E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hereditary angioedema (HAE) |
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E.1.1.1 | Medical condition in easily understood language |
Long-term, debilitating and life-threatening disease that manifests clinically as unpredictable, intermittent attacks of edema of the face, larynx, gastrointestinal tract, limbs and/or genitalia |
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E.1.1.2 | Therapeutic area | Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10075280 |
E.1.2 | Term | Hereditary angioedema attack |
E.1.2 | System Organ Class | 100000004850 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy of DX-2930 in preventing HAE attacks |
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E.2.2 | Secondary objectives of the trial |
To evaluate the safety of repeated subcutaneous administrations of DX-2930 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Males and females 12 years of age or older at the time of screening
2. Documented diagnosis of HAE (Type I or II) based upon all of the following :
- Documented clinical history consistent with HAE (subcutaneous or mucosal nonpruritic swelling episodes without accompanying urticaria)
- Diagnostic testing results obtained during screening that confirm HAE Type I or II :
C1 inhibitor (C1-INH) functional level < 40% of the normal level. Subjects with functional C1-INH level 40-50% of the normal level may be enrolled if they also have a C4 level below the normal range.
Subjects may begin participating in the run-in period before these diagnostic results are available.
Subjects may be retested if results are incongruent with clinical history or believed by the Investigator to be confounded by recent LTP use.
- At least one of the following : age at reported onset of first angioedema symptoms ≤ 30 years, a family history consistent with HAE Type I or II, or C1q within normal range.
3. Experiencing a baseline rate of at least 1 Investigator-confirmed HAE attack per 4 weeks as confirmed during the run-in period.
4. Adult subjects and caregivers of subjects under the age of 18 are willing and able to read, understand, and sign an informed consent form. Subjects age to 12 to 17, whose caregiver provides informed consent, and are willing and able to read, understand and sign an assent form.
5. Males and females who are fertile and sexually active must adhere to contraception requirements for the duration of the study as follows:
- Females of childbearing potential must agree to be abstinent or it is recommended to use highly effective forms of contraception from screening through 30 days after the final study visit. This includes progestin-only oral contraceptive associated with inhibition of ovulation (oral, injectable, or implantable), intra-uterine device (IUD, all types) or intrauterine hormone releasing system (IUS). Notes: 1) A female whose male partner has had a vasectomy must agree to use one additionnal form of medically acceptable contraception. 2) Use of a male condom with or without spermicide or cervical cap, diaphragm or sponge with spermicide or a combination (double-barrier methods) is not considered highly effective.
- Females of non-childbearing potential, defined as surgically sterile (status post hysterectomy, bilateral oophorectomy, or bilateral tubal ligation) or post-menopausal for at least 12 months do not require contraception during the study.
- Males, including males who are surgically sterile (post vasectomy), with female partners of childbearing potential must agree to be abstinent or else use a medically acceptable form of contraception from screening through 60 days after the final study visit. |
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E.4 | Principal exclusion criteria |
1. Concomitant diagnosis of another form of chronic, recurrent angioedema, such as acquired angioedema (AAE), HAE with normal C1-INH (also known as HAE Type III), idiopathic angioedema, or recurrent angioedema associated with urticaria.
2. Participation in a prior DX-2930 study.
3. Dosing with an investigational drug or exposure to an investigational device within 4 weeks prior to screening.
4. Exposure to angiotensin-converting enzyme (ACE) inhibitors or any estrogen-containing medications with systemic absorption (such as oral contraceptives or hormonal replacement therapy) within 4 weeks prior to screening.
5. Exposure to androgens (e.g. stanozolol, danazol, oxandrolone, methyltestosterone, testosterone) within 2 weeks prior to entering the run-in period.
6. Use of long-term prophylaxis for HAE (C1-INH, attenuated androgens, anti-fibrinolytics) within 2 weeks prior to entering the run-in period.
7. Use of short-term prophylaxis for HAE within 7 days prior to entering the run-in period. Short-term prophylaxis is defined as C1-INH, attenuated androgens, or anti-fibrinolytics used to avoid angioedema complications from medically indicated procedures.
8. Any of the following liver function test abnormalities : alanine aminotransferase (ALT) > 3x upper limit of normal, or aspartate aminotransferase (AST) >3x upper limit of normal, or total bilirubin > 2x upper limit of normal (unless the bilirubin elevation is a result of Gilbert's Syndrome).
9. Pregnancy or breastfeeding.
10. Subject has any condition that, in the opinion of the Investigator or Sponsor, may compromise their safety or compliance, preclude successful conduct of the study, or interfere with interpretation of the results (e.g. history of substance abuse or dependence, significant pre-existing illness or other major comorbidity that the Investigator considers may confound the interpretation of study results). |
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E.5 End points |
E.5.1 | Primary end point(s) |
Number of Investigator-confirmed HAE attacks during the efficacy evaluation period (Day 0 through Day 182) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Day 0 (Visit 1) to Day 182 (Visit 14) |
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E.5.2 | Secondary end point(s) |
1. Number of Investigator-confirmed HAE attacks requiring acute treatment during the efficacy evaluation period (Day 0 through Day 182)
2. Number of moderate or severe Investigator-confirmed HAE attacks during the efficacy evaluation period (Day 0 through Day 182)
3. Number of Investigator-confirmed HAE attacks occuring on Day 14 after administration of study drug through Day 182 (Day 14 through Day 182)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Day 0 (Visit 1) to Day 182 (Visit 14) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 7 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
Germany |
Italy |
United Kingdom |
United States |
Jordan |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |