A Phase 3 interventional study of TAK-667 in Hereditary Angioedema, sponsored by Takeda. Completed at 3 sites in Japan. Open to participants aged 2 Years to 17 Years. Per ClinicalTrials.gov, last updated 2022-03-29.
Sponsored by Takeda · Phase 3, Interventional, and Treatment
The main aim of the study is to check for side effects from icatibant in children and teenagers with hereditary angioedema (HAE). Other aims are to check how well icatibant controls HAE symptoms in these children and teenagers, and how much icatibant stays in their blood.
At the first visit, the study doctor will check if each child or teenager can take part. For those who can take part, participants and their parents or caregivers will visit the clinic or hospital when they have their next HAE attack. Participants will receive 1 injection (shot) of icatibant in a vein and will stay at the clinic or hospital until their HAE symptoms are under control. Participants can receive up to 2 more injections of icatibant over time if their HAE symptoms don't improve or get worse.
After the participants go home, the study staff will follow up with them by a telephone call 1 to 2 days later. Then, the participants will visit the clinic or hospital 1 week after they received the icatabant injection.
The participant can visit the clinic or hospital and be treated with icatibant in the same way for up to 3 HAE attacks in total.
The drug being tested in this study is called TAK-667. TAK-667 is being tested to treat Japanese Children and Adolescents who experience acute attack of HAE. This study will look at safety, efficacy and pharmacokinetics (PK) of people who take TAK-667.
The study will enroll at least up to 3 participants. Participants will take TAK-667 with SC administration on the abdomen. The dose of TAK-667 will be dependent on the participant's body weight (Up to 30 mg; 10 mg for 12 kg to 25 kg, 15 mg for 26 kg to 40 kg, 20 mg for 41 kg to 50kg, 25 mg for 51 kg to 65 kg, 30 mg for >65 kg).
This multi-center trial will be conducted in Japan. The overall time to participate in this study is 25 days as a maximum (screening day for initial attack plus 8 days post dose for each 3 attacks as a maximum). Participants will make multiple visits to the clinic and will be closely monitored in the hospital/study center for at least 8 hours after administration and receive physical examination and assessment to evaluate safety, efficacy and PK. Hospitalization may be prolonged until, in the opinion of the investigator, the participant is clinically stable and onset of HAE attack is completely resolved.
173 studies on the registry are indexed under Angioedemas, Hereditary; 25 are open to participants now.
This study's enrollment of 2 is below the median of 48 across 117 interventional studies indexed under Angioedemas, Hereditary.
Browse Angioedemas, Hereditary studies →Takeda is the lead sponsor of 1,025 studies on the registry; 92 are open to participants now.
Of its 177 completed or terminated interventional studies of FDA-regulated products, 153 (86%) have results posted.
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The participant who has a documented and confirmed diagnosis of HAE type I or II. Diagnosis may be based on historical data using the following criteria:
If the participant does not have a documented and confirmed diagnosis of HAE type I or II based on historical data, including C1-INH deficiency, the participant's diagnosis must be determined prior to treatment by C1-INH test results which demonstrate a functional C1-INH deficiency.
Exclusion Criteria:
TAK-667, single SC administration on the abdomen on Day 1. The dose of TAK-667 will be dependent on the participant's body weight (Up to 30 mg; 10 mg for 12 kg to 25 kg, 15 mg for 26 kg to 40 kg, 20 mg for 41 kg to 50kg, 25 mg for 51 kg to 65 kg, 30 mg for \>65 kg).
Drug: TAK-667
TAK-667 single SC administration
Also known as: Icatibant
Number of Participants Who Experienced at Least One Treatment-Emergent Adverse Events (TEAE)
An adverse event (AE) means any untoward medical occurrence in a participant administered a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it is related to the medicinal product. A treatment-emergent adverse event (TEAE) was defined as any adverse event occurring after the start of Icatibant administration of the treatment period.
Time frame: Up to approximately 6 months
Number of Participants With Injection Site Reactions
Injection sites were examined for erythema, swelling, cutaneous pain, burning sensation, itching/pruritus, and warm sensation. Data for injection site reactions were collected separately from general reports of AEs. As pre-defined in the protocol, an injection site reaction not meeting SAE criteria was not required to be reported additionally as an AE.
Time frame: Postdose, up to Day 8
Number of Participants Who Experienced at Least One TEAE Related to Resting 12-lead Electrocardiogram
An AE means any untoward medical occurrence in a participant administered a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it is related to the medicinal product. A TEAE was defined as any AE occurring after the start of Icatibant administration of the Treatment Period. A resting 12-lead ECG was recorded and reported for participants shifts from within normal limits at baseline to abnormal, but not clinically significant, or abnormal and clinically significant after study drug administration.
Time frame: Up to approximately 6 months
Number of Participants Who Experienced at Least One TEAE Related to Vital Sign
An AE means any untoward medical occurrence in a participant administered a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it is related to the medicinal product. A TEAE was defined as any AE occurring after the start of Icatibant administration of the Treatment Period. Vital signs included body temperature (oral), sitting blood pressure (after 5 minutes resting), respiration rate and pulse (beats per minute \[bpm\]).
Time frame: Up to approximately 6 months
Number of Participants Who Experienced at Least One TEAE Related to Clinical Laboratory Parameters
An AE means any untoward medical occurrence in a participant administered a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it is related to the medicinal product. A TEAE was defined as any AE occurring after the start of Icatibant administration of the Treatment Period. The laboratory parameters included hematology, serum chemistries, and urinalysis.
Time frame: Up to approximately 6 months
Number of Participants Who Experience at Least One TEAE Related to Clinically Significant Changes in Reproductive Hormones
An AE means any untoward medical occurrence in a participant administered a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it is related to the medicinal product. A TEAE was defined as any AE occurring after the start of Icatibant administration of the Treatment Period. Blood samples were collected to assess follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol, and progesterone in females, and FSH, LH, and testosterone in males.
Time frame: Up to approximately 6 months
Number of Participants Who Reported Presence of Anti-icatibant Antibodies
Serum samples for immunogenicity testing were collected for determination of anti-icatibant antibodies. If hypersensitivity was observed, it was reported as an AEs of special interest. An AE means any untoward medical occurrence in a participant administered a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it is related to the medicinal product.
Time frame: Up to approximately 6 months
Time to Onset of Symptom Relief With Investigator-Rated Symptom Scores Assessed by Investigator
The time to onset of symptom relief, defined as the duration of time in hours from the time of icatibant administration to the earliest time at which at least a 20% improvement is observed in the average post-treatment score with no worsening of any single component score. Investigator-rated symptom score was used for assessment and scoring of cutaneous, abdominal, and laryngeal symptoms of acute HAE attacks related to daily activities. The score ranged from 0 to 4 and each number of scores meant the following: 0 = none; absence of symptoms, 1 = mild (no to mild interference with daily activities), 2 = moderate (moderate interference with daily activities), 3 = severe (severe interference with daily activities), 4 = very severe (very severe interference with daily activities).
Time frame: Baseline, and post dose on Day 1
Time to Onset of Symptom Relief With Faces Pain Scale-Revised (FPS-R) Scores for Participants of 4 Years Age and Older
The time to onset of symptom relief, defined as the duration of time in hours from the time of icatibant administration to the earliest time at which the post-treatment score improved by at least 1 level. Participants of 4 years age and older self-assessed their HAE-related pain using the FPS-R instrument. FPS-R is a self-reported measure used to assess the intensity of children's pain and it is scored using a 0 to 10 scale (0=no pain to 10=very much pain).
Time frame: Baseline, and post dose on Day 1
Time to Onset of Symptom Relief by Faces, Legs, Activity, Cry, and Consolability (FLACC) Scale Assessed by Investigator for Participants of Younger Than 4 Years Age
The time to onset of symptom relief, defined as the earliest time at which a 20% improvement is observed in the total post-treatment score. Participants of younger than 4 years age underwent investigator assessment of HAE-related pain (cutaneous, abdominal, and laryngeal) using the FLACC compartmental pain scale. Each of the 5 categories were scored from 0 to 2. Face(F): 0 (no particular expression/smile) - 2 (frequent to constant frown clenched jaw quivering chin); Legs(L): 0 (normal position/relaxed) - 2 (kicking/legs drawn up); Activity(A): 0 (lying quietly, normal position, moves easily) - 2 (arched rigid/jerking); Cry(C): 0 (No cry \[awake/asleep\]) - 2 (crying steadily/screams/sobs or frequent complaints); Consolability(C): 0 (content/relaxed) - 2 (difficult to console/comfort), resulting in a total score between 0 and 10.
Time frame: Baseline, and post dose on Day 1
Number of Participants Who Were Treated With Rescue Medication During Study
Rescue medication included therapies for HAE used for HAE attack and symptomatic treatment used in order to improve symptoms of angioedema (eg, pain and nausea).
Time frame: Up to approximately 6 months
Number of Participants With Worsened Intensity of Clinical HAE Symptoms Between 2 and 4 Hours After Treatment With SC Icatibant Using Investigator-Rated Symptom Scores
Investigator-rated symptom score was used for assessment and scoring of cutaneous, abdominal, and laryngeal symptoms of acute HAE attacks related to daily activities. The score ranged from 0 to 4 and each number of scores means following; 0 = none; absence of symptoms, 1 = mild (no to mild interference with daily activities), 2 = moderate (moderate interference with daily activities), 3 = severe (severe interference with daily activities), 4 = very severe (very severe interference with daily activities).
Time frame: From 2 hours post-dose to 4 hours post-dose
Time to Initial Symptom Improvement Reported by Investigator
Time to initial symptom improvement reported by investigator, was defined as the duration of time in hours from icatibant administration until the time when overall participant improvement was first noted by investigator.
Time frame: Up to 8 hours post dose (or till the onset of HAE attacks were resolved)
Time to Initial Symptom Improvement Reported by Participant
Time to initial symptom improvement reported by participant, defined as the duration of time in hours from icatibant administration until the time when overall participant improvement was first noted by participant, participant's parent or participant's legal guardian.
Time frame: Up to 8 hours post dose (or till the onset of HAE attacks were resolved)
Plasma Concentration for TAK-667
Time frame: Day 1 pre-dose and at multiple timepoints post-dose
Plasma Concentration for TAK-667 Metabolite M-I
Time frame: Day 1 pre-dose and at multiple timepoints post-dose
Plasma Concentration for TAK-667 Metabolite M-II
Time frame: Day 1 pre-dose and at multiple timepoints post-dose
Participants took part in the study at 2 investigative sites in Japan from 15 January 2021 to 27 July 2021.
| Milestone | TAK-667 10-30 mg |
|---|---|
| Started | 2 |
| Completed | 2 |
| Not completed | 0 |
An adverse event (AE) means any untoward medical occurrence in a participant administered a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it is related to the medicinal product. A treatment-emergent adverse event (TEAE) was defined as any adverse event occurring after the start of Icatibant administration of the treatment period.
| Participants | TAK-667 10-30 mg |
|---|---|
| Number of Participants Who Experienced at Least One Treatment-Emergent Adverse Events (TEAE) | 0 |
Injection sites were examined for erythema, swelling, cutaneous pain, burning sensation, itching/pruritus, and warm sensation. Data for injection site reactions were collected separately from general reports of AEs. As pre-defined in the protocol, an injection site reaction not meeting SAE criteria was not required to be reported additionally as an AE.
| percentage of participants | TAK-667 10-30 mg |
|---|---|
| Number of Participants With Injection Site Reactions | 2 |
An AE means any untoward medical occurrence in a participant administered a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it is related to the medicinal product. A TEAE was defined as any AE occurring after the start of Icatibant administration of the Treatment Period. A resting 12-lead ECG was recorded and reported for participants shifts from within normal limits at baseline to abnormal, but not clinically significant, or abnormal and clinically significant after study drug administration.
| Participants | TAK-667 10-30 mg |
|---|---|
| Number of Participants Who Experienced at Least One TEAE Related to Resting 12-lead Electrocardiogram | 0 |
An AE means any untoward medical occurrence in a participant administered a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it is related to the medicinal product. A TEAE was defined as any AE occurring after the start of Icatibant administration of the Treatment Period. Vital signs included body temperature (oral), sitting blood pressure (after 5 minutes resting), respiration rate and pulse (beats per minute \[bpm\]).
| Participants | TAK-667 10-30 mg |
|---|---|
| Number of Participants Who Experienced at Least One TEAE Related to Vital Sign | 0 |
An AE means any untoward medical occurrence in a participant administered a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it is related to the medicinal product. A TEAE was defined as any AE occurring after the start of Icatibant administration of the Treatment Period. The laboratory parameters included hematology, serum chemistries, and urinalysis.
| Participants | TAK-667 10-30 mg |
|---|---|
| Number of Participants Who Experienced at Least One TEAE Related to Clinical Laboratory Parameters | 0 |
An AE means any untoward medical occurrence in a participant administered a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it is related to the medicinal product. A TEAE was defined as any AE occurring after the start of Icatibant administration of the Treatment Period. Blood samples were collected to assess follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol, and progesterone in females, and FSH, LH, and testosterone in males.
| Participants | TAK-667 10-30 mg |
|---|---|
| Number of Participants Who Experience at Least One TEAE Related to Clinically Significant Changes in Reproductive Hormones | 0 |
Serum samples for immunogenicity testing were collected for determination of anti-icatibant antibodies. If hypersensitivity was observed, it was reported as an AEs of special interest. An AE means any untoward medical occurrence in a participant administered a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it is related to the medicinal product.
| Participants | TAK-667 10-30 mg |
|---|---|
| Number of Participants Who Reported Presence of Anti-icatibant Antibodies | 0 |
The time to onset of symptom relief, defined as the duration of time in hours from the time of icatibant administration to the earliest time at which at least a 20% improvement is observed in the average post-treatment score with no worsening of any single component score. Investigator-rated symptom score was used for assessment and scoring of cutaneous, abdominal, and laryngeal symptoms of acute HAE attacks related to daily activities. The score ranged from 0 to 4 and each number of scores meant the following: 0 = none; absence of symptoms, 1 = mild (no to mild interference with daily activities), 2 = moderate (moderate interference with daily activities), 3 = severe (severe interference with daily activities), 4 = very severe (very severe interference with daily activities).
| hours | TAK-667 10-30 mg |
|---|---|
| Time to Onset of Symptom Relief With Investigator-Rated Symptom Scores Assessed by Investigator | NA (0.9 to 1.0) |
The time to onset of symptom relief, defined as the duration of time in hours from the time of icatibant administration to the earliest time at which the post-treatment score improved by at least 1 level. Participants of 4 years age and older self-assessed their HAE-related pain using the FPS-R instrument. FPS-R is a self-reported measure used to assess the intensity of children's pain and it is scored using a 0 to 10 scale (0=no pain to 10=very much pain).
| hours | TAK-667 10-30 mg |
|---|---|
| Time to Onset of Symptom Relief With Faces Pain Scale-Revised (FPS-R) Scores for Participants of 4 Years Age and Older | NA (0.9 to 1.0) |
The time to onset of symptom relief, defined as the earliest time at which a 20% improvement is observed in the total post-treatment score. Participants of younger than 4 years age underwent investigator assessment of HAE-related pain (cutaneous, abdominal, and laryngeal) using the FLACC compartmental pain scale. Each of the 5 categories were scored from 0 to 2. Face(F): 0 (no particular expression/smile) - 2 (frequent to constant frown clenched jaw quivering chin); Legs(L): 0 (normal position/relaxed) - 2 (kicking/legs drawn up); Activity(A): 0 (lying quietly, normal position, moves easily) - 2 (arched rigid/jerking); Cry(C): 0 (No cry \[awake/asleep\]) - 2 (crying steadily/screams/sobs or frequent complaints); Consolability(C): 0 (content/relaxed) - 2 (difficult to console/comfort), resulting in a total score between 0 and 10.
No measurements were reported for this outcome.
Rescue medication included therapies for HAE used for HAE attack and symptomatic treatment used in order to improve symptoms of angioedema (eg, pain and nausea).
| Participants | TAK-667 10-30 mg |
|---|---|
| Number of Participants Who Were Treated With Rescue Medication During Study | 0 |
Investigator-rated symptom score was used for assessment and scoring of cutaneous, abdominal, and laryngeal symptoms of acute HAE attacks related to daily activities. The score ranged from 0 to 4 and each number of scores means following; 0 = none; absence of symptoms, 1 = mild (no to mild interference with daily activities), 2 = moderate (moderate interference with daily activities), 3 = severe (severe interference with daily activities), 4 = very severe (very severe interference with daily activities).
| Participants | TAK-667 10-30 mg |
|---|---|
| Number of Participants With Worsened Intensity of Clinical HAE Symptoms Between 2 and 4 Hours After Treatment With SC Icatibant Using Investigator-Rated Symptom Scores | 0 |
Time to initial symptom improvement reported by investigator, was defined as the duration of time in hours from icatibant administration until the time when overall participant improvement was first noted by investigator.
| hours | TAK-667 10-30 mg |
|---|---|
| Time to Initial Symptom Improvement Reported by Investigator | NA (0.3 to 1.0) |
Time to initial symptom improvement reported by participant, defined as the duration of time in hours from icatibant administration until the time when overall participant improvement was first noted by participant, participant's parent or participant's legal guardian.
| hours | TAK-667 10-30 mg |
|---|---|
| Time to Initial Symptom Improvement Reported by Participant | NA (0.3 to 1.0) |
| ug/l | TAK-667 10-30 mg |
|---|---|
| Baseline (pre-dose) | 0 (0 to 0) |
| 0.5 hours postdose | NA (962 to 978) |
| 1 hour postdose | NA (856 to 882) |
| 2 hours postdose | NA (401 to 410) |
| 4 hours postdose | NA (38.8 to 68.9) |
| ug/l | TAK-667 10-30 mg |
|---|---|
| Baseline (pre-dose) | 0 (0 to 0) |
| 0.5 hours postdose | NA (103 to 106) |
| 1 hour postdose | NA (187 to 223) |
| 2 hours postdose | NA (220 to 247) |
| 4 hours postdose | NA (124 to 137) |
| ug/l | TAK-667 10-30 mg |
|---|---|
| Baseline (pre-dose) | 0 (0 to 0) |
| 0.5 hours postdose | NA (103 to 116) |
| 1 hour postdose | NA (184 to 216) |
| 2 hours postdose | NA (227 to 276) |
| 4 hours postdose | NA (147 to 151) |
Collected over Up to approximately 6 months. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| TAK-667 10-30 mg | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) |
All enrolled participants.
| Age, Continuous(years) | TAK-667 10-30 mg |
|---|
| Sex: Female, Male(Participants) | TAK-667 10-30 mg |
|---|---|
| Female | — |
| Male | — |
| Ethnicity (NIH/OMB)(Participants) | TAK-667 10-30 mg |
|---|---|
| Hispanic or Latino | — |
| Not Hispanic or Latino | — |
| Unknown or Not Reported | — |
| Race (NIH/OMB)(Participants) | TAK-667 10-30 mg |
|---|---|
| American Indian or Alaska Native | — |
| Asian | — |
| Native Hawaiian or Other Pacific Islander | — |
| Black or African American | — |
| White | — |
| More than one race | — |
| Unknown or Not Reported | — |
| Region of Enrollment(Participants) | TAK-667 10-30 mg |
|---|---|
| Japan | 2 |
Documents are hosted by the registry — open the source record to download them.
Plan to share: No — De-identified individual participant data from this particular study will not be shared as there is a reasonable likelihood that individual patients could be re-identified (due to the limited number of study participants/study sites).
Ran from Jan 2021 to primary completion in Jul 2021, 6 months.
Results were first posted in Mar 2022, 8 months after primary completion.
Of 49 industry-sponsored phase 3 interventional studies under Angioedemas, Hereditary, half reached primary completion within 23 months of starting (the median), counting those still running; a quarter within 16 and three quarters within 33. This study's 6 months is below that.
Counting every sponsor, half of 49 studies reached it within 23 months; a quarter within 16 and three quarters within 33.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Jan 2022. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Icatibant