Clinical trial NCT06967805: WISPer: Evaluation of MTX-463 in Participants With Idiopathic Pulmonary Fibrosis (IPF)
Official title: A Phase 2 Randomized, Double-blind, Placebo-controlled Study of the Safety and Efficacy of MTX-463 in Participants With Idiopathic Pulmonary Fibrosis (IPF)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Idiopathic Pulmonary Fibrosis
Keywords: MTX-463-I201
MTX-463
IPF
Idiopathic Pulmonary Fibrosis
Adult
Fibrosis
Monoclonal Antibody
MAB
FVC
WISPer
Lead sponsor: Mediar Therapeutics
Sponsor class: INDUSTRY
First posted: 2025-05-13
Enrollment: 164
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A Phase 2a, Randomized, Double-blind, Placebo-Controlled Study of the Safety and Efficacy of MTX-463 in Participants with Idiopathic Pulmonary Fibrosis (IPF)

Detailed description: Participants with IPF who meet the study's inclusion and exclusion criteria will be randomly assigned in a 1:1 ratio to receive MTX-463 or a matching placebo by intravenous (IV) infusion. Concomitant use of one of the approved IPF therapies, pifenidone or nintedanib, is permitted, and it is expected that about half the study population will be on one of those medications. Participants randomized to the MTX-463 arm of the study will receive an IV infusion every 4 weeks, beginning at Day 0 and ending at Week 20. The End of Treatment Visit will occur at Week 24, 4 weeks after the final infusion; and a final Safety Follow-Up Visit will occur at Week 28, 8 weeks after the final infusion. Assessments of FVC will occur at Screening, Baseline, and at all subsequent treatment visits up to and including Week 24. L-PF assessments will be performed at Baseline and Week 24. Participants will have blood drawn for safety assessment and to assess WISP1 levels at Baseline and every 4 weeks throughout the study. Blood will be drawn for serum PK analyses relative to the first and last doses of MTX-463.

Eligibility criteria: Inclusion Criteria:

* Participants with IPF of any gender ≥ 40 years of age at time of signing the informed consent.
* Able to understand the study and provide signed, written informed consent.
* Able to read and understand the language of the informed consent and other trial-related materials.
* Meet the American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Latin American Thoracic Association (ATS/ERS/JRS/ALAT) 2019 criteria for the diagnosis of IPF; Diagnosed with IPF within 7 years of screening.
* If a participant is on treatment with pirfenidone or nintedanib, the dose of the medication must be stable for ≥ 90 days prior to Screening with plans to maintain the same dose throughout the study treatment period. Use of both agents together is not permitted.
* If a participant was on treatment with nintedanib or pirfenidone, and the agent has been discontinued, this must have occurred ≥ 30 days prior to Screening. At Screening, there must also be no plan to start either of these medications for the duration of the study.
* FVC of ≥ 45 percent predicted (pp) at screening.
* DLCO of ≥ 25pp at screening.
* Willing and able to complete all protocol required study visits and procedures.
* All participants of childbearing potential must have a negative serum pregnancy test at Screening.
* Participants with reproductive potential must agree to use and follow medically approved contraceptive precautions during the study

Exclusion Criteria:

* Acute exacerbation of IPF within 6 months of Screening or during the Screening Period.
* Forced expiratory volume in 1 second (FEV1)/FVC ratio of \<0.7 at Screening.
* Requirement for continuous supplemental oxygen. Intermittent supplemental oxygen use (e.g., during exercise or sleep) is permitted.
* Expected to receive a lung transplant within the study duration.
* Current active bacterial infection or use of antibiotics for suspected lung infection in the 30 days prior to Screening.
* Planned surgery within the study duration.
* Clinically significant pulmonary hypertension.
* Use of immunosuppressive therapy (excluding corticosteroids). If previously on such agents, they should have been discontinued for at least 5 half-lives or 90 days, whichever is longer, prior to Screening.
* Use of systemic corticosteroids (prednisone or equivalent) at a dose ≥ 10 mg once daily within 30 days of Screening.
* Currently smoking or vaping.
* Current known malignancy, or history of cancer, or lymphoproliferative disorder other than non-melanomatous skin cancers, within 2 years of Screening.
* Current infection with hepatitis B, hepatitis C, or human immunodeficiency virus (HIV).
* Currently pregnant, breast feeding, or planning to conceive for the length of the study.
* History of severe depression, psychosis, or suicidal ideation, as determined by the Investigator, within 2 years of Screening.
* Any clinically significant disease or laboratory abnormality detected at Screening that might interfere with a participant's ability to complete the study, on-study evaluations, or participant safety.
* Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 2× upper limit of normal (ULN) at Screening.
* Any other concurrent active medical condition determined by the Investigator to interfere with participant's ability to complete the trial.
* Known allergy to MTX-463 or any of its excipients.
* Any prior use of MTX-463 or other therapy targeting WISP1.
* Any other concurrent experimental agent or an active part of any other clinical trial, unless they have stopped taking the investigational product at least 5 half-lives or 30 days before Screening, whichever is longer.

Primary outcomes:
measure: To assess the effect of MTX-463 on the change from Baseline in forced vital capacity (FVC)
timeFrame: 24 Weeks
Secondary outcomes:
measure: To assess the safety and tolerability of MTX-463 in participants with IPF, as measured by incidence of treatment emergent adverse events
timeFrame: 28 Weeks
measure: To assess the safety and tolerability of MTX-463 in participants with IPF, as measured by incidence of treatment related adverse events
timeFrame: 28 Weeks
measure: To assess the safety and tolerability of MTX-463 in participants with IPF, as measured by incidence of serious treatment emergent adverse events
timeFrame: 28 Weeks
measure: To assess the safety and tolerability of MTX-463 in participants with IPF, as measured by incidence of severe treatment emergent adverse events
timeFrame: 28 Weeks
measure: To assess the safety and tolerability of MTX-463 in participants with IPF, as measured by incidence of treatment emergent abnormalities on clinical laboratory tests
timeFrame: 28 Weeks
measure: To assess the safety and tolerability of MTX-463 in participants with IPF, as measured by incidence of abnormal findings on physical exam
timeFrame: 28 Weeks
measure: To assess the safety and tolerability of MTX-463 in participants with IPF, as measured by incidence of treatment discontinuations
timeFrame: 28 Weeks
measure: To assess the effect of MTX-463 on the change from Baseline in the percent predicted FCV (FVCpp)
timeFrame: 24 Weeks
measure: To collect sparse pharmacokinetics (PK) of MTX-463 in participants with IPF
timeFrame: 24 Weeks
Other outcomes:
measure: To assess the development of antidrug antibodies (ADA) against MTX-463
timeFrame: 28 Weeks
measure: To assess the effect of MTX-463 on the change from Baseline in FVC in participants on concomitant nintedanib or pirfenidone
timeFrame: 24 Weeks
measure: To assess the effect of MTX-463 on the change from Baseline in FVC in participants not on concomitant nintedanib or pirfenidone
timeFrame: 24 Weeks
measure: To assess the effect of MTX-463 on the change from Baseline in the Living with Pulmonary Fibrosis (L-PF) Questionnaire total score
timeFrame: 24 Weeks
measure: To assess whether serum WNT-inducible signaling pathway protein 1 (WISP1) levels at Screening predict improved outcomes with MTX-463 treatment
timeFrame: 24 Weeks
measure: To assess the effect of MTX-463 on the change from Baseline in percent predicted diffusing capacity of the lungs for carbon monoxide (DLCO)
timeFrame: 24 Weeks
measure: To evaluate the time to disease progression as determined by change in FVC, IPF-related changes, or death
timeFrame: 28 Weeks
measure: To assess the effect of MTX-463 on Pro-C3
timeFrame: 24 Weeks
measure: To assess the effect of MTX-463 on interleukin-6
timeFrame: 24 Weeks
Locations:
city: Newport Beach
country: United States
facility: WISPer site in Newport Beach, CA
state: California
city: Loxahatchee
country: United States
facility: WISPer site in Loxahatchee, FL
state: Florida
Study officials:
affiliation: Mediar Therapeutics
name: Pablo Zertuche, MD
role: STUDY_CHAIR
References: