Long-Term Tolerability and Safety of HYQVIA/HyQvia in CIDP

Study at a glance

From the registry record, last updated by the sponsor on 28 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title

Long-Term Tolerability and Safety of Immune Globulin Infusion 10% (Human) With Recombinant Human Hyaluronidase (HYQVIA/HyQvia) for the Treatment of Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP)

ClinicalTrials.gov ID

NCT02955355

Acronym / sponsor ID

161505

Conditions

Chronic Inflammatory Demyelinating Polyradiculoneuropathy

Phase

Phase 3

Study type

Interventional

Recruitment status

Completed

Enrolment

85 participants (actual)

Lead sponsor

Baxalta now part of ShireIndustry (pharma, biotech, devices)

Collaborators

Takeda Development Center Americas, Inc.

Study start

14 Nov 2016 (actual)

Primary completion

4 Jul 2023 (actual)

Study completion

4 Jul 2023 (actual)

First posted

4 Nov 2016 (estimated)

Results

Posted 28 Aug 2024

Clinical summary

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

Study design

Primary purpose

Treatment

Allocation

Not applicable

Intervention model

Single group

Masking

None (open label)

Number of arms

1

Who may qualify

Ages

18 years and older

Sex

All

Healthy volunteers

Not accepted

Age groups

Adult, Older adult

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

Interventions

Primary outcome

1. Number of Participants With Any Treatment-emergent Serious Adverse Events (SAEs) and Adverse Events (AEs), Regardless of Causality

   Time frame: From the first dose of study drug up to end of study (up to 6.6 years)

   An AE was defined as any untoward medical occurrence in a participant administered an investigational product (IP) that did not necessarily have a causal relationship with the treatment. An SAE was defined as an untoward medical occurrence that at any dose met one or more of the following criteria: outcome was fatal/resulted in death, was life-threatening, required inpatient hospitalization or resulted in prolongation of an existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. Treatment emergent adverse events (TEAEs) were defined as adverse events that occurred during or after administration of the first dose of IP in this Extension Study.

2. Number of Participants With Causally Related Treatment-emergent SAEs and AEs

   Time frame: From the first dose of study drug up to end of study (up to 6.6 years)

   An AE was defined as any untoward medical occurrence in a participant administered an IP that did not necessarily have a causal relationship with the treatment. An SAE was defined as an untoward medical occurrence that at any dose met one or more of the following criteria: outcome was fatal/resulted in death, was life-threatening, required inpatient hospitalization or resulted in prolongation of an existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. TEAEs were defined as adverse events that occurred during or after administration of the first dose of IP in this Extension Study. Causality was used to determine whether there was a reasonable possibility that the IP was etiologically related to/associated with the AE.

3. Number of Participants With Adverse Reactions (ARs) or Suspected Adverse Reactions (SARs) Categorized as Serious and Non-serious

   Time frame: From the first dose of study drug up to end of study (up to 6.6 years)

   An AR plus SAR is any AE that meets any of the following criteria: an AE considered by either the investigator and/or the sponsor to be possibly or probably related to IP administration, or that begins during infusion of IP or within 72 hours following the end of IP infusion, or AE for which causality assessment is missing or indeterminate. Serious AR/SAR=any AR/SAR that is an untoward medical occurrence which at any dose meets one or more of following criteria: outcome is fatal/results in death, is life-threatening, requires inpatient hospitalization or results in prolongation of existing hospitalization, results in persistent or significant disability/incapacity,is a congenital anomaly/birth defect,is a medically important event,thromboembolic events,hemolytic anemia. Nonserious AR/SAR=AR/SAR that does not meet the criteria.

4. Percentage of Participants With Treatment-Emergent Adverse Events That May be a Result of Immune-Mediated Responses

   Time frame: From the first dose of study drug up to end of study (up to 6.6 years)

   Percentage of participants with TEAEs that may be a result of immune-mediated response to either immunoglobulin, rHuPH20, or other factors such as allergic reactions, immune complex-mediated reactions: local, complex-mediated reactions: systemic, thrombotic and embolic events were assessed. TEAEs were defined as adverse events that occurred during or after administration of the first dose of IP in this Extension Study. The percentage was rounded off to the nearest decimal.

5. Number of Treatment-Emergent SAEs and AEs Associated With Infusions, Regardless of Causality

   Time frame: From the first dose of study drug up to end of study (up to 6.6 years)

   An AE was defined as any untoward medical occurrence in a participant administered an IP that did not necessarily have a causal relationship with the treatment. An SAE was defined as an untoward medical occurrence that at any dose met one or more of the following criteria: outcome was fatal/resulted in death, was life-threatening, required inpatient hospitalization or resulted in prolongation of an existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. TEAEs were defined as adverse events that occurred during or after administration of the first dose of IP in this Extension Study. AEs associated with an infusion are defined as AEs occurring after administration of IP (or any TEAE). Participants can have more than one TEAE associated with infusion.

6. Number of Causally Related Treatment-Emergent SAEs and AEs Associated With Infusions

   Time frame: From the first dose of study drug up to end of study (up to 6.6 years)

   An AE was defined as any untoward medical occurrence in a participant administered an IP that did not necessarily have a causal relationship with the treatment. An SAE was defined as an untoward medical occurrence that at any dose met one or more of the following criteria: outcome was fatal/resulted in death, was life-threatening, required inpatient hospitalization or resulted in prolongation of an existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. TEAEs were defined as adverse events that occurred during or after administration of the first dose of IP in this Extension Study. AEs associated with an infusion are defined as AEs occurring after administration of IP (or any TEAE). Causality was used to determine whether there was a reasonable possibility that the IP was etiologically related to/associated with the AE.

7. Number of TEAEs Temporally Associated With Infusions

   Time frame: From the first dose of study drug up to end of study (up to 6.6 years)

   TEAEs that occurred during infusion or within 72 hours post-infusion were considered to be temporally associated with infusions. TEAEs were defined as adverse events that occurred during or after administration of the first dose of IP in this Extension Study. Participants can have more than one TEAE temporally associated with infusion.

8. Number of Serious and Non-Serious ARs or SARs Associated With Infusions

   Time frame: From the first dose of study drug up to end of study (up to 6.6 years)

   An AR/SAR=any AE that meets any of following criteria: AE considered by either investigator and/or sponsor to be possibly or probably related to IP administration, begins during infusion of IP or within 72 hours following end of IP infusion,or AE for which causality assessment is missing or indeterminate. ARs/SARs associated with an infusion=AEs considered by the investigator to be occurring after administration of IP. Serious AR/SAR=any AR/SAR that is an untoward medical occurrence which at any dose meets one or more of following criteria: outcome is fatal/results in death, is life-threatening, requires inpatient hospitalization or results in prolongation of existing hospitalization, results in persistent or significant disability/incapacity,is a congenital anomaly/birth defect,is a medically important event,thromboembolic events,hemolytic anemia. Nonserious AR/SAR=AR/SAR that does not meet the criteria. Participants can have more than one AR/SAR associated with infusion.

9. Number of Infusions Associated With One or More Systemic TEAEs

   Time frame: From the first dose of study drug up to end of study (up to 6.6 years)

   An AE was defined as any untoward medical occurrence in a participant administered an IP that did not necessarily have a causal relationship with the treatment. TEAEs were defined as adverse events that occurred during or after administration of the first dose of IP in this Extension Study. Systemic TEAEs were defined as AEs that were not included in the Medical Dictionary for Regulatory Activities (MedDRA) Higher Level Group Term "administration site reactions" and did not contain the phrase "injection site". Infusions associated with one or more AEs are defined as follows: if an AE occurs after an infusion but prior to the next infusion that infusion is associated with that AE.

10. Number of Infusions Associated With One or More Local TEAEs

    Time frame: From the first dose of study drug up to end of study (up to 6.6 years)

    An AE was defined as any untoward medical occurrence in a participant administered an IP that did not necessarily have a causal relationship with the treatment. TEAEs were defined as adverse events that occurred during or after administration of the first dose of IP in this Extension Study. Local TEAEs were defined as AEs that were included in the MedDRA Higher Level Group Term "administration site reactions" or contained the phrase "injection site" or "infection site". Infusions associated with one or more AEs are defined as follows: if an AE occurs after an infusion but prior to the next infusion that infusion is associated with that AE.

11. Number of Infusions for Which the Infusion Rate Was Reduced and/or the Infusion Was Interrupted or Stopped Due to Intolerability and/or TEAEs

    Time frame: From the first dose of study drug up to end of study (up to 6.6 years)

    An AE was defined as any untoward medical occurrence in a participant administered an IP that did not necessarily have a causal relationship with the treatment. TEAEs were defined as adverse events that occurred during or after administration of the first dose of IP in this Extension Study.

12. Rate of TEAEs Categorized as Systemic and Local Regardless of Causality, Expressed as Number of Events Per Infusion

    Time frame: From the first dose of study drug up to end of study (up to 6.6 years)

    TEAEs were defined as adverse events that occurred during or after administration of the first dose of IP in this Extension Study. Systemic TEAEs were defined as AEs that were not included in the MedDRA Higher Level Group Term "administration site reactions" and did not contain the phrase "injection site". Local TEAEs were defined as AEs that were included in the MedDRA Higher Level Group Term "administration site reactions" or contained the phrase "injection site" or "infection site". Data for number of events per infusion was assessed at the group level calculated by dividing number of events by total number of infusions administered to participants in the Safety Analysis Set.

13. Rate of TEAEs Categorized as Systemic and Local Regardless of Causality, Expressed as Number of Events Per Participant

    Time frame: From the first dose of study drug up to end of study (up to 6.6 years)

    TEAEs were defined as adverse events that occurred during or after administration of the first dose of IP in this Extension Study. Systemic TEAEs were defined as AEs that were not included in the MedDRA Higher Level Group Term "administration site reactions" and did not contain the phrase "injection site". Local TEAEs were defined as AEs that were included in the MedDRA Higher Level Group Term "administration site reactions" or contained the phrase "injection site" or "infection site". Data for number of events per participant was assessed at the group level calculated by dividing number of events by total number of participants in the Safety Analysis Set.

14. Rate of TEAEs Categorized as Systemic and Local Regardless of Causality, Expressed as Number of Events Per 1000 Participant-year

    Time frame: From the first dose of study drug up to end of study (up to 6.6 years)

    TEAEs were defined as adverse events that occurred during or after administration of the first dose of IP in this Extension Study. Systemic TEAEs were defined as AEs that were not included in the MedDRA Higher Level Group Term "administration site reactions" and did not contain the phrase "injection site". Local TEAEs were defined as AEs that were included in the MedDRA Higher Level Group Term "administration site reactions" or contained the phrase "injection site" or "infection site". Events per participant-years was calculated as follows: 1000 x (number of events / total number of days of exposure, i.e., the sum of duration of treatment for all participants in the Safety Analysis Set, divided by 365.25).

15. Rate of IP-Related TEAEs Categorized as Systemic and Local, Expressed as Number of Events Per Infusion

    Time frame: From the first dose of study drug up to end of study (up to 6.6 years)

    TEAEs were defined as adverse events that occurred during or after administration of the first dose of IP in this Extension Study. Systemic TEAEs were defined as AEs that were not included in the MedDRA Higher Level Group Term "administration site reactions" and did not contain the phrase "injection site". Local TEAEs were defined as AEs that were included in the MedDRA Higher Level Group Term "administration site reactions" or contained the phrase "injection site" or "infection site". An adverse event that was "possibly related" or "probably related" to IP, or for which the relationship was unknown or missing, was considered as a "related AE". Data for number of events per infusion was assessed at the group level calculated by dividing number of events by total number of infusions administered to participants in the Safety Analysis Set.

16. Rate of IP-Related TEAEs Categorized as Systemic and Local, Expressed as Number of Events Per Participant

    Time frame: From the first dose of study drug up to end of study (up to 6.6 years)

    TEAEs were defined as adverse events that occurred during or after administration of the first dose of IP in this Extension Study. Systemic TEAEs were defined as AEs that were not included in the MedDRA Higher Level Group Term "administration site reactions" and did not contain the phrase "injection site". Local TEAEs were defined as AEs that were included in the MedDRA Higher Level Group Term "administration site reactions" or contained the phrase "injection site" or "infection site". An adverse event that was "possibly related" or "probably related" to IP, or for which the relationship was unknown or missing, was considered as a "related AE". Data for number of events per participant was assessed at the group level calculated by dividing number of events by total number of participants in the Safety Analysis Set.

17. Rate of IP-Related TEAEs Categorized as Systemic and Local, Expressed as Number of Events Per 1000 Participant-year

    Time frame: From the first dose of study drug up to end of study (up to 6.6 years)

    TEAEs were defined as adverse events that occurred during or after administration of the first dose of IP in this Extension Study. Systemic TEAEs were defined as AEs that were not included in the MedDRA Higher Level Group Term "administration site reactions" and did not contain the phrase "injection site". Local TEAEs were defined as AEs that were included in the MedDRA Higher Level Group Term "administration site reactions" or contained the phrase "injection site" or "infection site". An adverse event that was "possibly related" or "probably related" to IP, or for which the relationship was unknown or missing, was considered as a "related AE". Events per participant-years was calculated as follows: 1000 x (number of events / total number of days of exposure, i.e., the sum of duration of treatment for all participants in the Safety Analysis Set, divided by 365.25).

18. Rate of ARs or SARs Categorized as Local and Systemic, Expressed as Reactions Per Infusion

    Time frame: From the first dose of study drug up to end of study (up to 6.6 years)

    An AR plus SAR is any AE that meets any of the following criteria: an AE considered by either the investigator and/or the sponsor to be possibly or probably related to IP administration, or that begins during infusion of IP or within 72 hours following the end of IP infusion, or AE for which causality assessment is missing or indeterminate. Systemic AEs were defined as AEs that were not included in the MedDRA Higher Level Group Term "administration site reactions" and did not contain the phrase "injection site". Local AEs were defined as AEs that were included in the MedDRA Higher Level Group Term "administration site reactions" or contained the phrase "injection site" or "infection site". Data for number of events per infusion was assessed at the group level calculated by dividing number of events by total number of infusions administered to participants in the Safety Analysis Set.

19. Rate of ARs or SARs Categorized as Local and Systemic, Expressed as Reactions Per Participant

    Time frame: From the first dose of study drug up to end of study (up to 6.6 years)

    An AR plus SAR is any AE that meets any of the following criteria: an AE considered by either the investigator and/or the sponsor to be possibly or probably related to IP administration, or that begins during infusion of IP or within 72 hours following the end of IP infusion, or AE for which causality assessment is missing or indeterminate. Systemic AEs were defined as AEs that were not included in the MedDRA Higher Level Group Term "administration site reactions" and did not contain the phrase "injection site". Local AEs were defined as AEs that were included in the MedDRA Higher Level Group Term "administration site reactions" or contained the phrase "injection site" or "infection site". Data for number of events per participant was assessed at the group level calculated by dividing number of events by total number of participants in the Safety Analysis Set.

20. Rate of ARs or SARs Categorized as Local and Systemic, Expressed as Reactions Per 1000 Participant-year

    Time frame: From the first dose of study drug up to end of study (up to 6.6 years)

    An AR plus SAR is any AE that meets any of the following criteria: an AE considered by either the investigator and/or the sponsor to be possibly or probably related to IP administration, or that begins during infusion of IP or within 72 hours following the end of IP infusion, or AE for which causality assessment is missing or indeterminate. Systemic AEs were defined as AEs that were not included in the MedDRA Higher Level Group Term "administration site reactions" and did not contain the phrase "injection site". Local AEs were defined as AEs that were included in the MedDRA Higher Level Group Term "administration site reactions" or contained the phrase "injection site" or "infection site". Events per participant-years was calculated as follows: 1000 x (number of events / total number of days of exposure, i.e., the sum of duration of treatment for all participants in the Safety Analysis Set, divided by 365.25).

21. Number of Participants With a TEAE That Led to Discontinuation From Study

    Time frame: From the first dose of study drug up to end of study (up to 6.6 years)

    An AE was defined as any untoward medical occurrence in a participant administered an IP that did not necessarily have a causal relationship with the treatment. TEAEs were defined as adverse events that occurred during or after administration of the first dose of IP in this Extension Study.

22. Number of Participants With Moderate or Severe TEAEs That May be a Result of Immune-Mediated Responses

    Time frame: From the first dose of study drug up to end of study (up to 6.6 years)

    An AE was defined as any untoward medical occurrence in a participant administered an IP that did not necessarily have a causal relationship with the treatment. TEAEs were defined as adverse events that occurred during or after administration of the first dose of IP in this Extension Study. A moderate or severe AE could be a result of immune-mediated response to either immunoglobulin, rHuPH20, or other factors such as allergic reactions, immune complex-mediated reactions: local, complex-mediated reactions: systemic, thrombotic and embolic events. The severity of each AE was assessed by the investigator using clinical expertise based on the following description: moderate=AE produces limited impairment of function and may require therapeutic intervention and produces no sequela/sequelae; severe=AE results in a marked impairment of function and may lead to temporary inability to resume usual life pattern and produces sequela/sequelae, which require (prolonged) therapeutic intervention.

23. Rate of Moderate or Severe TEAEs That May be a Result of Immune-Mediated Responses, Expressed as Number of Events Per 100 Infusions

    Time frame: From the first dose of study drug up to end of study (up to 6.6 years)

    An AE was defined as any untoward medical occurrence in a participant administered an IP that did not necessarily have a causal relationship with the treatment. TEAEs were defined as adverse events that occurred during or after administration of the first dose of IP in this Extension Study. A moderate or severe AE could be a result of immune-mediated response to either immunoglobulin, rHuPH20, or other concomitant medications. The severity of each AE was assessed by the investigator using clinical expertise. Data for number of events per 100 infusions was assessed at the group level calculated by dividing number of events by total number of infusions and multiplying that by 100.

24. Number of Participants That Experienced Treatment-Emergent Local Infusion Site Reactions

    Time frame: From the first dose of study drug up to end of study (up to 6.6 years)

    TEAEs were defined as adverse events that occurred during or after administration of the first dose of IP in this Extension Study. AE=any untoward medical occurrence in participant administered an IP that does not have causal relationship with treatment. Adverse reaction/suspected adverse reaction=AE that is considered by the investigator to be possibly or probably related to IP administration, or for which the causality is indeterminate or missing, or that begins during infusion of IP or within 72 hours following the end of IP infusion. All local infusion site treatment-emergent AEs were reported as adverse reactions.

25. Number of Participants With Treatment-Emergent Local Tolerability Events During Ramp-up

    Time frame: During the ramp-up (8 weeks)

    Participants with local tolerability events were those for which the infusion rate was reduced and/or the infusion was interrupted or stopped due to intolerability and/or AEs. These events were assessed during the initial ramp-up for each participant i.e., during the first 8 weeks of open-label extension study 161505 [NCT02955355] among participants originally randomized to placebo (as being in the placebo arm, they had no ramp-up during the 161403 [NCT02549170] study) versus during the 8-week ramp-up for participants originally randomized to active HYQVIA in double-blind 161403 study. Thus, the data for this outcome measure are presented per the bifurcation of participants in the study 161403.

26. Number of Participants With Local Infusion Reactions, as a Function of Dosing Interval, Infusion Rate Per Site, and Infusion Volume Per Site

    Time frame: From the first dose of study drug up to end of study (up to 6.6 years)

    Local infusion reactions were defined as local (administration site-related) adverse events. Median infusion rate per site was derived as the median value across all participants, per participant's average infusion rate, by site: actual volume infused / duration in hours of infusion / number of sites. Median infusion volume per site was derived as the median value across all participants, per participant's average actual volume infused, by site: actual volume infused / number of sites. Number of participants with local infusion reactions as a function of each of the categories are presented below.

27. Number of Participants Whose Anti-Hyaluronidase Binding Antibody Titers Rose by ≥4-fold From Baseline

    Time frame: Baseline, up to 6.6 years

    Number of participants whose anti-hyaluronidase antibody titers rose by ≥4 fold from the baseline value at any point during the study was assessed.

28. Number of Participants With Binding Antibodies to rHuPH20

    Time frame: From the first dose of study drug up to end of study (up to 6.6 years)

    Binding antibodies were defined as anti-rHuPH20 titer ≥1:160.

29. Number of Participants With Neutralizing Antibodies Binding to rHuPH20

    Time frame: From the first dose of study drug up to end of study (up to 6.6 years)

30. Number of Participants With a Decline of Anti-rHuPH20 Binding Antibody Titers to the Antibody Titer Level at Baseline in Study 161403 or to <1:160 Antibody Titer Level at the Study Completion or Early Discontinuation

    Time frame: From the first dose of study drug up to end of study (up to 6.6 years)

31. Number of Participants Who Had >1:10,000 Anti-rHuPH20 Binding Antibody Titers With Neutralizing Antibodies

    Time frame: From the first dose of study drug up to end of study (up to 6.6 years)

Results and safety

Loading the posted results from ClinicalTrials.gov…

Research links

• Official record on ClinicalTrials.govLast updated by the sponsor 28 Aug 2024.
• Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
• Derived from this study: PubMed 42578463Bus SR, Wieske L, Keddie S, van Schaik IN, Eftimov F. Subcutaneous immunoglobulin for chronic inflammatory demyelinating polyradiculoneuropathy. Cochrane Database Syst Rev. 2026 Aug 11;8:CD014542. doi: 10.1002/14651858.CD014542.pub2.
• Derived from this study: PubMed 39523874Hadden RDM, Andersen H, Bril V, Basta I, Rejdak K, Duff K, Greco E, Hasan S, Anderson-Smits C, Ay H. Long-term safety and tolerability of hyaluronidase-facilitated subcutaneous immunoglobulin 10% as maintenance therapy for chronic inflammatory demyelinating polyradiculoneuropathy: Results from the ADVANCE-CIDP 3 trial. J Peripher Nerv Syst. 2024 Dec;29(4):441-452. doi: 10.1111/jns.12672. Epub 2024 Nov 11.
• To obtain more information on the study, click here/on this linkLink provided by the sponsor.
• Individual participant dataSharing planned: Yes. Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.

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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.

35 sites in 18 countries: see every site and its status.