Determine effectiveness of Anifrolumab In Systemic sclerosis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Astrazeneca AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17]

Trial duration

24 Nov 2023 → ongoing

Decision date (initial)

2023-10-02

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

AstraZeneca AB

External identifiers

EU CT number

2023-505976-31-00

ClinicalTrials.gov

NCT05925803

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacogenetic, Others, Pharmacokinetic, Therapy, Safety, Efficacy, Pharmacogenomic, Pharmacodynamic

To demonstrate the superiority of anifrolumab to placebo with or without standard therapy on measures of signs, symptoms, and impacts associated with SSc.

Secondary objectives 3

1. To demonstrate the superiority of anifrolumab to placebo in SSc participants: -with or without standard therapy on lung function in participants with SSc-associated interstitial lung disease -on skin thickness
2. To assess the effect of anifrolumab compared with placebo in participants with SSc, with or without standard therapy on: -each component of the measures of signs, symptoms, and impacts associated with SSc -ILD progression as quantified by CT in participants with SSc -Skin-specific HRQOL assessment in participants with SSc -Lung function in participants with SSc -Lung function in participants with SSc-associated ILD
3. To evaluate the Pharmacokinetics, Pharmacodynamics and immunogenicity of SC anifrolumab

Conditions and MedDRA coding

Systemic Sclerosis (SSc) presenting with Limited or Diffuse Cutaneous Subsets

Study design 4 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

IPD plan description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared. AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment https://vivli.org/. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Adult patients from 18 to 70 years of age inclusive
2. Women of childbearing potential with a negative urine pregnancy test
3. Body weight ≤ 145.0 kg (≤ 319.7 lb)
4. Confirmed classification of SSc according to 2013 (American College of Rheumatology/European League Against Rheumatism(ACR/EULAR)) classification criteria
5. Limited or diffuse cutaneous subsets
6. SSc disease duration ≤ 6 years from first non-Raynaud’s phenomenon manifestation at the time of signing the ICF
7. Either Health Assessment Questionnaire Disability Index (HAQ-DI) score ≥ 0.25 points or Patient Global Assessment (PtGA) score≥ 3 points
8. Modified Rodnan Skin Score (mRSS) > 10 with DiseaseDuration <18 months and/or Diagnosis of ILD by Chest CT
9. If a participant does not meet Inclusion Criterion #7, mRSS ≥15 with disease duration ≥ 18 months and active disease at screening with at least one of the following: -Elevated CRP unrelated to other conditions or ESR -New skin involvement/progression by mRSS score change -presence of at least one tendon friction rub within 3 months of screening
10. Stable background therapies can be used including hydroxychloroquine, methotrexate, azathioprine, mycophenolatemofetil, mycophenolic sodium, mycophenolic acid, oralglucocorticoids or tacrolimus
11. Uninvolved skin at injection sites

Exclusion criteria 12

1. Anticentromere antibody seropositivity on central laboratory
2. Major surgery within 8 weeks prior to and/or during study enrollment
3. Known active current or history of recurrent infections
4. Any condition that, in the opinion of the investigator or AstraZeneca, would interfere with efficacy or safety evaluation of the study intervention or put participant at safety risk
5. Severe cardiopulmonary disease as defined by the protocol
6. History of systemic sclerosis renal crisis within past 12 months [Estimated glomerular filtration rate (eGFR) < 45mL/min.]
7. Overlap syndromes, Systemic lupus erythematosus(SLE) with anti-dsDNA antibody seropositivity or Anti-citrullinated protein antibodies-positive (ACPA-positive) rheumatoid arthritis, or SSc mimics (eg, scleromyxedema, eosinophilic fasciitis)
8. History of, or current, any other inflammatory diseases, eg, inflammatory bowel disease, skin disease, that, in the opinion of the investigator, could interfere with efficacy and safety assessments or require immunomodulatory therapy
9. Evidence of moderately severe concurrent nervous system, renal, endocrine, hepatic (eg, underlying chronic liver disease [Child Pugh A, B, C hepatic impairment]), or gastrointestinal disease (eg, clinical signs of malabsorption or needing parenteral nutrition) not related to SSc, as determined by the investigator.
10. Hematopoietic stem cell transplantation or solid organ/limb transplantation
11. Any severe case of Herpes Zoster (HZ) infection as defined by the protocol
12. Known malignancy or a history of malignancy within 5 years, with exception of excised/cured local basal or squamous cell carcinoma of the skin or carcinoma in situ of the uterine cervix

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 5

1. Proportion achieving Revised Composite Response Index in Systemic Sclerosis-25 (Revised-CRISS-25) response where Revised-CRISS-25 is a composite endpoint in which a responder is defined as a participant who meets all the following criteria:
2. Improvement in at least 2 components [≥ 5% increase for Percent predicted forced vital capacity (ppFVC) and/or≥ 25% decrease for mRSS, HAQ-DI, PtGA, Clinician Global Assessment (CGA)
3. Worsening in no more than one component (≥ 5% decrease for ppFVC and/or ≥ 25% increase for mRSS, HAQ-DI, PtGA, CGA)
4. No significant SSc-related event as defined in Step 1 (Khanna et al 2021)
5. Otherwise, a participant is a non-responder

Secondary endpoints 8

1. Treatment related difference in mean change from baseline in pulmonary function
2. Treatment related difference in mean change from baseline in mRSS
3. Treatment related difference in proportion achieving Revised-CRISS-25 components
4. Treatment related difference in proportion achieving interstitial lung disease progression
5. Treatment related difference in patient reported outcomes based on the Scleroderma Skin patient reported outcome
6. Evaluate the pharmacokinetics (PK), pharmacodynamics (PD) and immunogenicity of subcutaneous Anifrolumab
7. Treatment related difference in safety and tolerability with or without standard therapy in participants with SSc
8. Long term treatment related difference in safety and tolerability with or without standard therapy in participants with SSc

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Astrazeneca AB

Sponsor organisation

Astrazeneca AB

Address

Astraallen Gartuna, Karlebyhus Byggnad 674 Karlebyhus Byggnad 674

City

Sodertalje

Postcode

151 85

Country

Sweden

Scientific contact point

Organisation

Astrazeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Public contact point

Organisation

Astrazeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Locations

10 EU/EEA countries · 64 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Serious breaches 1 · Art. 52 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 123 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

17 submissions — initial application plus substantial / non-substantial modifications