Maraviroc offers a novel approach by targeting the CCR5 receptor, a key player in immune response and inflammation. This unique mechanism of action could potentially reduce the severity of graft dysfunction by directly moderating the immune system's activity. Researchers are excited about Maraviroc because it not only represents a shift from current treatments focused on symptom management but also promises to address the underlying immune processes, offering hope for more effective and targeted interventions.

What evidence suggests that Maraviroc might be an effective treatment for primary graft dysfunction?

Research suggests that Maraviroc, which participants in this trial may receive, might help treat primary graft dysfunction (PGD) after lung transplants. In animal studies, Maraviroc prevented lung damage by blocking certain immune cells called Natural Killer (NK) cells, which can harm the new lung. The FDA has already approved this drug for other uses, indicating it can safely block these immune cells. Although human data on Maraviroc for PGD is limited, positive results in mice suggest it could reduce lung damage after transplants. More studies are needed to confirm these findings in humans. ^{1 2 6 7 8}

Who Is on the Research Team?

Daniel Calabrese, MD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

This trial is for lung transplant patients over 18 with a high risk of primary graft dysfunction (PGD). They must have a PGD risk score above 50%. The study excludes certain individuals, but specific exclusion criteria are not provided.

Inclusion Criteria

I am 18 years or older and on the lung transplant waitlist.

My risk of lung transplant rejection is over 50%.

Written informed consent obtained from subject or subject's legal representative and ability for subject to comply with the requirements of the study

Exclusion Criteria

I am scheduled for a treatment that reduces my immune cells.

I am receiving an organ from a donor with HIV, HCV, or HBV.

Recipient listed for concurrent heart or other solid organ transplantation

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive Maraviroc or placebo every 12 hours for 3 days post-surgery

3 days

Daily monitoring during hospital stay

Follow-up

Participants are monitored for safety and effectiveness after treatment during their hospital stay and have a single follow-up visit 12 months post-discharge

16 days in-hospital, 12 months post-discharge

In-hospital monitoring, 1 follow-up visit (in-person)

Long-term Follow-up

Participants are monitored for mortality and other long-term outcomes

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Maraviroc

Trial Overview The trial tests Maraviroc, an FDA-approved drug that may prevent lung injury after a transplant. It's compared to a placebo in a double-blind setup where neither doctors nor patients know who gets the real drug. Participants take their assigned treatment every 12 hours for three days post-surgery.

How Is the Trial Designed?

Group I: Maraviroc Experimental Treatment 1 Intervention

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

Group II: Placebo Placebo Group 1 Intervention

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.

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06853223

NCT06853223 | This Study is Assessing the Safety and ... This Study is Assessing the Safety and Efficacy of Immune Inhibition as a Treatment to Prevent Primary Graft Dysfunction (MARAVIROC).

2. withpower.com withpower.com/trial/phase-2-acute-lung-injury-5-2025-d726d

Maraviroc for Primary Graft Dysfunction · Info for Participants This trial is for lung transplant patients over 18 with a high risk of primary graft dysfunction (PGD). They must have a PGD risk score above 50%. The study ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6445759/

Extended CCR5 Blockade for Graft-Versus-Host Disease ... This study also confirms the safety profile of maraviroc, which in both studies was not associated with graft failure, an increase in infectious complications ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1684118225001422

Maraviroc treatment for hospitalized participants with non- ... The primary endpoints were the safety and efficacy of maraviroc ... dysfunction, and coagulation markers. Scand J Infect Dis, 46 (2014) ...

5. frontiersin.org frontiersin.org/journals/physiology/articles/10.3389/fphys.2025.1557182/full

Biomarkers for primary graft dysfunction after lung ... Lung transplantation remains an effective treatment for end-stage lung diseases, although its success is often limited by primary graft dysfunction (PGD) (Shah ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10721259/

CCR5 drives NK cell–associated airway damage in ... Primary graft dysfunction (PGD) limits clinical benefit after lung transplantation, a life-prolonging therapy for patients with end-stage disease.

7. astctjournal.org astctjournal.org/article/S1083-8791(15)01154-4/pdf

Phase 1 Study of Maraviroc As Acute Graft- ... Background: Sickle Cell Disease can be cured with allogeneic stem cell transplant, but excellent outcomes have been limited to transplants using HLA matched ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3893710/

Five-Year Safety Evaluation of Maraviroc in HIV-1–Infected ... In this study, we report the pooled safety findings from the MOTIVATE 1 and MOTIVATE 2 phase 3 studies for >5 years, the longest-term safety data available with ...