MPH966 for Prevention of Graft-versus-host Disease After Allogeneic Hematopoietic Stem Cell Transplantation

NCT03986086 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: Pro00102362
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is evaluate the safety and tolerability of MPH966, a neutrophil elastase inhibitor, and its ability to prevent graft-versus-host disease after hematopoietic stem cell transplant.

Conditions

Hematologic Malignancy

Outcome Measures

Primary Outcomes (1)

• Incidence of grade 2-4 acute Graft vs Host Disease (GVHD) requiring systemic therapy

  day 100

Secondary Outcomes (74)

• Incidence of grade 2-4 acute GVHD

  day 100

• Incidence of grade 3-4 acute GVHD

  day 100

• Incidence of grade 2-4 acute GVHD

  month 6

• Incidence of grade 3-4 acute GVHD

  month 6

• Kaplan-Meier analysis of time-to-event: percentage of participants who develop grade 2-4 acute GVHD by visit

  day 0 and 100 days, 6 months

Study Arms (2)

MPH966

EXPERIMENTAL

Participants receive MPH966 at RP2D tablet orally twice daily from the start of conditioning chemotherapy through 45 days post transplant.

Drug: MPH966

Placebo

PLACEBO COMPARATOR

Participants receive MPH placebo tablet matching MPH966 orally twice daily from the start of conditioning chemotherapy through 45 days post transplant.

Drug: Placebo

Interventions

MPH966 DRUG

RP2D tablet

Also known as: alvelestat

MPH966

Placebo DRUG

MPH966 placebo table

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of written informed consent prior to any study specific procedures
• Plan to undergo allogeneic HCT for any cancer or non-cancer illness with a planned cell dose of ≥2 x 106 CD34/kg using peripheral blood stem cells.
• Plan to receive a myeloablative conditioning regimen (see 4.3.1).
• Plan to receive GVHD prophylaxis with tacrolimus and methotrexate.
• Having a donor who is a 10 of 10 HLA match;
• Karnofsky Performance Scale KPS ≥60
• Willing to abstain from sexual activity or use two methods of birth control while on study drug and for 5 half-lives (4 days) after last dose.

You may not qualify if:

• If female, pregnant or nursing.
• Life expectancy \<6 months
• Other malignancy or neoplastic disease (i.e. aside from the malignancy for which they are undergoing HCT) within the past 5 years with the exception of treated basal/squamous cell skin carcinoma or treated cervical cancer in situ
• Clinically significant active infection within 1 week of starting study drug
• Any of the following organ system function criteria:
• Cardiac: Ejection fraction ≤40% or myocardial infarction within 6 months of transplant or QTc \>450 msec for males and \>470 msec for females or other EKG abnormality which in the opinion of the investigator may put the subject at risk or interfere with study assessments
• Renal: Creatinine clearance (CLcr) ≤ 60 mL/min as estimated by the Cockcroft-Gault equation
• Pulmonary: FEV1, FVC, or corrected DLCO ≤40% predicted (forced expiratory volume in 1 second; forced vital capacity; and diffusing capacity of the lung for carbon monoxide, respectively)
• Uncontrolled infection, including detection of hepatitis B virus (HBV) or hepatitis C virus (HCV) by serology or nucleic acid testing or HIV by polymerase chain reaction (PCR)
• i. Treated HBV/HCV/HIV with documented clearance is ok f. Other significant organ dysfunction (cardiac, pulmonary, renal, metabolic or central nervous system) that is uncontrolled and may interfere with study completion
• Any significant medial history of alcohol abuse within 3 months of starting study drug and/or unwillingness to abstain for the duration of the study and follow up periods
• Prior (within 30 days) or concomitant use of another neutrophil elastase inhibitor (e.g. alpha-1 antitrypsin)
• Plan for in vivo or ex vivo T cell depletion.
• Participated in another clinical study involving an investigational drug or device within 30 days or 5 half-lives prior to planned start of MPH966/placebo, or scheduled to participate in another clinical study involving an investigational drug or device within Day 100 of transplant
• If the patient develops GVHD within the first 100 days, they are allowed to enroll on trials of investigational drugs to treat GVHD provided they come off of this study.

Sponsors & Collaborators

• Nelson Chao: lead
• Mereo BioPharma: collaborator
• National Center for Advancing Translational Sciences (NCATS): collaborator

Study Sites (1)

Duke University Adult Bone Marrow Transplant Clinic

Durham, North Carolina, 27705, United States

Location

MeSH Terms

Conditions

Hematologic Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Anthony Sung, MD

  Duke University Health System (DUHS)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Donald D. and Elizabeth G. Cooke Cancer Research Professor

Study Record Dates

• First Submitted: June 12, 2019
• First Posted: June 14, 2019
• Study Start: September 1, 2021
• Primary Completion: December 1, 2022
• Study Completion: December 1, 2023
• Last Updated: March 20, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)