KVD824-201: A Trial to Evaluate the Efficacy and Safety of Different Doses of KVD824 for Prophylactic Treatment of HAE Type I or II

• Sponsor: KalVista Pharmaceuticals, Ltd. (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT05055258
• Collaborator: (none)
• Enrollment: 48
• Locations: 35
• Arms: 4
• Anticipated Duration (Months): 22.1
• Patients Per Site: 1.4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

A study to assess whether different doses of KVD824 are effective in preventing attacks of Hereditary Angiodedema Type I or Type II.

Condition or Disease	Intervention/Treatment	Phase
Angioedema, Hereditary, Types I and II	Drug: KVD824; Drug: Placebo to KVD824	Phase 2

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 48 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Randomized, Double-Blind, Placebo-Controlled, Phase 2 Trial to Evaluate the Efficacy and Safety of 3 Dose Levels of KVD824, an Oral Plasma Kallikrein Inhibitor, for Long-Term Prophylactic Treatment of Hereditary Angioedema Type I or II
• Actual Study Start Date: Sep 27, 2021
• Anticipated Primary Completion Date: Jul 31, 2023
• Anticipated Study Completion Date: Jul 31, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 300 mg KVD824 300 mg KVD824 twice a day for 12 weeks	Drug: KVD824; KVD824 300 mg Modified-Release Tablets
Experimental: 600 mg KVD824 Two 300 mg KVD824 tablets twice a day for 12 weeks	Drug: KVD824; KVD824 300 mg Modified-Release Tablets
Experimental: 900 mg KVD824 Three 300 mg KVD824 tablets twice a day for 12 weeks	Drug: KVD824; KVD824 300 mg Modified-Release Tablets
Placebo Comparator: Placebo to KVD824 One, two or three placebo tablets to be taken twice a day for 12 weeks	Drug: Placebo to KVD824; Placebo to KVD824 300 mg Modified-Release Tablets

Outcome Measures

Primary Outcome Measures

1. The Rate of Investigator-confirmed HAE attacks during the Treatment Period [12 weeks]

   To examine the number of investigator-confirmed attacks whilst on treatment compared to placebo

Secondary Outcome Measures

1. Proportion of subjects without Investigator-confirmed HAE attacks during the Treatment Period. [12 weeks]

2. Rate of Investigator-confirmed HAE attacks that require conventional treatment during the Treatment Period. [12 weeks]

3. Angioedema Quality of Life Questionnaire (AE-QoL) total score and domain scores during the Treatment Period. [12 weeks]

   AE-QoL is a quality of life questionnaire with a range of 0 (minimum) to 100 (maximum). A total score of 100 indicates worst possible impairment.

4. Angioedema Control Test (AECT) score and domain scores during the Treatment Period. [12 weeks]

   AECT is a 4-item patient-reported outcome measure. The total score is from 0 (minimum) to 16 (maximum). A higher score indicates a higher level of angioedema control.

5. Proportion of subjects with an AECT score ≥12 at the end of the Treatment Period. [12 weeks]

   AECT is a 4-item patient-reported outcome measure. The total score is from 0 (minimum) to 16 (maximum). A higher score indicates a higher level of angioedema control.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Male or female subjects 18 years of age and older.

2. Confirmed diagnosis of HAE type I or II at any time in the medical history:

3. Documented clinical history consistent with HAE (subcutaneous or mucosal, nonpruritic swelling episodes without accompanying urticaria) AND EITHER

4. Diagnostic testing results obtained prior to randomization that confirm HAE Type I or II: 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. Testing may be obtained from central or local laboratories or obtained from documented historical testing results. Subjects may be restested at anytime prior to randomization if results are incongruent with clinical history or believed by the Investigator to be confounded by recent prophylactic or therapeutic C1 INH use, OR

5. Documented genetic results that confirm known mutations for HAE Type I or II.

6. Subject has access to and ability to use conventional treatment for HAE attacks.

7. Subject is willing to cease any current medications being taken for HAE prophylaxis and Investigator determines that doing so would not place the subject at any undue safety risk.

8. Subject's last dose of attenuated androgens was at least 28 days prior to first dose of IMP.

9. During the Run-in Period subject meets one of the following criteria:

10. Two Investigator-confirmed attacks in the first 4-week period.

11. Three Investigator-confirmed attacks in ≤8 weeks.

12. Subjects who are fertile and heterosexually active must adhere to contraception requirements throughout the trial as follows:

1. Female subjects must agree to use at least one highly effective contraception method from the Screening Visit until the end of the trial. Highly effective methods of contraception include: i) Progestogen-only hormonal contraception associated with inhibition of ovulation: oral/injectable/implantable (hormonal contraception that contains estrogen including ethinylestradiol is excluded per Exclusion 4).

1. Intrauterine device (IUD). iii) Intrauterine hormone-releasing system (IUS). iv) Bilateral tubal occlusion. v) Vasectomized partner (provided that the partner is the sole sexual partner of the female subject of childbearing potential and that the vasectomized partner has received medical assessment of surgical success).

1. Male subjects with a female partner of childbearing potential must agree to use condoms for the entire Treatment Period AND for 90 days following the final dose of investigational medicinal product (IMP). Female partners are encouraged to use contraception as outlined in Inclusion 7a) from the Screening Visit until the end of the trial. Hormonal contraception that contains estrogen including ethinylestradiol is acceptable for the female partner.

1. Subjects who are not fertile or not sexually active, as defined below, do not require contraception.

2. Subjects who refrain from heterosexual intercourse during the trial if the reliability of the heterosexual abstinence has been evaluated in relation to the duration of the clinical trial and is the preferred and usual lifestyle of the subject.

3. Male subjects who are surgically sterile (e.g. vasectomized with medical assessment of surgical success).

4. Female subjects who are surgically sterile (e.g. status post hysterectomy, bilateral oophorectomy, or bilateral tubal ligation) or post menopausal for at least 12 months.

5. Subjects must be able to swallow trial tablets whole.

6. Subjects assessed by the Investigator must be able to appropriately receive and store IMP, and be able to read, understand, and complete the eDiary.

7. Investigator believes that the subject is willing and able to adhere to all protocol requirements.

8. Subject provides signed informed consent and is willing and capable of complying with trial requirements and procedures.

Exclusion Criteria

1. Any concomitant diagnosis of another form of chronic angioedema, such as acquired C1 inhibitor deficiency, HAE with normal C1-INH (previously known as HAE type III), idiopathic angioedema, or angioedema associated with urticaria.

2. A clinically significant history of poor response to C1-INH therapy or plasma kallikrein inhibitor therapy for the management of HAE, in the opinion of the Investigator.

3. Use of angiotensin converting enzyme (ACE) inhibitors after the Screening Visit or within 7 days prior to randomization.

4. Any estrogen containing medications with systemic absorption (such as oral contraceptives including ethinylestradiol or hormonal replacement therapy) after the Screening Visit or within 7 days prior to randomization.

5. Use of narrow therapeutic index drugs metabolized by CYP3A4 or CYP2C9 or transported by OAT1, OCT2, and OATP1B1, starting at screening, as determined by the Investigator.

6. Use of strong CYP3A4 inhibitors and inducers during participation in the trial, starting at the Screening Visit.

Note: These medications include but are not limited to the following:

Inhibitors: boceprevir, clarithromycin, cobicistat, dasabuvir, denoprevir, elvitegravir, idelalisib, indinavir, itraconazole, ketoconazole, lopinavir, nefazodone, nelfinavir ombitasvir, paritaprevir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, tipranavir, troleandomycin, and voriconazole.

Inducers: apalutamide, carbamazepine, enzalutamide, mitotane, phenytoin, rifampin, St. John's Wort.

1. Inadequate organ function, including but not limited to;

2. Alanine aminotransferase (ALT) > 2x Upper limit of Normal (ULN).

3. Aspartate aminotransferase (AST) > 2x ULN.

4. Bilirubin direct > 1.25x ULN.

5. International normalized ratio (INR) > 1.2.

6. Clinically significant hepatic impairment defined as a Child-Pugh B or C.

7. Estimated glomerular filtration rate (eGFR) <60 mL/min.

8. Any clinically significant comorbidity or systemic dysfunction that in the opinion of the Investigator would jeopardize the safety of the subject by participating in the trial.

9. History of substance abuse or dependence that would interfere with the completion of the trial, as determined by the Investigator.

10. Known hypersensitivity to KVD824 or placebo or to any of the excipients.

11. Any prior use of any gene therapy treatment for HAE.

12. Participation in any interventional investigational clinical trial, including an investigational COVID-19 vaccine trial, within 4 weeks of the last dosing of investigational drug prior to screening.

13. Any pregnant or breastfeeding subject.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	KalVista Investigative Site	Birmingham	Alabama	United States	35294
2	KalVista Investigative Site	Scottsdale	Arizona	United States	85251
3	KalVista Investigative Site	La Jolla	California	United States	92093
4	KalVista Investigative Site	Santa Monica	California	United States	90404
5	KalVista Investigative Site	Walnut Creek	California	United States	94598
6	KalVista Investigative Site	Centennial	Colorado	United States	80112
7	KalVista Investigative Site	Tampa	Florida	United States	33620
8	KalVista Investigative Site	Chevy Chase	Maryland	United States	20815
9	KalVista Investigative Site	Boston	Massachusetts	United States	02114
10	KalVista Investigative Site	Saint Louis	Missouri	United States	63110
11	KalVista Investigative Site	Cincinnati	Ohio	United States	45231
12	KalVista Investigative Site	Hershey	Pennsylvania	United States	17033
13	KalVista Investigative Site	Dallas	Texas	United States	75390
14	KalVista Investigative Site	Spokane	Washington	United States	99204
15	KalVista Investigative Site	Campbelltown	New South Wales	Australia
16	KalVista Investigative Site	Adelaide	South Australia	Australia
17	KalVista Investigative Site	Sofia		Bulgaria
18	KalVista Investigative Site	North York	Ontario	Canada
19	KalVista Investigative Site	Brno		Czechia
20	KalVista Investigative Site	Praha		Czechia
21	KalVista Investigative Site	Grenoble		France
22	KalVista Investigative Site	Paris		France
23	KalVista Investigative Site	Mainz	Rheinland-Pfalz	Germany
24	KalVista Investigative Site	Berlin		Germany
25	KalVista Investigative Site	Frankfurt am main		Germany
26	KalVista Investigative Site	Budapest		Hungary
27	KalVista Investigative Site	Milan		Italy
28	KalVista Investigative Site	Padova		Italy
29	KalVista Investigative Site	Grafton	Auckland	New Zealand
30	KalVista Investigative Site	Skopje		North Macedonia
31	KalVista Investigative Site	San Juan		Puerto Rico
32	KalVista Investigative Site	Birmingham		United Kingdom
33	KalVista Investigative Site	Leeds		United Kingdom
34	KalVista Investigative Site	London		United Kingdom
35	KalVista Investigative Site	Newcastle Upon Tyne		United Kingdom

Sponsors and Collaborators

• KalVista Pharmaceuticals, Ltd.

Investigators

• Study Director: Study Director, KalVista Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: KalVista Pharmaceuticals, Ltd.
• ClinicalTrials.gov Identifier: NCT05055258
• Other Study ID Numbers: KVD824-201
• First Posted: Sep 24, 2021
• Last Update Posted: Aug 10, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by KalVista Pharmaceuticals, Ltd.: KVD824; KOMPLETE
• Additional relevant MeSH terms: Angioedema; Angioedemas, Hereditary; Hereditary Angioedema Types I and II

Study Results

No Results Posted as of Aug 10, 2022