Clinical trial NCT04948554: A Study of MK-2225 / ACE-1334 in Participants With Systemic Sclerosis With and Without Interstitial Lung Disease (MK-2225-002)
Official title: A Phase 1b Randomized, Double-Blind, Placebo-Controlled, Multiple-Ascending Dose Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of ACE-1334 Plus Standard of Care in Participants With Systemic Sclerosis
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Systemic Sclerosis With and Without Interstitial Lung Disease
Keywords: Diffuse Systemic Sclerosis
Scleroderma
Systemic Sclerosis
Systemic Sclerosis-associated Interstitial Lung Disease
Lead sponsor: Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA
Sponsor class: INDUSTRY
First posted: 2021-07-02
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The purpose of the MK-2225-002 (A1334-02) study is to evaluate the safety and tolerability of MK-2225 (ACE-1334) plus standard of care (SOC) in participants with Systemic Sclerosis (SSc) following multiple doses.


Eligibility criteria: The main inclusion and exclusion criteria include but are not limited to the following:

Inclusion Criteria:

* Participants must have SSc, as defined using the 2013 American College of Rheumatology/European League Against Rheumatism criteria
* If participant is on a non-excluded immunosuppressive therapy (e.g. mycophenolate, methotrexate, azathioprine, etc.) the dose should be stable for \> 2 months at the time of screening
* Women of childbearing potential must:

  * If sexually active, have used, and agree to use, highly effective contraception without interruption, for at least 28 days prior to starting investigational product, during the study (including dose interruptions), and for 17 weeks (119 days) after discontinuation of study treatment
  * Refrain from breastfeeding a child or donating blood, eggs, or ovum for the duration of the study and for at least 17 weeks (119 days) after the last dose of study treatment
* Male participants must:

  * Agree to use a condom, defined as a male latex condom or nonlatex condom NOT made out of natural (animal) membrane (e.g., polyurethane), during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions, and for at least 17 weeks (119 days) following investigational product discontinuation, even if he has undergone a successful vasectomy
  * Refrain from donating blood or sperm for the duration of the study and for 17 weeks (119 days) after the last dose of study treatment
* Must agree to not participate in any other study of investigational drugs/devices while enrolled in this study

Exclusion Criteria:

* Participant with SSc-pulmonary arterial hypertension (PAH) (except those participants with mild PAH on up to 2 oral drugs and mean pulmonary arterial pressure \< 30 mmHg or low risk by risk calculator)
* In the opinion of the investigator, other clinically significant pulmonary abnormalities (such as obstructive lung disease, asthma, etc.)
* Other investigational therapy received within 1 month or 6 half-lives (whichever is greater) prior to the Screening Visit
* Prior exposure to MK-2225 or other TGF-β antibodies or any TGF-β family targeted biologic or hypersensitivity to the components of MK-2225
* Hypersensitivity to placebo or any of its components
* Previous hematopoietic stem cell transplantation (HSCT) or HSCT planned within the next year
* Major surgical procedures planned during the study period
* Oral prednisone or equivalent \> 10 mg/day
* Participant with history of gastric antral vascular ectasia or gastrointestinal bleed
* On anticoagulation therapy (such as prophylaxis anticoagulation, warfarin, direct thrombin inhibitors or other including low molecular weight subcutaneous or intravenous therapeutic heparin), or antiplatelet therapy including aspirin. Use of fish oil supplements within 2 weeks prior to randomization and throughout study is not permitted.
* History of any other medical condition that might interfere with a participant's ability to participate in the study
* Active clinically significant viral, bacterial, or fungal infection, or any episode of infection requiring hospitalization within 4 weeks prior to screening
* Use of cyclophosphamide ≤ 6 months from screening
* Use of nintedanib or pirfenidone ≤ 28 days from screening
* Recent scleroderma renal crisis \< 6 months before screening
* Use of tocilizumab ≤ 2 months from screening
* Has received any nonlive vaccine starting from 14 days prior to study intervention or is scheduled to receive any nonlive vaccine through 30 days following study intervention. Exception: COVID-19 vaccine may be administered.

Primary outcomes:
measure: Number of Participants with ≥1 Adverse Event (AE)
timeFrame: Up to 20 Weeks
measure: Number of Participants Discontinuing from Study Therapy Due to AE
timeFrame: Up to 12 Weeks
Secondary outcomes:
measure: Area Under the Concentration-Time Curve (AUC0-tau) of MK-2225
timeFrame: Up to 12 Weeks
measure: Serum Maximum Concentration (Cmax) of MK-2225
timeFrame: Up to 12 Weeks
measure: Time to peak Serum Concentration (Tmax) of MK-2225
timeFrame: Up to 12 Weeks
measure: Serum Apparent Terminal Half-Life (t1/2) of MK-2225
timeFrame: Up to 12 Weeks
measure: Accumulation ratio of AUCtau (RAUC)
timeFrame: Up to 12 Weeks
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: UCSD Altman Clinical and Translational Research Institute (Site 1013)
state: California
city: Los Angeles
country: United States
facility: Keck Medical Center ( Site 1001)
state: California
city: Washington
country: United States
facility: Georgetown University Medical Center ( Site 1010)
state: District of Columbia
city: Gainesville
country: United States
facility: University of Florida ( Site 1002)
state: Florida
city: Orlando
country: United States
facility: Central Florida Pulmonary Group ( Site 1005)
state: Florida
city: Valdosta
country: United States
facility: Medster Research, LLC ( Site 1017)
state: Georgia
city: Kansas City
country: United States
facility: University of Kansas Medical Center ( Site 1007)
state: Kansas
city: Cleveland
country: United States
facility: The Cleveland Clinic Foundation ( Site 1003)
state: Ohio
city: Hershey
country: United States
facility: Penn State Milton S Hershey Medical Center ( Site 1004)
state: Pennsylvania
city: Jackson
country: United States
facility: West Tennessee Research Institute ( Site 1012)
state: Tennessee
city: Dallas
country: United States
facility: Metroplex Clinical Research Center ( Site 1018)
state: Texas
city: Toronto
country: Canada
facility: Mount Sinai Hospital ( Site 1101)
state: Ontario
city: Florence
country: Italy
facility: Azienda Ospedaliero Universitaria Careggi (Site 1401)
state: Tuscany
city: Verona
country: Italy
facility: Azienda Ospedaliera Universitaria Integrata Di Verona ( Site 1402)
state: Veneto
city: Neuchâtel
country: Switzerland
facility: Hôpital Neuchatelois ( Site 1304)
state: Neuchâtel (fr)
city: St Gallen
country: Switzerland
facility: Kantonsspital St. Gallen (Site 1301)
state: Sankt Gallen
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: