Long-term, open-label study of SAR447537 (INBRX-101) in adults with alpha-1 antitrypsin deficiency 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] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16], Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

11 Mar 2025 → ongoing

Decision date (initial)

2024-09-19

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Inhibrx Inc.

External identifiers

EU CT number

2023-508137-14-00

WHO UTN

U1111-1310-5249

ClinicalTrials.gov

NCT05897424

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Efficacy, Therapy, Others

To evaluate the long-term safety and tolerability of SAR447537.

Secondary objectives 3

1. To evaluate the change in lung density by quantitative computerized tomography (qCT).
2. To assess serum pharmacokinetics (PK) of SAR447537 and functional AAT (fAAT).
3. To assess immunogenicity of SAR447537.

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: https://vivli.org​

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

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% predicted at screening and post-bronchodilator FEV1/FVC<0.7.
5. Current non-smoking status.

Exclusion criteria 9

1. For Newly Identified Participants: 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. Received IV immunoglobulins, monoclonal antibodies and/or other biologic therapies within 30 days.
4. On waiting list for lung or liver transplant.
5. Acute respiratory tract infection or COPD exacerbation within 4 weeks prior to or during screening.
6. Evidence of decompensated cirrhosis.
7. Active cancers or has a history of malignancy within 5 years prior to screening.
8. History of unstable cor pulmonale.
9. Uncontrolled diabetes mellitus despite adequate antidiabetic pharmacologic treatment with a screening HbA1c value ≥9%

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Incidences of all treatment-emergent adverse events (TEAEs), TEAEs ≥Grade 3, serious adverse events (SAEs), TEAEs requiring withdrawal from investigational product (IP) treatment leading to discontinuation from SAR447537, and adverse events of special interest (AESIs) (including infusion-related reactions) leading to discontinuation from and adverse events of special interest (AESIs) (including infusion-related reactions).

Secondary endpoints 4

1. Annual rate of change in lung density assessed by serial quantitative CT (15th percentile point [PD15]) at total lung capacity (TLC), centrally read, from Baseline to End of Treatment (EoT).
2. Serum PK profile of SAR447537 and fAAT.
3. Population PK modeling to assess impact of physiologically relevant participant characteristics (eg, covariates including, but not limited to, age, sex, body size, ethnicity) and disease on PK of SAR447537 through Population PK modeling.
4. Incidence of anti-drug antibodies (ADAs) against SAR447537 as well as neutralizing anti-drug antibodies (NAbs) against SAR447537.

Investigational products

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

Test 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 16

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 86 files

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

Application history

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