Double-Blind, Randomized, Placebo-Controlled Trial of AKST4290 for Adjunctive Treatment of Mild to Moderate Bullous Pemphigoid

• Register: EUCTR
• Last refreshed on: 21 June 2021
• Main ID: EUCTR2019-001059-37-DE
• Date of registration: 11/06/2019
• Prospective Registration: Yes
• Primary sponsor: Alkahest, Inc.
• Public title: Double-Blind, Randomized, Placebo-Controlled Trial of AKST4290 for Adjunctive Treatment of Mild to Moderate Bullous Pemphigoid
• Scientific title: Double-Blind, Randomized, Placebo-Controlled Trial of AKST4290 for Adjunctive Treatment of Mild to Moderate Bullous Pemphigoid
• Date of first enrolment: 21/06/2019
• Target sample size: 30
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2019-001059-37
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Bulgaria, Germany

Contacts

• Name: Jonas Hannestadt, MD, PhD
• Affiliation: Alkahest, Inc.

• Name: Jonas Hannestadt, MD, PhD
• Affiliation: Alkahest, Inc.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Age 60-95 years, inclusive at screening.
2. Clinical diagnosis of mild or moderate BP at screening:
o Mild BP is defined as BPDAI = 10 OR < 10% affected body surface
o Moderate BP is defined as BPDAI = 10 and = 55 OR 10-30% affected body surface
3. Treatment naïve or initiation of whole-body high potency topical steroid treatment < 7 days of screening (lesion-only treatment for any amount of time with any topical steroids prior to screening is allowed without restriction).
4. Female subjects must not be pregnant or breastfeeding. Women of childbearing potential (WOCBP) must have a negative pregnancy test at screening. WOCBP and men must agree to use highly effective contraception (Clinical Trial Facilitation Group 2014) prior to study entry. A woman is considered of childbearing potential following menarche and until becoming postmenopausal (no menses for at least 1 year without an alternative cause). Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in the study, she should inform her treating physician immediately. Male subjects must be willing to use a barrier method contraception while participating in the study.
5. The subject must be able to follow the study procedures and receive the treatment in the established timeframe.
6. The subject must be able to understand the procedures and agree to complete the required assessments.
7. Provide a signed and dated informed consent form in accordance with local regulations and/or IRB/IEC guidelines.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 10
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20

Exclusion criteria:
1. Severe BP (BPDAI score = 56 OR > 30 new blisters per day OR > 30% affected body surface).
2. Initiation of gliptins and other treatments (e.g., etanercept, sulfasalazine, furosemide, penicillin) that can trigger BP if this treatment was started within 4 weeks prior to screening and is considered possibly related to the onset of BP.
3. Initiation of any concomitant medication in the last 3 months prior to screening and assessed by the investigator as possibly related to the development of BP.
4. Planned use of intravenous immunoglobulin or other concomitant treatments for BP (i.e., doxycycline, dapsone) during the study period.
5. Life expectancy of < 6 months (as assessed by the investigator).
6. Use of systemic immunosuppressants (i.e., mycophenolate, azathioprine, methotrexate) within 4 weeks prior to screening.
7. Treatment with rituximab within 1 year prior to screening.
8. Medical history of:
• Myocardial infarction or stroke within 6 months of screening
• Active bleeding disorder
• Major surgery within 1 month of screening or planned within the study period
• Active liver disease
• Positive screening test result for hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), or tuberculosis (TB)(by QuantiFERON testing)
9. Prior treatment within 2 weeks or planned use of strong/potent cytochrome (CYP) P450 3A4/5 (CYP3A4/5) or P-glycoprotein (P-gp) inhibitors or inducers during the study (see Section 17.6.1).
10. Current or planned concomitant use of drugs that are P-gp sensitive substrates and that have a narrow therapeutic index (NTI) (e.g., some factor Xa inhibitors) (see Section 17.6.1).
11. Subjects taking warfarin (see Section 17.6.1).
12. Renal function as defined by estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73 m2 using the Modification of Diet in Renal Disease (MDRD) study equation (see
Section 17.5).
13. Use of systemic steroids (>10 mg prednisone or equivalent/day) within 14 days of first dose of study agent or known diseases (other than BP) that could require the use of systemic steroids within the study period. Subjects who have received a single high-dose of steroids (intravenous or oral) 14 days or more before the administration of the first dose of study drug are eligible for enrollment.
14. Clinically relevant abnormal laboratory value at screening, including hematology, blood chemistry, or urinalysis (laboratory testing may be repeated once during the screening phase).
15. Significant alcohol or drug abuse within past 2 years.
16. Based on ECG reading, subjects with a risk of QT prolongation including:
• A baseline prolongation of QTc (using Fridericia’s formula: = 450 ms in men and = 470 ms in women) with confirmation on a repeat ECG.
• A history of additional risk factors for Torsades de pointes arrhythmia (e.g., heart failure, hypokalemia, family history of Long QT Syndrome, etc.).
17. The use of concomitant medications known to prolong the QT/QTc interval.
18. Significant medical conditions (as determined by medical history, examination, and clinical investigations at screening) that may, in the opinion of the investigator, result in the any of the following:
• Put the subject at risk because of participation in the study.
• Influence the results of the study.
• Cause concern regarding the subject’s ability to participate in the study.
19. Malignancy for which the subject is currently undergoing resection, radiation, or chemotherapy.
20. Participation in studies of i

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Mild to Moderate Bullous Pemphigoid
MedDRA version: 21.1 Level: LLT Classification code 10006567 Term: Bullous pemphigoid System Organ Class: 100000004858

Therapeutic area: Diseases [C] - Skin and Connective Tissue Diseases [C17]

Intervention(s)

Product Name: AKST4290
Product Code: AKST4290
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: AKST4290
CAS Number: 1251528-23-0
Current Sponsor code: AKST4290
Other descriptive name: 2-[[[(2R)-1-[1-[(4-CHLORO-3-METHYLPHENYL)METHYL]-4- PIPERIDINYL]-5-OXO-2-PYRROLIDINYL]CARBONYL]AMINO]- N,N,6-TRIMETHYL-4-PYRIDINECARBOXAMIDE,DIHYDROCHLORIDE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 400-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: At 1-3 weeks depending on when subjects reach disease control.

Primary end point(s): The proportion of subjects who achieve disease control (= 3 new blisters/day and healing of existing blisters) without requiring rescue therapy.

Secondary Objective: To assess treatment safety of the proposed dosing regimen. Additional secondary endpoints include assessment of time to disease control; time to rescue therapy; change in BP Disease Area Index (BPDAI) score by treatment week and at disease control; and change in pruritis as assessed by the BPDAI-Visual Analog Scale (BPDAI-VAS) by treatment week and at disease control. In addition, change in skin (biopsy) eosinophil counts and overall steroid use required to achieve disease control will be assessed.

Main Objective: To investigate the proportion of subjects who achieve disease control (defined as = 3 new blisters/day and healing of existing blisters) following topical steroid treatment with adjunctive AKST4290 without receiving rescue therapy.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: At 1-3 weeks depending on when subjects reach disease control.

Secondary end point(s): • Safety as assessed by the incidence, seriousness, and severity of adverse events (AEs).
• Time to disease control by treatment Day/Week.
• Time to rescue therapy by treatment Day/Week.
• Change from baseline in BPDAI score by treatment Week and at disease control.
• Change from baseline in pruritus as evaluated by the BPDAI-VAS by treatment week and at disease control.
• Change from baseline in skin biopsy eosinophil levels at disease control.
• Evaluation of total cumulative steroid exposure at baseline, by treatment Week and at disease control.
• Evaluation of maximum daily steroid dose at baseline, by treatment Week and at disease control.

Secondary ID(s)

AKST4290-221

Source(s) of Monetary Support

Alkahest, Inc.

Ethics review

Status: Approved
Approval date: 18/06/2019
Contact: