Clinical Trials Register

Summary
EudraCT Number:	2019-000880-26
Sponsor's Protocol Code Number:	HTX101-02G
National Competent Authority:	Germany - PEI
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2019-05-16
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Germany - PEI

A.2

EudraCT number

2019-000880-26

A.3

Full title of the trial

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

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Monoclonal Antibody Therapy against Chronic Herpes Simplex Virus 2 infection

A.3.2

Name or abbreviated title of the trial where available

MATCH-2

A.4.1

Sponsor's protocol code number

HTX101-02G

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Heidelberg ImmunoTherapeutics GmbH
B.1.3.4	Country	Germany
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Heidelberg ImmunoTherapeutics GmbH
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Heidelberg ImmunoTherapeutics GmbH
B.5.2	Functional name of contact point	Stefan Schöffel
B.5.3	Address:
B.5.3.1	Street Address	Max-Jarecki-Str. 21
B.5.3.2	Town/ city	Heidelberg
B.5.3.3	Post code	69115
B.5.3.4	Country	Germany
B.5.4	Telephone number	+496221391938
B.5.5	Fax number	+4962216722299
B.5.6	E-mail	stefan.schoeffel@hditx.de

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	HDIT101
D.3.4	Pharmaceutical form	Solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Not available
D.3.9.2	Current sponsor code	HDIT101
D.3.9.3	Other descriptive name	HUMANIZED IgG1 KAPPA MONOCLONAL ANTIBODY
D.3.9.4	EV Substance Code	SUB33338
D.3.10	Strength
D.3.10.1	Concentration unit	g gram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	2
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Valtrex®
D.2.1.1.2	Name of the Marketing Authorisation holder	GlaxoSmithKline GmbH & Co. KG
D.2.1.2	Country which granted the Marketing Authorisation	Germany
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Valtrex®
D.3.4	Pharmaceutical form	Capsule
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Valaciclovir
D.3.9.1	CAS number	124832-27-5
D.3.9.3	Other descriptive name	VALACICLOVIR HYDROCHLORIDE
D.3.9.4	EV Substance Code	SUB15679MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	500
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for infusion
D.8.4	Route of administration of the placebo	Intravenous use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Chronic recurrent anogenital HSV-2 infection

E.1.1.1

Medical condition in easily understood language

Herpes genitalis

E.1.1.2

Therapeutic area

Diseases [C] - Virus Diseases [C02]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10019938
E.1.2	Term	Herpes genitalis
E.1.2	System Organ Class	100000004862

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To assess the efficacy of single dose of HDIT101 versus episodic SoC treatment with valaciclovir in patients with chronic recurrent anogenital HSV-2 infection as measured by the percentage of days with lesion(s) during the study (calculated as number of days with lesion, except the lesion episode at randomization, divided by the number of days in the study after IMP infusion).

E.2.2

Secondary objectives of the trial

Key secondary objectives of the study are to compare the efficacy of single dose of HDIT101 versus episodic SoC treatment with valaciclovir with respect to:
• Time after IMP infusion to first recurrence of lesion(s)
• Recurrence rate
• Duration of lesion(s)
• Disease-specific symptoms
• Herpes outbreak impact on daily life
• Patient’s QoL
Other study secondary objectives are:
• To compare safety and tolerability between the two treatment groups
• To compare HSV-2 copy numbers from HSV DNA positive samples (swabs) between the two treatment groups
• To assess the immunogenicity of HDIT101 (anti-drug antibodies [ADA])
• To determine the PK profile of HDIT101 in patients with HSV-2 infection.

E.2.3

Trial contains a sub-study

E.3

Principal 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. Previous serology laboratory reports (no PCR) provided by the patient are acceptable.
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 during trial participation and at least 7 days prior to start of first 28 days swabbing period and/or treatment.
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. Topical anti-HSV therapy of orolabial lesions is allowed.
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.

E.4

Principal 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) except patients who have reported lesions to the investigator within this screening period but were not able to be randomized due to timely restrictions (e.g. COVID-19 travel restrictions, holidays, vacation etc.). Those patients can still be randomized after additional 30 days (150 days in total).
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) infection 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 treatment with HDIT101 in this or other clinical study .
11. Pregnant or breast-feeding women.
12. Prior malignant disease (except basal cell carcinoma or carcinoma in situ) which has not been successfully cured more than 5 years before enrolment.
13. Hemoglobin (Hb) < 10 g/dL.
14. Creatinine (Crea) clearance (Cl) < 40 mL/min (Cockroft-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.

E.5 End points

E.5.1

Primary end point(s)

Percentage of days with lesion(s) per treatment group, except the lesion episode at randomization, calculated as the number of days with lesion divided by the number of study days after IMP infusion. A lesion is defined as presence of lesion with HSV lesion score 2-7.

E.5.1.1

Timepoint(s) of evaluation of this end point

Visit 1 and Unscheduled visit in case of new lesion (and if applicable on the following days until lesion healing)

E.5.2

Secondary end point(s)

Key Secondary Endpoints:
• Time to first recurrence of lesion (HSV lesion score 2-7) reported by the patient and verified by the investigator
• Recurrence rate of lesions (defined as number of recurrences divided by the total number of study days after IMP infusion).
• Duration of recurrent lesions (calculated as consecutive days with lesions of HSV score 2-7).
• Disease-specific symptoms assessed by Herpes Symptom Checklist (HSC) questionnaire.
• Herpes outbreak impact assessed by Herpes Outbreak Impact Questionnaire (HOIQ).
• Change in QoL between baseline and EoS assessed by the Recurrent Genital Herpes QoL (RGHQoL) questionnaire.
Other Secondary Endpoints:
• Safety and tolerability of HDIT101 versus SoC based on incidence, severity and relationship of treatment-related AEs and SAEs, laboratory tests, vital signs and electrocardiogram (ECG).
• HSV copy numbers from HSV DNA positive swabs.
• ADA
• Non-compartmental PK characteristics of HDIT101
• Population PK evaluation.

E.5.2.1

Timepoint(s) of evaluation of this end point

Visit (V) 1 and unscheduled visit in case of new lesion; From first to last day of symptoms; Herpes Symptom Checklist (HSC) questionnaire and Herpes Outbreak Impact Questionnaire (HOIQ): V1 and unscheduled visit in case of new lesion; from first to last day of symptoms; Recurrent Genital Herpes QoL (RGHQoL) questionnaire: V1 and V7; AEs/SAEs: every visit; laboratory tests: V1, V2, V4, V6 and V7; vital signs: V1, V2, V4, V6 and V7; ECG: V1 and V7; Swabs: Screening +28 days, V1 +28 days, V6 +28 days, unscheduled Visit +28 days in case of new lesion; ADA: V1, V2, V4, V6, V7 and unscheduled Visit in case of new lesion (if prior to Day 15 (V2), no ADA sample); PK: V1, V2, V4, V6, V7 and unscheduled Visit in case of new lesion

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Double dummy

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

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

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

Yes

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

The end of study is defined as last patient across all sites has completed last visit (LPLV)

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

105

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

125

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

After a patient has ceased his/her participation in the study, his/her medical doctor will offer the most appropriate treatment currently available

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2019-08-06

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-09-03

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2021-08-25

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