Systemic Sclerosis With and Without Interstitial Lung DiseasePhase 1NCT04948554
A Study of MK-2225 / ACE-1334 in Participants With Systemic Sclerosis With and Without Interstitial Lung Disease (MK-2225-002)
A Phase 1 study testing MK-2225 in people with Systemic Sclerosis With and Without Interstitial Lung Disease, run by Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA at 16 sites in 4 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Systemic Sclerosis With and Without Interstitial Lung Disease
- What is being tested?
- MK-2225
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 5 participants
- Where
- 16 sitesin 4 countries
- Study dates
- 10 Mar 2023to 18 Oct 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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
Who cannot join
- 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
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- 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.
Trial locations and contacts
16 sites in 4 countries.
16 sites in 4 countries
United States11 sites
The Cleveland Clinic Foundation ( Site 1003)
Cleveland, Ohio, 44195
Metroplex Clinical Research Center ( Site 1018)
Dallas, Texas, 75231-4446
University of Florida ( Site 1002)
Gainesville, Florida, 32610
Penn State Milton S Hershey Medical Center ( Site 1004)
Hershey, Pennsylvania, 17033
West Tennessee Research Institute ( Site 1012)
Jackson, Tennessee, 38305
University of Kansas Medical Center ( Site 1007)
Kansas City, Kansas, 66160
UCSD Altman Clinical and Translational Research Institute (Site 1013)
La Jolla, California, 92037-0943
Keck Medical Center ( Site 1001)
Los Angeles, California, 90033
Central Florida Pulmonary Group ( Site 1005)
Orlando, Florida, 32803
Medster Research, LLC ( Site 1017)
Valdosta, Georgia, 31605-1096
Georgetown University Medical Center ( Site 1010)
Washington D.C., District of Columbia, 20007
Italy2 sites
Azienda Ospedaliero Universitaria Careggi (Site 1401)
Florence, Tuscany, 50134
Azienda Ospedaliera Universitaria Integrata Di Verona ( Site 1402)
Verona, Veneto, 37134
Switzerland2 sites
Hôpital Neuchatelois ( Site 1304)
Neuchâtel, Neuchâtel (fr), 2000
Kantonsspital St. Gallen (Site 1301)
Sankt Gallen, Canton of St. Gallen, 9000
About this study
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
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.
- Being tested
- MK-2225, Placebo
- Keywords
- Diffuse Systemic Sclerosis, Scleroderma, Systemic Sclerosis, Systemic Sclerosis-associated Interstitial Lung Disease
- Medical subject headings
- Scleroderma, Diffuse, Scleroderma, Systemic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MK-2225Biological
Also called ACE-1334
Administered Subcutaneously (SC)
PlaceboBiological
Administered SC
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1: MK-2225 | Experimental | Participants in Cohort 1 will receive MK-2225 at 0.25 mg/kg once every two weeks (Q2W) plus standard of care (SOC) for 12 weeks. Receives: Biological: MK-2225 |
| Cohort 1: Placebo | Placebo comparator | Participants in Cohort 1 will receive placebo Q2W plus SOC for 12 weeks. Receives: Biological: Placebo |
| Cohort 2: MK-2225 | Experimental | Participants in Cohort 2 will receive MK-2225 at 0.5 mg/kg (or lower) Q2W plus SOC for 12 weeks. Receives: Biological: MK-2225 |
| Cohort 2: Placebo | Placebo comparator | Participants in Cohort 2 will receive placebo Q2W plus SOC for 12 weeks. Receives: Biological: Placebo |
| Cohort 3: MK-2225 | Experimental | Participants in Cohort 3 will receive MK-2225 at 1.0 mg/kg (or lower) Q2W plus SOC for 12 weeks. Receives: Biological: MK-2225 |
| Cohort 3: Placebo | Placebo comparator | Participants in Cohort 3 will receive placebo Q2W plus SOC for 12 weeks. Receives: Biological: Placebo |
| Cohort 4: MK-2225 | Experimental | Participants in Cohort 4 will receive MK-2225 at ≤2.0 mg/kg Q2W if needed plus SOC for 12 weeks. Receives: Biological: MK-2225 |
| Cohort 4: Placebo | Placebo comparator | Participants in Cohort 4 will receive placebo Q2W plus SOC for 12 weeks. Receives: Biological: Placebo |
| Cohort 5: MK-2225 | Experimental | Participants in Cohort 5 will receive MK-2225 (no more frequent than Q2W) ≤2.25 mg/kg Q2W or ≤4.5 mg/kg Q4W if needed plus SOC for 12 weeks. Receives: Biological: MK-2225 |
| Cohort 5: Placebo | Placebo comparator | Participants in Cohort 5 will receive (no more frequent than Q2W) placebo plus SOC for 12 weeks. Receives: Biological: Placebo |
| Cohort 6: MK-2225 | Experimental | Participants in Cohort 6 will receive MK-2225 (no more frequent than Q2W) ≤2.25 mg/kg Q2W or ≤4.5 mg/kg Q4W if needed plus SOC for 12 weeks. Receives: Biological: MK-2225 |
| Cohort 6: Placebo | Placebo comparator | Participants in Cohort 6 will receive (no more frequent than Q2W) placebo plus SOC for 12 weeks. Receives: Biological: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants with ≥1 Adverse Event (AE)
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who experienced an AE will be reported.
Measured: Up to 20 Weeks
Number of Participants Discontinuing from Study Therapy Due to AE
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinued study treatment due to an AE will be reported.
Measured: Up to 12 Weeks
Secondary outcomes (5)
Area Under the Concentration-Time Curve (AUC0-tau) of MK-2225
AUC0-tau is the area under the concentration-time curve. Blood samples will be collected at designated timepoints to determine AUC0-tau of MK-2225.
Measured: Up to 12 Weeks
Serum Maximum Concentration (Cmax) of MK-2225
Cmax is the maximum concentration of the drug observed in plasma. Blood samples will be collected at designated timepoints to determine Cmax of MK-2225.
Measured: Up to 12 Weeks
Time to peak Serum Concentration (Tmax) of MK-2225
Tmax is the amount of time required to reach Cmax. Blood samples will be collected at designated timepoints to determine Tmax of MK-2225.
Measured: Up to 12 Weeks
Serum Apparent Terminal Half-Life (t1/2) of MK-2225
t1/2 is the time required for 50% of drug to be cleared from serum. Blood samples will be collected at designated timepoints to determine t1/2 of MK-2225.
Measured: Up to 12 Weeks
Accumulation ratio of AUCtau (RAUC)
RAUC is the accumulation ratio of AUCtau after multiple doses relative to after a single dose. Blood samples will be collected at designated timepoints to determine RAUC of MK-2225.
Measured: Up to 12 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jul 2021
- Study start10 Mar 2023
- Primary completion18 Oct 2023
- Study completion18 Oct 2023
Why it stopped: Business Reasons
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Systemic Sclerosis With and Without Interstitial Lung DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04948554
- Sponsor's protocol ID
- 2225-002
- Other IDs
- A1334-02, MK-2225-002, 2021-001004-15
- Status last verified
- Nov 2023
- First submitted
- 4 Jun 2021
- Last updated
- 24 Nov 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
Study at a glance
From the registry record, last updated by the sponsor on 24 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04948554
- Acronym / sponsor ID
- 2225-002
- Keywords
- Diffuse Systemic Sclerosis, Scleroderma, Systemic Sclerosis, Systemic Sclerosis-associated Interstitial Lung Disease
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Business Reasons
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USAIndustry (pharma, biotech, devices)
- Study start
- 10 Mar 2023 (actual)
- Primary completion
- 18 Oct 2023 (actual)
- Study completion
- 18 Oct 2023 (actual)
- First posted
- 2 Jul 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Double blind (participant, investigator)
- Number of arms
- 12
| Arm | Type | Receives |
|---|---|---|
| Cohort 1: MK-2225 | Experimental | Biological: MK-2225Participants in Cohort 1 will receive MK-2225 at 0.25 mg/kg once every two weeks (Q2W) plus standard of care (SOC) for 12 weeks. |
| Cohort 1: Placebo | Placebo comparator | Biological: PlaceboParticipants in Cohort 1 will receive placebo Q2W plus SOC for 12 weeks. |
| Cohort 2: MK-2225 | Experimental | Biological: MK-2225Participants in Cohort 2 will receive MK-2225 at 0.5 mg/kg (or lower) Q2W plus SOC for 12 weeks. |
| Cohort 2: Placebo | Placebo comparator | Biological: PlaceboParticipants in Cohort 2 will receive placebo Q2W plus SOC for 12 weeks. |
| Cohort 3: MK-2225 | Experimental | Biological: MK-2225Participants in Cohort 3 will receive MK-2225 at 1.0 mg/kg (or lower) Q2W plus SOC for 12 weeks. |
| Cohort 3: Placebo | Placebo comparator | Biological: PlaceboParticipants in Cohort 3 will receive placebo Q2W plus SOC for 12 weeks. |
| Cohort 4: MK-2225 | Experimental | Biological: MK-2225Participants in Cohort 4 will receive MK-2225 at ≤2.0 mg/kg Q2W if needed plus SOC for 12 weeks. |
| Cohort 4: Placebo | Placebo comparator | Biological: PlaceboParticipants in Cohort 4 will receive placebo Q2W plus SOC for 12 weeks. |
| Cohort 5: MK-2225 | Experimental | Biological: MK-2225Participants in Cohort 5 will receive MK-2225 (no more frequent than Q2W) ≤2.25 mg/kg Q2W or ≤4.5 mg/kg Q4W if needed plus SOC for 12 weeks. |
| Cohort 5: Placebo | Placebo comparator | Biological: PlaceboParticipants in Cohort 5 will receive (no more frequent than Q2W) placebo plus SOC for 12 weeks. |
| Cohort 6: MK-2225 | Experimental | Biological: MK-2225Participants in Cohort 6 will receive MK-2225 (no more frequent than Q2W) ≤2.25 mg/kg Q2W or ≤4.5 mg/kg Q4W if needed plus SOC for 12 weeks. |
| Cohort 6: Placebo | Placebo comparator | Biological: PlaceboParticipants in Cohort 6 will receive (no more frequent than Q2W) placebo plus SOC for 12 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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:
- Male participants must:
- Must agree to not participate in any other study of investigational drugs/devices while enrolled in this study
Key exclusion criteria (17 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MK-2225Also: ACE-1334Administered Subcutaneously (SC) | Biological | Cohort 1: MK-2225, Cohort 2: MK-2225, Cohort 3: MK-2225, Cohort 4: MK-2225, Cohort 5: MK-2225, Cohort 6: MK-2225 |
| PlaceboAdministered SC | Biological | Cohort 1: Placebo, Cohort 2: Placebo, Cohort 3: Placebo, Cohort 4: Placebo, Cohort 5: Placebo, Cohort 6: Placebo |
Primary outcome
Number of Participants with ≥1 Adverse Event (AE)
Time frame: Up to 20 Weeks
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who experienced an AE will be reported.
Number of Participants Discontinuing from Study Therapy Due to AE
Time frame: Up to 12 Weeks
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinued study treatment due to an AE will be reported.
5 secondary outcomes
Area Under the Concentration-Time Curve (AUC0-tau) of MK-2225
Time frame: Up to 12 Weeks
Serum Maximum Concentration (Cmax) of MK-2225
Time frame: Up to 12 Weeks
Time to peak Serum Concentration (Tmax) of MK-2225
Time frame: Up to 12 Weeks
Serum Apparent Terminal Half-Life (t1/2) of MK-2225
Time frame: Up to 12 Weeks
Accumulation ratio of AUCtau (RAUC)
Time frame: Up to 12 Weeks
Results and safety
The study was stopped early (reason given: Business Reasons). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Nov 2023.
- Merck Clinical Trials InformationLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Merck Sharp & Dohme LLC
16 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing MK-2225 in people with Systemic Sclerosis With and Without Interstitial Lung Disease, run by Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA at 16 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 24 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in United States, Italy, Switzerland, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Business Reasons). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants with ≥1 Adverse Event (AE) (time frame: Up to 20 Weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Nov 2023.