Phase 2 study comparing SAR447537 to plasma-derived A1PI therapy for AATD emphysema

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Sanofi AATD Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08], Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Trial duration

31 May 2024 → 6 Aug 2025

Decision date (initial)

2024-04-24

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Inhibrx Inc.

External identifiers

EU CT number

2023-508084-76-00

WHO UTN

U1111-1309-9066

ClinicalTrials.gov

NCT05856331

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Dose response, Pharmacokinetic, Pharmacodynamic, Therapy, Efficacy

To evaluate the pharmacodynamic effect on serum trough functional AAT (fAAT) levels at steady-state, following a treatment period of up to 32-weeks, in participants with AATD emphysema treated with SAR447537 compared to A1PI

Secondary objectives 1

1. To assess serum pharmacokinetics (PK) and pharmacodynamic (PD) effect of SAR447537 and A1PI on serum average fAAT levels • To evaluate safety and tolerability of SAR447537 and A1PI • To assess immunogenicity of SAR447537 and A1PI

Conditions and MedDRA coding

Alpha-1 Antitrypsin Deficiency (AATD) Emphysema

Study design 1 period

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

IPD plan description

Plan Description:​ Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: vivli.org​

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 1. Males or females 18-80 years of age, inclusive, at the time of screening 2. Diagnosis of AATD 3. Evidence of emphysema secondary to AATD 4. FEV1 of ≥ 30% and ≤ 80% predicted at screening 5. Current non-smoking status.

Exclusion criteria 1

1. 1. Receipt of A1PI augmentation therapy within 5 weeks prior to the first dose of study drug 2. Known or suspected allergy to components of SAR447537, A1PI or human IgG 3. Known selective or severe Immunoglobulin A (IgA) deficiency 4. Known or suspected diagnosis of type 1 diabetes or diagnosed with uncontrolled type 2 diabetes 5. Received IV immunoglobulins, monoclonal antibodies and/or other biologic therapies within 30 days 6. On waiting list for lung or liver transplant 7. Acute respiratory tract infection or COPD exacerbation within 4 weeks prior to or during screening 8. Evidence of decompensated cirrhosis 9. Active cancers or has a history of malignancy within 5 years prior to screening 10. History of unstable cor pulmonale 11. Clinically significant congestive heart failure

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Mean change in average fAAT concentration as measured by anti-neutrophil elastase capacity [ANEC] from baseline to average serum trough fAAT concentration at steady state (Ctrough,ss) in participants treated with SAR447537 compared to A1PI

Secondary endpoints 3

1. 1. Mean change in serum fAAT concentration from baseline to fAAT average concentration at steady state (Cavg,ss) in participants treated with INBRX-101 compared to A1PI 2. Percentage of days with fAAT above the lower limit of the normal range during steady-state dosing in participants treated with INBRX-101 compared to A1PI
2. 3. Incidence of all treatment emergent adverse events (TEAEs), TEAEs ≥ Grade 3, serious adverse events (SAEs), TEAEs leading to IMP discontinuation, adverse events of special interest (AESI) (including infusion-related reactions)
3. 4. Frequency of anti-drug antibodies (ADA) against SAR447537 and endogenous AAT, as well as neutralizing ADA (NAb) against SAR447537 and endogenous AAT 5. Population PK modeling to assess impact of physiologically relevant patient participants characteristics (eg, covariates including, but not limited to, age, sex, body size, ethnicity) and disease on PK

Investigational products

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

Test 1

Comparator 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Sanofi AATD Inc.

Sponsor organisation

Sanofi AATD Inc.

Address

450 Water Street

City

Cambridge

Postcode

02141-2288

Country

United States

Scientific contact point

Organisation

Sanofi AATD Inc.

Contact name

Clinical Sciences and Operations

Public contact point

Organisation

Sanofi AATD Inc.

Contact name

Clinical Sciences and Operations

Third parties 12

Locations

5 EU/EEA countries · 9 investigational sites

By country

Investigational sites

Country notifications

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

Results and documents

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

Documents 84 files

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

Application history

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