Double-blind placebo-controlled clinical trial (Phase 1b/2a) to evaluate safety and efficacy of IM-250 administration in patients with recurrent genital herpes.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Innovative Molecules GmbH

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02], Diseases [C] - Skin and Connective Tissue Diseases [C17]

Trial duration

16 Jan 2025 → ongoing

Decision date (initial)

2024-12-18

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Innovative Molecules GmbH

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Pharmacokinetic

To obtain clinical proof of concept for IM-250 in suppressive therapy of genital herpes by investigating different dosing regimens.

Secondary objectives 2

1. • To define safety and tolerability profile of multiple doses of IM-250 in patients with genital herpes.
2. • To describe the pharmacokinetics (PK) in patients receiving different dosing regimens of IM-250.

Conditions and MedDRA coding

Genital herpes infection

Regulatory references

Scientific advice from competent authorities

Federal Institute For Drugs And Medical Devices, Food And Drug Administration

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. 1. Age 18-65 years inclusive at the time of consent.
2. 2. Men or women who agree to comply with any applicable contraceptive requirements of the protocol.
3. 3. Prior history of genital HSV-2, acquired at least 12 months prior to screening according to patient’s report. The laboratory confirmation of HSV-2 infection by positive PCR, or cell culture test, or antibody test. There is no timing requirement for the laboratory confirmation, i.e. it can be performed also at screening.
4. 4. For patients currently on suppressive therapy, medical history of 3-9 recurrences within the 12 months prior to initiation of suppressive therapy as reported by the patient during screening interview. Suppressive therapy must be discontinued upon screening and at least 14 days prior to the study medication administration.
5. 5. For patients not on suppressive therapy, medical history of 3-9 episodes (with genital lesion) within the last 12 months before screening as reported by the patient during screening interview.
6. 6. If applicable, willingness to discontinue systemic or topical antiviral treatment at screening at least 14 days prior study medication administration.
7. 7. An understanding, ability, and willingness to fully comply with study interventions and restrictions.
8. 8. Ability to provide written, personally signed and dated informed consent to participate in the study, in accordance with the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) Guideline E6 and applicable regulations, before completing any study-related interventions.

Exclusion criteria 20

1. 1. Genital herpes episode presence on Day 1 (applies only at randomization).
2. 2. Medical history or current physical illnesses/medical conditions that constitute an unacceptable risk for study participation in the judgment of the investigator (e.g., clinically significant autoimmune disorder, cancer, active infection, uncontrolled medical conditions or organ system dysfunction that, in the investigator's opinion, could compromise the patient's safety or put the study outcomes at risk, such as uncontrolled hypertension, uncontrolled diabetes mellitus, uncontrolled coronary heart disease, uncontrolled psychiatric condition).
3. 3. Receipt of immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, within the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months).
4. 4. History of any form of ocular HSV infection or HSV- related erythema multiforme.
5. 5. History of drug or alcohol abuse that, in the opinion of the Investigator, would interfere with the patient's ability to comply with the requirements of the study.
6. 6. Any abnormal laboratory value (hematology, biochemistry, serology, urine analysis) of Grade 2 or higher, which is considered as clinically significant by Investigator at screening.
7. 7. Value for ALT and/or AST: ≥ 3 times the upper limit of normal at screening.
8. 8. Value for total bilirubin > upper limit of normal (ULN) x 1.2 at screening, where in case of suspected Gilbert´s disease: total bilirubin ≤ ULN x 3 is acceptable.
9. 9. Value of creatinine clearance: < 60 ml/min (Cockcroft-Gault equation) at screening.
10. 10. Clinically relevant abnormality in the ECG, defined as one or more of the following or other finding based on a medical evaluation of the recording: a) Prolonged QTcF > 450 ms in males and > 470 ms in females; b) Family history of long QT syndrome; c) PR (PQ) interval shortening < 120 ms (PR > 110 ms but < 120 ms is acceptable if there is no evidence of ventricular pre-excitation); d) PR (PQ) interval prolongation (> 240 ms) intermittent second (Wenckebach block while asleep is not exclusive) or third-degree AV block, or AV dissociation; e) e) Persistent or intermittent complete BBB, IBBB, or IVCD with QRS > 110 ms. Patients with QRS > 110 ms but < 115 ms are acceptable if there is no evidence of e.g., ventricular hypertrophy or pre-excitation.
11. 11. Clinically relevant abnormality in vital signs, defined as one or more of the following or other relevant medical evaluation of the measurements: a) Systolic BP < 90 mmHg or > 150 mmHg; b) Diastolic BP < 50 mmHg or > 100 mmHg; c) Body temperature of > 37.7°C (on admission day). Note: Vital signs are measured after 5 minutes rest. Abnormal values may be repeated once at the discretion of Investigator.
12. 12. History of severe allergic or anaphylactic reactions to medications or vaccines.
13. 13. Known allergy / hypersensitivity to additives used in the study drug.
14. 14. Use of another study medication within 30 days prior to receiving the first dose of study medication or enrolment in another drug or vaccine clinical trial.
15. 15. A positive antibody screen for human immunodeficiency virus (HIV), or hepatitis C virus (HCV), or a positive hepatitis B virus surface antigen (HBsAg) test.
16. 16. History of vaccination within 14 days prior to dosing.
17. 17. Pregnancy or lactation.
18. 18. Prior participation in this trial (randomization).
19. 19. Phase 1b part: A positive result in testing for illegal drugs at screening.
20. Prior to randomization: 20. Any relevant intercurrent illness since screening.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. • Rate of HSV shedding, defined as number of days on which genital swab HSV PCR test was positive divided by the total number of days on which genital swabs were obtained in patients receiving different dosing regimens of IM-250 or placebo.

Secondary endpoints 8

1. • Rate of genital lesions, defined as number of days with genital lesions during the 28-day period starting from Day 1 (Phase 1b) or Day 8 (Phase 2a) after the first administration of IM-250 or placebo, divided by 28, in patients receiving different dosing regimens of IM-250 or placebo.
2. • Rate of genital lesions, defined as number of days with genital lesions during the 56-day period starting from Day 1 (Phase 1b) and during 63-day period starting from Day 8 (Phase 2a) after the first administration of IM-250 or placebo, divided by 56 and 63, respectively, in patients receiving different dosing regimens of IM-250 or placebo.
3. • HSV quantity, defined as log10 HSV DNA copies on days that shedding is detected in patients receiving different dosing regimens of IM-250 or placebo.
4. • The rate of subclinical shedding, defined as number of days on which genital swab HSV PCR test was positive in absence of a genital lesion divided by the total number of days without lesions on which genital swabs were obtained in patients receiving different dosing regimens of IM-250 or placebo.
5. Determining the exposure by different doses of IM-250 after single dose (Day 1) as defined by: • the area under the curve from 0 to infinity (AUC0-ꚙ), •maximum observed concentration after single dose (Cmax), •plasma concentration at 24 hours (C24h) and 8 d (C8d), •the area under the curve from 0 to 24 hours (AUC0-24), •the area under the curve from 0 to 168 hours (AUC0-168), •time to reach Cmax (tmax), •half-life (t1/2), •apparent clearance (CL / F), •mean residence time (MRT), •volume of dist
6. • HSV quantity, defined as log10 HSV DNA copies on days that shedding is detected, and genital lesion is detected in patients receiving different dosing regimens of IM-250 or placebo.
7. Determining the exposure by different doses of IM-250 after multiple doses (Day 22) as defined by: • the area under the curve from 0 to infinity (AUC0-ꚙ,ss), • maximum observed concentration at steady state (Cmax,ss), • plasma concentration at 24 hours (C24h,ss) and 8 d (C8d,ss), • the area under the curve from 0 to 24 hours (AUC0-24,ss), • the area under the curve from 0 to 168 hours (AUC0-168,ss), • time to reach Cmax,ss (tmax,ss).
8. Determining the exposure by different dosing regimens of IM-250 after multiple doses (Day 36) as defined by: •the area under the curve from study medication administration to 24 hours post dose at steady state (AUC0-24,ss), •the area under the curve from study drug administration extrapolated to infinity at steady state (AUC0-ꚙ,ss), •maximum observed concentration at steady state (Cmax ,ss), • minimum observed concentration at steady state (Cmin,ss), •apparent clearance at steady state (Cmin,ss

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Innovative Molecules GmbH

Sponsor organisation

Innovative Molecules GmbH

Address

Lipowskystrasse 10, Sendling Sendling

City

Munich

Postcode

81373

Country

Germany

Scientific contact point

Organisation

Innovative Molecules GmbH

Contact name

Company management

Public contact point

Organisation

Innovative Molecules GmbH

Contact name

Company management

Third parties 7

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 37 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

9 submissions — initial application plus substantial / non-substantial modifications