Alvelestat for Bronchiolitis Obliterans Syndrome

Not currently recruiting at 1 trial location

Overseen By Najla El Jurdi, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: National Cancer Institute (NCI)

Must be taking: Inhaled steroids, Montelukast

Must not be taking: Neutrophil elastase inhibitors

Disqualifiers: Pregnancy, Significant alcohol use, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of a new drug, alvelestat (MPH966), for individuals with bronchiolitis obliterans syndrome (BOS), a lung condition that can occur after a stem cell transplant. Researchers aim to determine if alvelestat can improve lung function by reducing the activity of neutrophil elastase, which may contribute to BOS. The trial seeks adults who have undergone a stem cell transplant and now have BOS along with chronic graft versus host disease (cGVHD), which can cause breathing difficulties in daily life. Participants will take the drug in varying doses to identify the most effective one and monitor changes in their lung health over time. As a Phase 1, Phase 2 trial, this research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking advancements in BOS treatment.

Do I need to stop taking my current medications to join the trial?

The trial does not specify that you must stop taking all current medications, but if you are on azithromycin, you need to stop it at least 2 weeks before joining. If you are on systemic therapy for cGVHD, you must be on stable or tapering doses for the previous 4 weeks.

Is there any evidence suggesting that alvelestat (MPH966) is likely to be safe for humans?

Research shows that alvelestat (MPH966) is being tested for safety in people with bronchiolitis obliterans syndrome (BOS). Earlier studies found that alvelestat, a pill, may help with BOS symptoms by reducing the activity of a substance called neutrophil elastase.

These studies examined how well people handle the drug and what side effects it might cause. So far, results suggest that alvelestat is generally well-tolerated by patients. The main goal has been to find the best dose that works effectively while minimizing side effects.

In research involving other conditions, like alpha-1 antitrypsin deficiency (AATD), alvelestat was used safely, suggesting it might also be safe for BOS. However, more research is needed to fully understand its safety for BOS. Researchers closely monitored participants to manage any side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about Alvelestat for bronchiolitis obliterans syndrome because it offers a novel approach by targeting neutrophil elastase, an enzyme linked to lung damage. Current treatments like corticosteroids and immunosuppressants mainly aim to reduce inflammation and suppress the immune system, but they don't specifically address the enzyme activity contributing to the disease progression. Alvelestat's ability to directly inhibit neutrophil elastase represents a potential breakthrough by tackling the underlying cause of tissue damage, promising more effective management of the condition.

What evidence suggests that alvelestat might be an effective treatment for bronchiolitis obliterans syndrome?

Research has shown that alvelestat (MPH966), the investigational treatment in this trial, might help treat bronchiolitis obliterans syndrome (BOS) by blocking an enzyme called neutrophil elastase, which may be involved in this condition. Earlier studies found that alvelestat is generally safe and could help stabilize the disease in people with advanced BOS. Specifically, improvements appeared in certain biomarkers, indicating how the body responds to the treatment. While more research is needed, these early results suggest that alvelestat might improve lung function in people with BOS. ^{1 2 6 7 8}

Who Is on the Research Team?

Najla El Jurdi, M.D.

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

Adults over 18 who've had a stem cell transplant and suffer from chronic graft versus host disease (cGVHD) with Bronchiolitis Obliterans Syndrome (BOS). They must have been treated for cGVHD, have certain lung function test results, stable organ/marrow function, and agree to contraception. Excluded are those with recent malignancy treatments, uncontrolled illnesses, pregnancy/breastfeeding, prior neutrophil elastase inhibitors use or significant alcohol consumption.

Inclusion Criteria

I have chronic GVHD and BOS after my stem cell transplant.

I have been on a specific treatment for at least 3 months before joining.

I was diagnosed with BOS within the last 5 years for Phase 2, or any time for Phase 1b.

Exclusion Criteria

I have non-alcoholic fatty liver disease or have been on related medication for over 2 weeks in the last year.

I have not had any serious illnesses in the last month.

I have used neutrophil elastase inhibitors before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Phase 1b Treatment

Participants receive escalating doses of alvelestat (MPH966) to determine the optimal biologic dose and safety over 8 weeks

8 weeks

Weekly visits for dose escalation

Phase 2 Treatment

Participants receive alvelestat (MPH966) at the optimal biologic dose for up to 6 months to assess efficacy

6 months

Monthly visits for efficacy assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Periodic contact for follow-up

Optional Continuation

Participants with stable or responding disease may continue therapy for an additional 6 months

6 months

What Are the Treatments Tested in This Trial?

Interventions

• MPH966

Trial Overview The trial is testing alvelestat (MPH966), which may inhibit neutrophil elastase that's thought to contribute to BOS after stem cell transplants. It involves two parts: varying doses over cycles up to 4 months followed by the best dose for up to a year. Participants will undergo extensive monitoring including lung/heart tests and bronchoscopy.

How Is the Trial Designed?

Group I: Phase 2 Experimental Treatment 1 Intervention

MTD po bid on days 1-28

Group II: Phase 1b Experimental Treatment 1 Intervention

Phase Ib dose escalation

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02669251

Alvelestat (MPH966), an Oral Neutrophil Elastase Inhibitor ... Bronchiolitis obliterans syndrome (BOS) is a complication of cGVHD associated with a high morbidity and mortality, and treatment options are limited.

2. mereobiopharma.com mereobiopharma.com/news-and-events/news/2021/december/biomarker-data-from-phase-1b2-investigator-sponsored-trial-of-mereo-s-alvelestat-in-bronchiolitis-obliterans-syndrome-bos-at-the-ash-annual-meeting/

Biomarker Data from Phase 1b/2 Investigator-sponsored ... Treatment with alvelestat was associated with improvement in biomarkers of mechanistic efficacy, with ex vivo zymosan stimulated elastase ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0006497118724373

Phase 1 Study of Alvelestat, an Oral Neutrophil Elastase ... We have demonstrated that NE inhibition is well tolerated and shows a signal of stabilizing disease in patients with advanced BOS.

4. finance.yahoo.com finance.yahoo.com/news/mph966-alvelestat-drug-insight-market-155100797.html

MPH966 (Alvelestat) Drug Insight with Market Projections ... This report offers an in-depth evaluation and projections for MPH966, a novel therapy under development for Bronchiolitis Obliterans Syndrome ( ...

5. mereobiopharma.com mereobiopharma.com/our-pipeline/alvelestat-mph966/

Alvelestat Alvelestat (MPH966) is an oral drug that is being investigated for the treatment of Alpha-1 Antitrypsin Deficiency-associated Lung Disease (AATD-LD).

6. mereobiopharma.com mereobiopharma.com/news-and-events/news/2021/june/mereo-biopharma-announces-positive-desmosine-biomarker-data-from-an-interim-analysis-of-an-investigator-initiated-study-of-alvelestat-in-bronchiolitis-obliterans-syndrome-bos/

Mereo BioPharma Announces Positive Desmosine ... The primary endpoints of the study are to define the safety and the optimal biological dose, based on neutrophil elastase inhibition measured ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT02669251?tab=table

Alvelestat (MPH966), an Oral Neutrophil Elastase Inhibitor ... Bronchiolitis obliterans syndrome (BOS) is a complication people can experience after hematopoietic stem cell transplant. It usually affects people with chronic ...

8. withpower.com withpower.com/trial/alvelestat-for-bronchiolitis-obliterans-syndrome-2f2b5

Alvelestat for Bronchiolitis Obliterans Syndrome This Phase 1 & 2 medical study run by National Cancer Institute (NCI) needs participants to evaluate whether MPH966 will have tolerable side effects ...