Monoclonal Antibody Therapy Against Chronic Herpes Simplex Virus 2 Infection (MATCH-2)

A Randomized, Double-Blind, Double-Dummy Phase II Study of Single Dose HDIT101 Versus Standard of Care Valaciclovir in Patients With Chronic Recurrent Anogenital HSV-2 Infection

This is a randomized, double-blind, double-dummy study of single dose HDIT101 versus Standard of Care Valaciclovir.

HSV-2-positive patients with at least 4 anogenital herpes lesions in the last 12 months (or at least 2 herpes lesions with previous valaciclovir long-term therapy) can be included.

If a patients develops a anogenital Herpes lesion within 4 months after the screening visit, the patients will be randomized in a 2:1 ratio to HDIT i.v. infusion + episodic treatment with 500 mg Valaciclovir-placebo OR to a single HDIT placebo infusion + episodic treatment with 500 mg Valaciclovir orally bid for 3 days.

Study duration per patient will be 180 days starting with the randomization visit. In addition to the randomization visit, 4 visits at the site and 2 phone calls are scheduled.

At every occurence of a herpetic lesion during the study, patients are treated with Valaciclovir/ Valaciclovir-placebo and need to present at the site twice to document start and end date of the lesion (unscheduled visits).

Study Overview

• Status: Completed
• Conditions: Herpes Genitalis
• Intervention / Treatment: Biological: HDIT101; Drug: Valaciclovir placebo; Drug: Valaciclovir; Biological: HDIT101 placebo

Detailed Description

In this trial, patients with chronic recurrent herpes simplex virus (HSV-2) infections (with at least 4 herpes lesions in the last 12 months or at least 2 herpes lesions with previous valaciclovir long-term therapy) can be included.

After signature of ICF and during the screening period, the patients take daily swabs of the anogenital area for 28 days to determine HSV shedding.

Patients not developing a lesion within 4 months after screening are not randomised. Patients developing a lesion within 4 months can be randomised and the treatment must be initiated within 72 Hours upon lesion occurence.

Approximately 125 patients will be randomized in a 2:1 ratio to one of the following treatment groups:

• Arm A: single HDIT i.v. infusion applied over 1 hour at the randomization visit + episodic treatment with 500 mg Valaciclovir-placebo orally bid for 3 days.
• Arm B: single HDIT placebo i.v. infusion applied over 1 hour at the randomization visit + episodic treatment with 500 mg Valaciclovir orally bid for 3 days.

The HDIT101/HDIT101-placebo infusion is only applied once during the trial, Valaciclovir (or corresponding placebo) has to be taken upon every occurence of another Herpes lesion.

Study duration per Patient will be 180 days starting with the randomization visit. In addition to the randomization visit, 4 visits at the site and 2 phone calls are scheduled.

In case of developing another lesion after the randomization visit, patients take a single swab of the lesion and episodic SoC treatment with Valaciclovir/ Valaciclovir-placebo is started and documented in an electronic diary by the patient within 24 hours after development of first symptoms. Quality of life is also recorded.

In addition to this, the patients need to present at the site within 72 hours after occurence of a the new herpes outbreak for medical examination and to confirm the HSV-2 lesion. At this unscheduled visit at the site, the PI will take a second swab and assess the lesion (including start date). Another unscheduled visit will take place upon healing of lesion.

This procedure will be repeated for every outbreak during the trial.

• Study Type: Interventional
• Enrollment (Actual): 122
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 10629
    • emovis GmbH
  • Berlin, Germany, 10777
    • Praxis Jessen2+Kollegen
  • Bochum, Germany, 44787
    • WIR "Walk In Ruhr" im St. Elisabeth Hospital
  • Frankfurt, Germany, 60596
    • Infektio Research GmbH & Co. KG
  • Freiburg, Germany, 79106
    • Universitätsklinikum Freiburg, Medizin II, Infektiologie
  • Hamburg, Germany, 20146
    • ICH Grindel
  • Koeln, Germany, 50674
    • Dr. Scholten und Schneeweiß GbR
  • Muenchen, Germany, 80336
    • Prinzmed

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age ≥ 18 years at the time of signing informed consent.
2. Signed informed consent for participation in the study.
3. Understanding, ability, and willingness to fully comply with study interventions and restrictions.
4. Seropositive for HSV-2.
5. History of chronic recurrent anogenital HSV-2 infection with ≥ 4 outbreaks (≥ 2 under standard suppressive antiviral therapy) in the last year with no active lesion at time of enrolment. Patients with acute lesion(s) can be enrolled when the previous lesion is healed off.
6. No use of any HSV-suppressant therapy (both approved drugs and non-approved drugs including OTC drugs) including topical applications at least 7 days prior to enrolment.
7. Willingness to not use any topical or systemic anti-HSV therapy (both approved drugs and non-approved drugs including OTC) during the study apart from the study medication.
8. Willingness to not use any topical HSV treatment upon lesion development as well as avoid any manipulation or physical impact, e.g., cooling of the lesion particularly in the prodromal stage.
9. Medical assessment with no clinically significant morbidities or abnormalities as per judgement of the investigator.
10. Women of child-bearing potential (WCBP) must have a negative beta-human chorionic gonadotropin (β-HCG) urine and/or blood test at screening and within 72 hours before receiving study treatment.
11. Willingness to use two independent effective contraceptive methods for 3 months after Visit 1. Male participants and partners of female participants have to use a condom during sexual intercourse or intimacy to reduce the probability of sexually transmitted infection.

Exclusion Criteria:

1. Patients who do not develop a lesion during the 28-day swabbing period and 3 months (90 days) afterwards (i.e., within 4 months after screening).
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, 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. Patients with herpes keratitis.
4. Immunomodulatory therapy including topical (e.g., rectal, vaginal, cutaneous, etc.) and/or oral and/or parenteral and/or inhaling steroids within 28 days before start of study treatment.
5. Any condition that precludes the sampling of up to 200 mL (additional 150 mL in case of optional participation for exploratory objective (T-cell response)) blood over the duration of the study.
6. Known resistance to or intolerance of valaciclovir or active substance or excipients of the study medication.
7. Positive HIV antibody screen, hepatitis B virus (HBV) infection screen, or hepatitis C virus (HCV) antibody screen.
8. Any known history of severe allergic or anaphylactic reactions.
9. Participation in any clinical study within the last 30 days prior to enrolment.
10. Prior participation in this or other clinical study with HDIT101.
11. Pregnant or breast-feeding women.
12. Prior malignant disease except basal cell carcinoma or carcinoma in situ which has been successfully cured more than 5 years before enrolment.
13. Hemoglobin (Hb) < 10 g/dL.
14. Creatinine (Crea) clearance (Cl) < 40 mL/min (Cockcroft-Gault equation will be used)
15. Bilirubin > upper limit of normal (ULN) x 2, except patients with known Morbus Meulengracht.
16. Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) > ULN x 3.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HDIT101 + Valaciclovir placebo; Group A: Patients treated with a single i.v. infusion of 2 g HDIT101 for 60 min at the randomization visit and with an episodic Valaciclovir placebo bid for 3 days.	Biological: HDIT101; i.v. Infusion; Drug: Valaciclovir placebo; oral application of encapsulated Valaciclovir placebo tablets
Active Comparator: HDIT101 placebo + Valaciclovir; Group B: Patients treated with a single i.v. infusion of HDIT101 placebo for 60 min at the randomization visit and with episodic Valaciclovir 500 mg twice daily for 3 days.	Drug: Valaciclovir; oral application of encapsulated Valaciclovir tablets; Other Names: Valtrex; Biological: HDIT101 placebo; i.v. Infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of days with lesion(s) per treatment group	Primary objective is calculated as the number of days with lesion (except the lesion episode at randomization) divided by the number of study days after IMP infusion.	180 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to first recurrence of lesion	Time to first recurrence of lesion as reported by patient and verified by investigator	180 days
Recurrence rate of lesions	Recurrence rate is defined as number of recurrences divided by the total number of study days after IMP infusion	180 days
Duration of recurrent lesions	Duration of recurrent lesions is calculated as consecutive days with lesions of HSV score 2-7	180 days
Disease-specific symptoms	Disease-specific symptoms assessed by Herpes Symptoms Checklist	180 days
Herpes outbreak impact	Herpes outbreak impact assessed by Herpes Outbreak Impact Questionnaire	180 days
QoL	Change in QoL between baseline and EoS assessed by the Recurrent Genital Herpes	180 days

Collaborators and Investigators

• Sponsor: Heidelberg ImmunoTherapeutics GmbH
• Investigators: Study Director: Stefan Schoeffel, Heidelberg ImmunoTherapeutics GmbH

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2019
• Primary Completion (Actual): August 25, 2021
• Study Completion (Actual): November 1, 2021

Study Registration Dates

• First Submitted: November 11, 2019
• First Submitted That Met QC Criteria: November 13, 2019
• First Posted (Actual): November 15, 2019

Study Record Updates

• Last Update Posted (Actual): January 18, 2022
• Last Update Submitted That Met QC Criteria: January 14, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: Herpes Genitalis
• Additional Relevant MeSH Terms: Skin Diseases; Virus Diseases; Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; DNA Virus Infections; Skin Diseases, Infectious; Skin Diseases, Viral; Herpesviridae Infections; Herpes Simplex; Herpes Genitalis; Anti-Infective Agents; Antiviral Agents; Valacyclovir
• Other Study ID Numbers: HTX101-02G

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No