Double-blind, randomized, placebo-controlled study on the efficacy and safety of "PRA023" in patients with systemic sclerosis associated with interstitial lung disease

Australia, Belgium, Canada, France, Germany, Hungary, Israel, Italy, Netherlands, Norway, Poland, Spain, Switzerland, United Kingdom, United States (ICTRP)

ICTRP Trial ID
EUCTR2021-005206-10 (ICTRP)

Official title (approved by ethics committee)
A Double Blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy and Safety of MK-7240/PRA023 in Subjects with Systemic Sclerosis Associated with Interstitial Lung Disease (SSc-ILD) (BASEC)

Academic title
A Double Blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy and Safety of MK-7240/PRA023 in Subjects with Systemic Sclerosis Associated with Interstitial Lung Disease (SSc-ILD) - The ATHENA-SSc-ILD Study (ICTRP)

Public title
A study of MK-7240/PRA023 in patients with Systemic Sclerosis Associated with Interstitial Lung Disease (ICTRP)

Disease under investigation
Systemic sclerosis associated with interstitial lung disease
MedDRA version: 21.0Level: LLTClassification code 10025109Term: Lung involvement in systemic sclerosisSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders;Therapeutic area: Diseases [C] - Immune System Diseases [C20] (ICTRP)

Intervention under investigation

Product Code: MK-7240/PRA023
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: tulisokibart
CAS Number: 2648504-55-4
Current Sponsor code: MK-7240/PRA023
Other descriptive name: MK-7240/PRA023
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 60-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

(ICTRP)

Type of trial
Interventional clinical trial of medicinal product (ICTRP)

Trial design
Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2 (ICTRP)

Inclusion/Exclusion criteria
Gender:
Female: yes
Male: yes

Inclusion criteria:
1.Male or female = 18 years of age.
2.Subjects must meet the 2013 ACR/EULAR definition of SSc.
3.Subjects must have had SSc onset (defined by first non-Raynaud symptom) = 5 years (60 months) prior to screening.
4.Subjects must have diffuse cutaneous scleroderma defined as any level of skin thickening proximal to the elbows and knees exclusive of the face and neck. Total mRSS must be 10 to 35 units, inclusive.
5.Subjects must have SSc-related ILD of fibrotic disease in lung confirmed by HRCT = 10% extent of involvement, assessed by central reading.
6.FVC 45% of predicted normal.
7.Diffusing capacity of lung for carbon monoxide (DLCO) ? 45% of predicted normal (corrected for hemoglobin [Hgb]).
8.Meet at least one of the following criteria:
a. C-reactive protein (CRP) > upper limit of normal (ULN)
b. Erythrocyte sedimentation rate (ESR) > 28 mm/hr
c. Positive for anti-topoisomerase (anti-Scl-70) antibody
9.Background therapy is not required, but subjects receiving background therapy must meet drug stabilization requirements, as applicable:
a. Either mycophenolate mofetil (not to exceed 3 g/day) or oral or subcutaneous methotrexate (not to exceed 25 mg/week) or azathioprine (not to exceed 150 mg/day) for = 4 months prior to randomization (not more than 1 therapy) and on a stable dose for 4 weeks prior to randomization
b. Subjects who have been on nintedanib for = 6 months (and stable dose for at least 4 weeks) prior to randomization may enter the study provided that there has not been any improvement in FVC (% and absolute) from prior to the initiation of nintedanib therapy
c. A stable dose of oral corticosteroids (= 10 mg/day prednisone equivalent) for 2?weeks prior to randomization. Inhaled and topical corticosteroids are permitted.
10. A female subject is eligible to participate if not pregnant or breastfeeding, and at least one of the following conditions applies:
? Is not a woman of childbearing potential (WOCBP) OR
? Is a WOCBP and:
- Uses an acceptable contraceptive method, or is abstinent from penilevaginal intercourse as their preferred and usual lifestyle (abstinent on a
long-term and persistent basis),from at least 4 weeks prior to Day 1/Week 0, during the intervention period, and for at least 12 weeks after
the last dose of study intervention. The Investigator should evaluate the potential for contraceptive method failure (i.e., noncompliance, recently
initiated) in relationship to the first dose of study intervention.
Contraceptive use by WOCBP should be consistent with local regulations regarding the methods of contraception for those participating in clinical
studies. For any background medications, the local label should be followed for contraception.
- Has a negative highly sensitive pregnancy test (urine or serum) as required by local regulations within 24 hours (for a urine test) or 72
hours (for a serum test) before the first dose of study intervention. If a urine test cannot be confirmed as negative (e.g., an ambiguous result), a
serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
- Medical history, menstrual history, and recent sexual activity has been reviewed by the investigator to decrease the risk for inclusion of a WOCBP with an early undetected pregnancy
11.Able to provide written informed consent and understand and comply with the requirements of the study.
Are the trial subjects under 18? no
Number of su (ICTRP)

Exclusion criteria:
1.Subjects with a history of cancer within the last 5 years (other than non-melanoma skin cell cancers cured by local resection or cervical carcinoma in situ). Existing non-melanoma skin cell cancers must be removed prior to enrollment. Subjects with carcinoma in situ or localized cervical cancer, treated with definitive surgical intervention, are allowed.
2. Subject has active TB or meets TB exclusionary parameters
3.Subjects with chronic or recurrent infection (such as chronic pyelonephritis, osteomyelitis, and bronchiectasis).
4. Subjects with any active infections (excluding fungal infections of nail beds) including, but not limited to, those that require IV or IM antimicrobial treatment 4 weeks or oral antimicrobial treatment 2 weeks prior to randomization.
5.Subjects known to be infected with HBV, HCV, or HIV
? Participants with positive HBsAg are excluded from the study.
Participants with negative HBsAg and positive HBcAb must have further testing for HBV-DNA. Participants with HBV-DNA =LLOQ are not eligible
for the study. Participants with HBV-DNA ? Participants with positive HCV Abs at Screening must have further testing for HCV RNA. Participants with HCV RNA =LLOQ are not eligible for the study. Participants with positive HCV Abs but HCV RNA ? Participants with a history of HIV infection or who have a positive Ab test are not eligible for the study.
6. Subjects with confirmed or suspected COVID-19 infection. Note: Subjects with recent confirmed or suspected COVID-19 infection may participate under the following conditions:
? Subjects with COVID-19 infection confirmed by a PCR or an antigen
test:
- For asymptomatic subjects, randomization must be at least 10 days after the positive COVID-19 test.
- For symptomatic subjects, randomization must be at least 10 days after onset of symptoms and at least 3 days after resolution of fever without
the use of fever-reducing medications, and the participant must have a clinically meaningful improvement in symptoms.
? Subjects with suspected COVID-19 infection:
- For subjects with signs/symptoms suggestive of COVID-19 infection, a molecular (i.e., PCR) test must be performed to rule out COVID-19 infection before randomization.
OR
- Randomization must be at least 10 days after onset of symptoms and at least 3 days after resolution of fever without the use of fever-reducing
medications, and the participant must have clinically meaningful improvement in symptoms
7. Treatment with:
a.Tofacitinib, upadacitinib, baricitinib, abrocitinib, or filgotinib within 4 weeks of randomization
b.D-penicillamine, sulfasalazine, cyclosporine, or pirfenidone within 8 weeks of randomization
c.Cyclophosphamide, tocilizumab, abatacept, leflunomide, tacrolimus, or any other approved biologics for rheumatic diseases within 3 months of
randomization
d.Intravenous immunoglobulin within 5 months of randomization
e.Rituximab within 6 months of randomization.
8. Prior exposure to MK-7240/PRA023 or other TL1A antagonists.


Primary and secondary end points
Main Objective: ? To assess the safety and tolerability of MK-7240/PRA023 in SSc-ILD
? To compare the annual rate of change from Baseline in forced vital capacity (FVC) in mL of MK-7240/PRA023 vs. placebo over 50 weeks;Secondary Objective: ? To compare the change from Baseline in FVC in mL of MK7240/PRA023 vs. placebo at Week 50
? To compare the change from Baseline in high-resolution computer tomography (HRCT) quantitative interstitial lung disease ? whole lung (QILD-WL) of MK-7240/PRA023 vs. placebo at Week 50
? To compare proportion of subjects with an improvement in the revised Composite Response Index in Systemic Sclerosis (CRISS) score of MK7240/PRA023 vs. placebo at Week 50
? To assess the change from Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) of MK-7240/PRA023 vs. placebo at Week 50
? To assess the change from Baseline in Living with Pulmonary Fibrosis (L-PF) patient-reported quality of life (QoL) outcome of MK7240/PRA023 vs. placebo at Week 50;Primary end point(s): _ The proportion of subjects reporting adverse events (AEs), serious adverse events (SAEs), AEs leading to discontinuation, and markedly
abnormal laboratory values
_ To compare the annual rate of change from Baseline in FVC in mL of MK-7240/PRA023 vs. placebo over 50 weeks ;Timepoint(s) of evaluation of this end point: Week 50 (ICTRP)

Secondary end point(s): To compare the change from Baseline in FVC in mL of MK-7240/PRA023 vs. placebo at Week 50
? To compare the change from Baseline in HRCT QILD-WL of MK7240/PRA023 vs. placebo at Week 50
? To compare proportion of subjects with an improvement in the revised CRISS score of MK-7240/PRA023 vs. placebo at Week 50
? To assess the change from Baseline in HAQ-DI of MK-7240/PRA023 vs. placebo at Week 50
? To assess the change from Baseline in L-PF patient-reported quality of life (QoL) outcome of MK-7240/PRA023 vs. placebo at Week 50;Timepoint(s) of evaluation of this end point: Week 50 (ICTRP)

Registration date
16.03.2022 (ICTRP)

Incorporation of the first participant
01.08.2022 (ICTRP)

Secondary sponsors
not available

Additional contacts
Clinical Operations, AthenaMM@prometheusbiosciences.com, Prometheus Biosciences, Inc., a subsidiary of Merck & Co,. Inc.(Rahway, NJ, USA). (ICTRP)

Secondary trial IDs
PR200-104(MK-7240-007), NCT05270668, 2021-005206-10-FR (ICTRP)

Results-Individual Participant Data (IPD)
not available

Further information on the trial
https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2021-005206-10 (ICTRP)