Purpura, Thrombotic ThrombocytopenicPhase 2NCT02854059

IdeS in Asymptomatic Antibody-Mediated Thrombotic Thrombocytopenic Purpura (TTP) Patients

A Phase 2 study testing IdeS (0.25 mg/kg) and IdeS (0.50 mg/kg) in people with Purpura, Thrombotic Thrombocytopenic, run by Hansa Biopharma AB at 1 site in United Kingdom.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

The main purpose of this study is to evaluate safety and tolerability in patients diagnosed with asymptomatic antibody-mediated TTP with low ADAMTS13 activity after receiving single intravenous dose of IdeS. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Purpura, Thrombotic Thrombocytopenic
What is being tested?: IdeS (0.25 mg/kg) and IdeS (0.50 mg/kg)
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 2 participants
Where: 1 siteUnited Kingdom
Study dates: Sep 2016to Jan 2017
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Age 18 years or above
Diagnosed with acquired TTP with ADAMTS13 levels of ≤ 10 % in clinical remission and with measurable or previously confirmed ADAMTS13 antibodies

Who cannot join

Prior malignancy within 5 years
Test positive for serum hepatitis B surface antigen, hepatitis C antibody and human immunodeficiency virus (HIV)
Ongoing infectious disease including P-CRP >10
Test positive for IgE antibodies against IdeS
Secondary cause of TTP
Rituximab treatment or other antibody-based therapy within 7 days prior to IdeS dosing

Show all 14Show fewer

Treatment with investigational medicinal product within the last 12 weeks proceeding screening
Severe other conditions requiring treatment and close monitoring, e.g. cardiac failure > NYHA (New York Heart Association) grade 3, unstable coronary disease or oxygen dependent COPD
History of any other clinically significant disease or disorder which may either put the patient at increased risk because of participation in the study, or influence the results or the patient's ability to participate in the study
Hypogammaglobulinemia defined as any values of P-total IgG less than 3 g/L
History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, or history of hypersensitivity to drugs with a similar chemical structure or class to IdeS (e. g. streptokinase and/or staphylokinase)
Substance abuse or other concurrent medical condition that could confound study interpretation or affect the patient's ability to tolerate or complete the study
Breast feeding women or women with a positive pregnancy test
Previously received IdeS treatment

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

University College London Hospitals NHS
London, Greater London, NW1 2PG

Other trials in United Kingdom

About this study

Official title: A Phase II Pilot Study to Evaluate the Safety, Tolerability, Efficacy, Pharmacodynamics and Pharmacokinetics of IdeS in Asymptomatic Antibody-Mediated Thrombotic Thrombocytopenic Purpura (TTP) Patients With Low ADAMTS13 Activity

Read the detailed description

Immunoglobulin G-degrading enzyme of Streptococcus pyogenes (IdeS) is an IgG specific endopeptidase which cleaves IgG molecules and efficiently neutralizes Fc-mediated activities. IdeS-mediated IgG degradation constitutes a novel therapeutic principle for the treatment of IgG-driven human diseases.

In addition to assessing the safety and tolerability of IdeS the study will also assess the efficacy of IdeS to significantly increase the ADAMTS13 activity and decrease the anti-ADAMTS13 antibody levels in patients diagnosed with asymptomatic antibody-mediated TTP with low ADAMTS13 activity.

Conditions: Purpura, Thrombotic Thrombocytopenic
Being tested: IdeS (0.25 mg/kg), IdeS (0.50 mg/kg)
Keywords: Asymptomatic antibody-mediated TTP
Medical subject headings: Purpura, Thrombotic Thrombocytopenic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

IdeS (0.25 mg/kg)Biological
Also called HMed-IdeS, IgG-degrading enzyme of Streptococcus pyogenes
Single i.v. infusion of IdeS (0.25 mg/kg). Following an evaluation of efficacy and safety in the first 3 patients the dose may be increased in the following 3 patients to 0.5 mg/kg.
IdeS (0.50 mg/kg)Biological
Also called HMed-IdeS, IgG-degrading enzyme of Streptococcus pyogenes
Single i.v. infusion of IdeS (0.50 mg/kg).

Study groups in NCT02854059
Study group	Role	What they receive
Treatment IdeS (0.25 mg/kg)	Experimental	A single 30 minutes i.v. infusion of IdeS (0.25 mg/kg). Following an evaluation of safety and efficacy in 3 patients receiving 0.25 mg/kg there will be a potential to increase the IdeS dose to 0.5 mg/kg for the remaining 3 patients. Receives: Biological: IdeS (0.25 mg/kg)
Treatment IdeS (0.50 mg/kg)	Experimental	A single 30 minutes i.v. infusion of IdeS (0.50 mg/kg). Receives: Biological: IdeS (0.50 mg/kg)

What is being measured

The primary outcome is the main question the study is designed to answer.

Safety and Tolerability as Measured by Type, Frequency and Intensity of Adverse Events
Data on AEs were obtained if spontaneously reported by the patient, if reported in response to an open question from the study personnel or if revealed by observation.
A treatment emergent AE (TEAE) is defined as any AE occurring after administration of the IMP and within the time of the residual drug effect period (i.e. 30 days after IMP administration).
AEs reported in ClinicalTrials.gov include TEAEs and post-treatment AEs, i.e. all AEs occurring after administration of IdeS until end of study.
Please refer to Adverse Event section for details on reported AEs
Measured: From dosing until end of follow up on day 64

Secondary outcomes (8)

Number of Patients With Change From Baseline in ADAMTS13 Activity
ADAMTS13 is an enzyme which is inhibited in patients with TTP. The efficacy of IdeS on ADAMTS13 activity was measured througout the study as change from baseline.
Measured: From day of dosing until end of follow up on day 64
Number of Patients With Change From Baseline in ADAMTS13 Antibody Levels
The efficacy of IdeS on ADAMTS13 antibody cleaving was measured througout the study as change from baseline in ADAMTS13 antibody concentration.
Measured: From day of dosing until end of follow up on day 64
Number of Patients for Whom a Decreased ADAMTS13 Activity Returned to Normal Levels at Different Time-points in the Study
The ADAMTS13 activity in TTP patients is decreased. The efficacy of IdeS on ADAMTS13 activity was assessed throughout the study to identify the time-point of return to normal levels.
Measured: From day of dosing until end of follow up on day 64
Number of Patients With Change From Baseline in Pharmacodynamics as Measured by Level of IgG
IdeS cleaves IgG molecules. The concentration of uncleaved IgG in the patient's serum was measured throughout the study to determine change from baseline following IdeS administration.
Measured: From day of dosing until end of follow up on day 64
Number of Patients Showing IdeS Immunogenicity as Measured by Anti-drug Antibodies
Most humans have been infected with S. pyogenes which is the origin of IdeS. It was therefore expected that patients in this study might have antibodies against IdeS before being exposed to IdeS in the study. The concentration of ant-IdeS antibodies was measured before dosing and throughout the study.
Measured: From day of dosing until end of follow up on day 64
Maximum Serum Concentration (Cmax) of IdeS
The concentration of IdeS in serum was measured to identify the pharmacokinetic parameter Cmax of IdeS in TTP patients.
Measured: From day of dosing until day 14
Time-point for Maximum Serum Concentration of IdeS
The concentration of IdeS in serum was measured to identify the pharmacokinetic parameter Tmax of IdeS in TTP patients. Tmax refers to the time-point when the serum concentration of IdeS reaches maximum.
Measured: From day of dosing until day 14
Number of Patients With Change From Baseline in Pharmacodynamics as Measured by Level of F(ab')2 Fragments
The efficacy of IdeS can be measured as change from baseline in F(ab')2 fragments (i.e. the antigen binding fragment of IgG).
Measured: From day of dosing until end of follow up on day 64

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Sep 2016Jan 2017

First posted3 Aug 2016 (estimated)
Study startSep 2016
Primary completionJan 2017
Study completionJan 2017

Why it stopped: Sponsor review of initial results demonstrates a non-favourable risk benefit

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Purpura, Thrombotic ThrombocytopenicStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Enrolment: 2 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02854059
Sponsor's protocol ID: 15-HMedIdeS-08
Status last verified: Sep 2019
First submitted: 27 Jul 2016
Last updated: 13 Sep 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
Individual data sharing: No: An internal monitoring committee (IMC) at the sponsor will review available safety and tolerability data after 3 patients have received a dose of 0.25 mg/kg before proceeding to the next dose (0.5 mg/kg). Safety data collected up to and including day 14 will be evaluated.

Publications

Stubbs MJ, Thomas M, Vendramin C, Sonesson E, Kjellman C, Jarnum S, Stenberg Y, Elfving C, Scully M. Administration of immunoglobulin G-degrading enzyme of Streptococcus pyogenes (IdeS) for persistent anti-ADAMTS13 antibodies in patients with thrombotic thrombocytopenic purpura in clinical remission. Br J Haematol. 2019 Jul;186(1):137-140. doi: 10.1111/bjh.15706. Epub 2018 Nov 29. No abstract available.
PubMed 30488420

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingObservational study
A Study in Children and, Adults With Congenital Thrombotic Thrombocytopenic Purpura (cTTP) Treated With Adzynma
Thrombotic Thrombocytopenic Purpura (TTP)
RecruitingPhase 2
A Study to Assess the Tolerability of Ianalumab (VAY736) With Investigator's Choice Thrombopoietin Receptor Agonist (IC TPO-RA) in Patients With Primary Immune Thrombocytopenia (ITP)
Primary Immune Thrombocytopenia (ITP), Primary Evans Syndrome (ES)
RecruitingPhase 1/2
A Study of Pirtobrutinib in Participants With Immune Thrombocytopenia
Immune Thrombocytopenia (ITP)
RecruitingPhase 3
A Study of Mezagitamab in Adults With Chronic Primary Immune Thrombocytopenia
Immune Thrombocytopenic Purpura (ITP)
RecruitingPhase 2
Study to Assess the Safety and Tolerability of Tafasitamab in Adult Participants With Primary Autoimmune Blood Cell Disorders
Immune Thrombocytopenia

All Purpura, Thrombotic Thrombocytopenic trials

Study at a glance

From the registry record, last updated by the sponsor on 13 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase II Pilot Study to Evaluate the Safety, Tolerability, Efficacy, Pharmacodynamics and Pharmacokinetics of IdeS in Asymptomatic Antibody-Mediated Thrombotic Thrombocytopenic Purpura (TTP) Patients With Low ADAMTS13 Activity
ClinicalTrials.gov ID: NCT02854059
Acronym / sponsor ID: 15-HMedIdeS-08
Conditions: Purpura, Thrombotic Thrombocytopenic
Keywords: Asymptomatic antibody-mediated TTP
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: Sponsor review of initial results demonstrates a non-favourable risk benefit
Enrolment: 2 participants (actual)
Lead sponsor: Hansa Biopharma ABIndustry (pharma, biotech, devices)
Collaborators: University College London Hospitals
Study start: Sep 2016
Primary completion: Jan 2017 (actual)
Study completion: Jan 2017 (actual)
First posted: 3 Aug 2016 (estimated)
Results: Posted 13 Sep 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Treatment IdeS (0.25 mg/kg)	Experimental	Biological: IdeS (0.25 mg/kg)A single 30 minutes i.v. infusion of IdeS (0.25 mg/kg). Following an evaluation of safety and efficacy in 3 patients receiving 0.25 mg/kg there will be a potential to increase the IdeS dose to 0.5 mg/kg for the remaining 3 patients.
Treatment IdeS (0.50 mg/kg)	Experimental	Biological: IdeS (0.50 mg/kg)A single 30 minutes i.v. infusion of IdeS (0.50 mg/kg).

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (2 listed)

Age 18 years or above
Diagnosed with acquired TTP with ADAMTS13 levels of ≤ 10 % in clinical remission and with measurable or previously confirmed ADAMTS13 antibodies

Key exclusion criteria (14 listed)

Prior malignancy within 5 years
Test positive for serum hepatitis B surface antigen, hepatitis C antibody and human immunodeficiency virus (HIV)
Ongoing infectious disease including P-CRP >10
Test positive for IgE antibodies against IdeS
Secondary cause of TTP

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
IdeS (0.25 mg/kg)Also: HMed-IdeS, IgG-degrading enzyme of Streptococcus pyogenesSingle i.v. infusion of IdeS (0.25 mg/kg). Following an evaluation of efficacy and safety in the first 3 patients the dose may be increased in the following 3 patients to 0.5 mg/kg.	Biological	Treatment IdeS (0.25 mg/kg)
IdeS (0.50 mg/kg)Also: HMed-IdeS, IgG-degrading enzyme of Streptococcus pyogenesSingle i.v. infusion of IdeS (0.50 mg/kg).	Biological	Treatment IdeS (0.50 mg/kg)

Primary outcome

Safety and Tolerability as Measured by Type, Frequency and Intensity of Adverse Events
Time frame: From dosing until end of follow up on day 64
Data on AEs were obtained if spontaneously reported by the patient, if reported in response to an open question from the study personnel or if revealed by observation. A treatment emergent AE (TEAE) is defined as any AE occurring after administration of the IMP and within the time of the residual drug effect period (i.e. 30 days after IMP administration). AEs reported in ClinicalTrials.gov include TEAEs and post-treatment AEs, i.e. all AEs occurring after administration of IdeS until end of study. Please refer to Adverse Event section for details on reported AEs

8 secondary outcomes

Number of Patients With Change From Baseline in ADAMTS13 Activity
Time frame: From day of dosing until end of follow up on day 64
Number of Patients With Change From Baseline in ADAMTS13 Antibody Levels
Time frame: From day of dosing until end of follow up on day 64
Number of Patients for Whom a Decreased ADAMTS13 Activity Returned to Normal Levels at Different Time-points in the Study
Time frame: From day of dosing until end of follow up on day 64
Number of Patients With Change From Baseline in Pharmacodynamics as Measured by Level of IgG
Time frame: From day of dosing until end of follow up on day 64
Number of Patients Showing IdeS Immunogenicity as Measured by Anti-drug Antibodies
Time frame: From day of dosing until end of follow up on day 64
Maximum Serum Concentration (Cmax) of IdeS
Time frame: From day of dosing until day 14
Time-point for Maximum Serum Concentration of IdeS
Time frame: From day of dosing until day 14
Number of Patients With Change From Baseline in Pharmacodynamics as Measured by Level of F(ab')2 Fragments
Time frame: From day of dosing until end of follow up on day 64

Results and safety

Results posted to the registry on 13 Sep 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Treatment IdeS (0.25 mg/kg)	2	2
IdeS (0.50 mg/kg)	0	0

Primary outcome: Safety and Tolerability as Measured by Type, Frequency and Intensity of Adverse Events

Time frame: From dosing until end of follow up on day 64. Number. Unit: Adverse Events

Measure	Treatment IdeS (0.25 mg/kg) n = 2	Treatment IdeS (0.50 mg/kg) n = 0
TEAEs	10	–
Mild TEAEs (Grade=1)	7	–
Moderate TEAEs (Grade=2)	1	–
Severe TEAEs (Grade=3)	1	–
Life threatening TEAEs (Grade=4)	1	–
Related TEAEs	4	–
Serious TEAEs	2	–
Post-TEAEs	2	–

Population analysed: Because of the premature termination of the study due to the non-favourable risk-benefit profile in the first 2 patients and since the sponsor will no longer pursue the indication, the analyses as described in the protocol were not performed. Instead, data collected for the 2 enrolled subjects were listed and/or presented graphically.

8 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse events (AEs) were collected for a time-period of 3 months for the individual subject (i.e. from the subject signed the informed consent form (ICF) throughout the study including the follow-up period until the end of study visit).. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Treatment IdeS (0.25 mg/kg)	2 of 2 (100%)	2 of 2 (100%)	0 of 2
Treatment IdeS (0.50 mg/kg)	0 of 0	0 of 0	0

Limitations and caveats (from the sponsor): Early termination leading to small number of subjects analyzed.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 13 Sep 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 30488420Stubbs MJ, Thomas M, Vendramin C, Sonesson E, Kjellman C, Jarnum S, Stenberg Y, Elfving C, Scully M. Administration of immunoglobulin G-degrading enzyme of Streptococcus pyogenes (IdeS) for persistent anti-ADAMTS13 antibodies in patients with thrombotic thrombocytopenic purpura in clinical remission. Br J Haematol. 2019 Jul;186(1):137-140. doi: 10.1111/bjh.15706. Epub 2018 Nov 29. No abstract available.
Individual participant dataSharing planned: No. An internal monitoring committee (IMC) at the sponsor will review available safety and tolerability data after 3 patients have received a dose of 0.25 mg/kg before proceeding to the next dose (0.5 mg/kg). Safety data collected up to and including day 14 will be evaluated.

Related trials for Purpura, Thrombotic Thrombocytopenic

RecruitingObservational study
A Study in Children and, Adults With Congenital Thrombotic Thrombocytopenic Purpura (cTTP) Treated With Adzynma
Thrombotic Thrombocytopenic Purpura (TTP)
RecruitingPhase 2
A Study to Assess the Tolerability of Ianalumab (VAY736) With Investigator's Choice Thrombopoietin Receptor Agonist (IC TPO-RA) in Patients With Primary Immune Thrombocytopenia (ITP)
Primary Immune Thrombocytopenia (ITP), Primary Evans Syndrome (ES)
RecruitingPhase 1/2
A Study of Pirtobrutinib in Participants With Immune Thrombocytopenia
Immune Thrombocytopenia (ITP)
RecruitingPhase 3
A Study of Mezagitamab in Adults With Chronic Primary Immune Thrombocytopenia
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RecruitingPhase 2
Study to Assess the Safety and Tolerability of Tafasitamab in Adult Participants With Primary Autoimmune Blood Cell Disorders
Immune Thrombocytopenia

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Elisabeth Sonesson, PhD study director

Hansa Biopharma AB

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing IdeS (0.25 mg/kg) and IdeS (0.50 mg/kg) in people with Purpura, Thrombotic Thrombocytopenic, run by Hansa Biopharma AB at 1 site in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 13 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 13 Sep 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety and Tolerability as Measured by Type, Frequency and Intensity of Adverse Events (time frame: From dosing until end of follow up on day 64). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02854059, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Sep 2019.