Caplacizumab and immunosuppressive therapy without first-line therapeutic plasma exchange in adults with immune-mediated thrombotic thrombocytopenic purpura

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Sanofi-Aventis Recherche & Developpement

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

21 Nov 2022 → 26 Dec 2024

Decision date (initial)

2024-07-22

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2024-513262-19-00

EudraCT number

2022-001177-31

WHO UTN

U1111-1244-0426

ClinicalTrials.gov

NCT05468320

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Pharmacokinetic, Therapy, Pharmacodynamic

To evaluate the efficacy of caplacizumab in combination with immunosuppressive therapy (IST) without therapeutic plasma exchange (TPE) in adults with immune mediated thrombotic thrombocytopenic purpura (iTTP)

Secondary objectives 8

1. To evaluate the need for therapeutic plasma exchange in adult participants with an episode of iTTP treated with caplacizumab and IST.
2. To evaluate the safety of caplacizumab in combination with IST without first-line TPE in adults with iTTP
3. To evaluate the effect of treatment with caplacizumab and IST without first-line TPE on clinical response
4. To evaluate the effect of treatment with caplacizumab and IST without first-line TPE on restoring platelet counts
5. To evaluate the effect of treatment with caplacizumab and IST without first-line TPE on refractory disease
6. To evaluate the effect of treatment with caplacizumab and IST without first-line TPE on clinically relevant iTTP-related events consisting of iTTP-related mortality
7. To evaluate the effect of treatment with caplacizumab and IST without first-line TPE on clinically relevant iTTP-related events consisting of exacerbation of iTTP
8. To evaluate the effect of treatment with caplacizumab and IST without first-line TPE on clinically relevant iTTP-related events consisting of relapse of iTTP

Conditions and MedDRA coding

Thrombotic Thrombocytopenic Purpura

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. -Participants with a clinical diagnosis of iTTP (initial or recurrent), which includes thrombocytopenia, microangiopathic hemolytic anemia (eg, presence of schistocytes in peripheral blood smear) and relatively preserved renal function. The iTTP diagnosis should be confirmed by ADAMTS13 testing within 48 hours (2 days).
2. -Participants with a clinical diagnosis of iTTP and a French TMA score of 1 or 2.
3. -A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies: Is a woman of nonchildbearing potential (WONCBP), OR Is a woman of childbearing potential (WOCBP) and agrees to use an acceptable contraceptive method during the overall treatment period and for at least 2 months after the last study drug administration.
4. -Male participants with female partners of childbearing potential must agree to follow the contraceptive guidance as per protocol during the overall treatment period and for at least 2 months after last study drug administration.

Exclusion criteria 14

1. Participants are excluded from the study if any of the following criteria apply: -Platelet count ≥100x10^9/L.
2. -Serum creatinine level >2.26 mg/dL (200 μmol/L) in case platelet count is > 30x10^9/L (to exclude possible cases of atypical HUS)
3. -Known other causes of thrombocytopenia including but not limited to: • Clinical evidence of enteric infection with E. coli 0157 or related organism • Atypical HUS • Hematopoietic stem cell, bone marrow or solid organ transplantation-associated thrombotic microangiopathy • Known or suspected sepsis • Diagnosis of disseminated intravascular coagulation
4. -Congenital TTP (known at the time of study entry)
5. -Clinically significant active bleeding or known co-morbidities associated with high risk of bleeding (excluding thrombocytopenia)
6. -Inherited or acquired coagulation disorders
7. -Malignant arterial hypertension
8. -Participants requiring or expected to require invasive procedures immediately (eg, stroke requiring thrombolytic therapy, those who need mechanical ventilation, etc.)
9. -Those presenting with severe neurological or cardiac disease
10. -Clinical condition other than that associated with TTP, with life expectancy <6 months, such as end-stage malignancy
11. -Known chronic treatment with anticoagulants and anti-platelet drugs that cannot be stopped (interrupted) safely, including but not limited to: • vitamin K antagonists • direct-acting oral anticoagulants • heparin or low molecular weight heparin (LMWH) • non-steroidal anti-inflammatory molecules other than acetyl salicylic acid
12. -Participants who were previously enrolled in this clinical study (study EFC16521).
13. -Participants who received an investigational drug, or device, other than caplacizumab, within 30 days of anticipated IMP administration or 5 half-lives of the previous investigational drug, whichever is longer.
14. -Positive result on COVID test.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Proportion of participants achieving Remission without requiring therapeutic plasma exchange (TPE).

Secondary endpoints 13

1. Proportion of participants achieving Remission
2. Proportion of participants who require TPE
3. The occurrence of adverse events (AEs), serious adverse events (SAEs), and adverse events of special interest (AESIs)
4. Proportion of participants achieving Clinical Response (On-treatment period from day 1 to day 84)
5. Proportion of participants achieving Clinical Response (Overall study period from day 1 to day 168)
6. Time to platelet count response
7. Proportion of participants refractory to therapy
8. Proportion of participants with TTP-related death (On-treatment period from day 1 to day 84)
9. Proportion of participants with TTP-related death (Overall study period from day 1 to day 168)
10. Proportion of participants with a clinical exacerbation of iTTP (On-treatment period from day 1 to day 84)
11. Proportion of participants with a clinical exacerbation of iTTP (Overall study period from day 1 to day 168)
12. Proportion of participants with a clinical relapse of iTTP (On-treatment period from day 1 to day 84)
13. Proportion of participants with a clinical relapse of iTTP (Overall study period from day 1 to day 168)

Investigational products

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

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Sanofi-Aventis Recherche & Developpement

Sponsor organisation

Sanofi-Aventis Recherche & Developpement

Address

1 Avenue Pierre Brossolette

City

Chilly-Mazarin

Postcode

91380

Country

France

Scientific contact point

Organisation

Sanofi-Aventis Recherche & Developpement

Contact name

Clinical Sciences and Operations

Public contact point

Organisation

Sanofi-Aventis Recherche & Developpement

Contact name

Clinical Sciences and Operations

Third parties 7

Locations

9 EU/EEA countries · 30 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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 12 files

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

Application history

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