This study has been transitioned to CTIS with ID 2024-513262-19-00 check the CTIS register for the current data. Primary objective:- To evaluate the efficacy of caplacizumab in combination with immunosuppressive therapy (IST) without therapeutic…
ID
Source
Brief title
Condition
- Platelet disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- Proportion of participants achieving Remission without requiring TPE.
Secondary outcome
- Proportion of participants achieving Remission
- Proportion of participants who require TPE
- The occurrence of adverse events (AEs), serious adverse events (SAEs), and
adverse events of special interest (AESIs)
- Proportion of participants achieving Clinical Response
- Time to platelet count response
- Proportion of participants refractory to therapy
- Proportion of participants with TTP-related death
- Proportion of participants with a clinical exacerbation of iTTP
- Proportion of participants with a clinical relapse of iTTP
Background summary
Caplacizumab is currently indicated for the treatment of patients with aTTP
(also known as iTTP), in combination with TPE and IST. Although TPE has been
considered a mainstay of iTTP treatment for several decades, it is a burdensome
and invasive procedure for patients, and is associated with significant
complications, and a substantial number of patients remains at risk for
morbidity and mortality when treated with TPE and immunosuppression alone.
Based on pathophysiology of iTTP and mechanism of action of caplacizumab, it is
hypothesized that caplacizumab and immunosuppression without initial TPE may be
safe and effective as first-line therapy for iTTP. This concept is supported by
pre-clinical data (1) as well as emerging real-world clinical evidence (2).
Hence, the Sponsor is proposing an open-label, single-arm study to support the
hypothesis that caplacizumab and IST can be effectively and safely administered
to treat either first or recurrent iTTP episode in adults without first-line
TPE, which would be added only if clinically indicated. A successful study will
establish a new treatment paradigm and a new standard of care for treatment of
iTTP for the use of caplacizumab and immunosuppression without first-line TPE.
Study objective
This study has been transitioned to CTIS with ID 2024-513262-19-00 check the CTIS register for the current data.
Primary objective:
- 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:
To evaluate:
- the need for therapeutic plasma exchange in adult participants with an
episode of iTTP treated with caplacizumab and IST
- the safety of caplacizumab in combination with IST without 1st line TPE in
adults with iTTP
- the effect of treatment with caplacizumab and IST without 1st line TPE on
clinical response
- the effect of treatment with caplacizumab and IST without 1st line TPE on
restoring platelet counts
- the effect of treatment with caplacizumab and IST without 1st line TPE on
refractory disease
- the effect of treatment with caplacizumab and IST without 1st line TPE on
clinically relevant iTTP-related events consisting of iTTP-related
mortality
- the effect of treatment with caplacizumab and IST without 1st line TPE on
clinically relevant iTTP-related events consisting of exacerbation of
iTTP
- the effect of treatment with caplacizumab and IST without 1st-line TPE on
clinically relevant iTTP-related events consisting of relapse of iTTP
Study design
Adult participants with clinical diagnosis of initial or recurrent iTTP and a
French TMA score of 1 or 2 will be enrolled from sites that are able to obtain
baseline of a disintegrin and metalloproteinase with a thrombospondin type 1
motif13 (ADAMTS13) activity test results within 48 hours. Please see Section 4
and Section 5 for study enrollment criteria and eligibility assessments. After
confirmation of eligibility to study participation, participants will receive
initial treatment consisting of caplacizumab and IST (corticosteroids ±
anti-CD20 antibody [rituximab or biosimilar]) without first-line TPE. However,
participants may start TPE later, if it is determined that there is lack of
adequate response to treatment after the first 24 hours or if there is any
clinical deterioration at any time during the study (please see Section 4.1 for
additional details). It is expected that the participant is hospitalized when
the treatment is started, and the duration of initial hospitalization may vary
based on clinical condition of the individual participant. The
maximum duration allowed for caplacizumab treatment will be 12 weeks for the
presenting episode. The post-treatment follow-up period will be 12 weeks.
In case of clinical exacerbation and clinical relapse, please see Section 4 for
additional details. This study incorporates the revised consensus outcome
definitions for iTTP published by the International Working Group for
thrombotic thrombocytopenic purpura (TTP) that reflect current iTTP management
(3). A Data Monitoring Committee (DMC) will be appointed to monitor the safety
and scientific integrity of this study.
Intervention
Administration of caplacizumab combined with IST, without TPE (standard of care
is inclusive of TPE)
Study burden and risks
The patients follow a lot of the normal procedures when treated for TTP: they
are hospitalized for their condition and will not stay in the hospital longer
than they normally would. The participating PI indicated that day 3 and 4 ECGs
are not normally done and the blood sampling done for central lab evaluation
and PK/PD/ADA/ADAMTS13 antibodies are extra. Most of these punctions are done
together with local lab sampling, which is as per normal follow-up, according
to the PI. This means that no extra needle stick is required to do these
samples.
Risks related to the caplacizumab treatment are as per normal standard of care
treatment, which also includes treatment with caplacizumab.
Paasheuvelweg 25
Amsterdam 1105 BP
NL
Paasheuvelweg 25
Amsterdam 1105 BP
NL
Listed location countries
Age
Inclusion criteria
- 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)
- Participants with a clinical diagnosis of iTTP and a French TMA score of 1 or
2
- 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
- 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
- Platelet count >=100 × 109/L.
- Serum creatinine level >2.26 mg/dL (200 µmol/L) in case platelet count is >30
× 109/L (to exclude possible cases of atypical HUS)
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
- Congenital TTP (known at the time of study entry)
- Clinically significant active bleeding or known co-morbidities associated
with high risk of bleeding (excluding thrombocytopenia)
- Inherited or acquired coagulation disorders
- Malignant arterial hypertension
- Participants requiring or expected to require invasive procedures immediately
(eg, stroke requiring thrombolytic therapy, those who need mechanical
ventilation, etc.)
- Those presenting with severe neurological or severe cardiac disease
- Clinical condition other than that associated with TTP, with life expectancy
<6 months, such as end-stage malignancy.
- 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.
- Participants who were previously enrolled in this clinical study (study
EFC16521)
- 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.
- Positive result on COVID test.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| Other | 2022-001177-31 |
| EU-CTR | CTIS2024-513262-19-00 |
| EudraCT | EUCTR2022-001177-31-NL |
| CCMO | NL81233.100.22 |