Clinical Trials Register

Summary
EudraCT Number:	2018-003748-22
Sponsor's Protocol Code Number:	MRG106-11-203
National Competent Authority:	Belgium - FPS Health-DGM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2019-04-04
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

Belgium - FPS Health-DGM

A.2

EudraCT number

2018-003748-22

A.3

Full title of the trial

PRISM: An Open-label, Multi-Center Extension Study to Investigate the Efficacy and Safety of Cobomarsen (MRG-106) Following Systemic Treatment in Subjects with Cutaneous T-Cell Lymphoma (CTCL), Mycosis Fungoides (MF) Subtype, Who Have Completed the SOLAR Study

A.3.1

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

PRISM: Efficacy and Safety of Cobomarsen (MRG-106) in Subjects with Mycosis Fungoides, who have completed the SOLAR Study

A.3.2

Name or abbreviated title of the trial where available

PRISM

A.4.1

Sponsor's protocol code number

MRG106-11-203

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	miRagen Therapeutics, Inc.
B.1.3.4	Country	United States
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	miRagen Therapeutics, Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	miRagen Therapeutics, Inc.
B.5.2	Functional name of contact point	SOLAR Clinical Trial Information
B.5.3	Address:
B.5.3.1	Street Address	6200 Lookout Road
B.5.3.2	Town/ city	Boulder
B.5.3.3	Post code	CO 80301
B.5.3.4	Country	United States
B.5.6	E-mail	SOLAR@miragen.com

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	Yes
D.2.5.1	Orphan drug designation number	EU/3/17/1872
D.3 Description of the IMP
D.3.1	Product name	cobomarsen
D.3.2	Product code	MRG-106
D.3.4	Pharmaceutical form	Concentrate for 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	COBOMARSEN
D.3.9.1	CAS number	1848257-52-2
D.3.9.2	Current sponsor code	MRG-106
D.3.9.4	EV Substance Code	SUB192820
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	141
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Cutaneous T-Cell Lymphoma (CTCL), Mycosis Fungoides (MF) Subtype

E.1.1.1

Medical condition in easily understood language

A cancer of the lymphatic system that affects the skin

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10028483
E.1.2	Term	Mycosis fungoides
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective of the trial is to evaluate the efficacy of cobomarsen in subjects with MF who have shown disease progression following treatment with vorinostat in the SOLAR study.

E.2.2

Secondary objectives of the trial

• Investigate the safety and tolerability of cobomarsen in subjects with MF.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Must provide written informed consent (signed and dated), and any authorizations required by law and be able to comply with all study requirements.
2. Must have participated in the comparator arm of the SOLAR clinical trial and completed the study (confirmed disease progression). Subjects who discontinued from SOLAR for any reason other than confirmed disease progression on the comparator arm are not eligible.
3. Meets the following criteria per the central laboratory at Screening:
a. Calculated creatinine clearance ≥ 40 mL/min using 24-hour creatinine clearance OR modified Cockcroft-Gault equation (using ideal body mass [IBM] instead of mass).
b. AST and ALT ≤ 2.5 × the ULN; bilirubin ≤ 1.5 × ULN (except subjects with Gilbert's Syndrome who may have bilirubin ≤ 3.0 × ULN following discussion with the Sponsor).
4. Females who had a menstrual cycle within 2 years of Screening must have a negative serum pregnancy test at Screening and a negative urine pregnancy test on their first dosing day.
5. Subjects of childbearing potential must agree to use highly effective methods of contraception.

E.4

Principal exclusion criteria

Individuals who meet any of the following exclusion criteria are not to be enrolled in this study.
1. Sézary syndrome or mycosis fungoides with B2 involvement, defined as a documented history of B2 and/or B2 staging at the Screening visit. B2 means T-cell clone in peripheral blood + one of the following at Screening:
a. ≥ 1000/μL Sézary cells by direct examination OR
b. ≥ 1000/μL CD4+ CD26- OR
c. ≥ 1000/μL CD4+ CD7-
2. Evidence of large cell transformation.
3. Evidence of visceral involvement related to MF at Screening.
4. Unresolved toxicities from prior vorinostat treatment, defined as having not resolved to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, version 5.0), grade 0 or 1.
5. Receipt of any the following treatments:
• Macrolide or tetracycline antibiotics within 28 days prior to Screening;
• More than 3 short courses of prednisone equivalent > 10 mg per day within 8 weeks prior to Screening; however, a stable regimen of systemic prednisone equivalent to ≤ 10 mg per day (or steroid equivalent) is permitted;
• Any CTCL systemic therapy after completion of the SOLAR study and prior to Day 1 for PRISM.
6. Positive test for blood (including trace) on urinalysis. Subjects with non-clinically significant etiology such as menstrual blood are allowed.
7. An active or uncontrolled infection defined as subjects who require systemic antibacterial, antiviral, or antifungal therapy within the last 7 days prior to Screening.
8. Clinically significant anemia (hemoglobin < 8 g/dL), neutropenia (absolute neutrophil count [ANC] < 1000/mm3) or thrombocytopenia (platelets < 50,000/mm3) at Screening.
9. Presence on ECG of QT interval corrected for heart rate using Fridericia's formula (QTcF) > 450 msec for males or > 470 msec for females or > 480 msec for subjects with bundle branch block, based on a mean of the triplicate ECG measurements collected at Screening.
10. Unwillingness to comply with study procedures, including follow-up, as specified by this protocol, or inability to communicate or cooperate fully with the Investigator.
11. Lactating or pregnant.
12. Major surgery within 4 weeks of the first dose of study treatment.
13. Any active, clinically significant, unresolved adverse event (related or unrelated to study drug) from the prior study at the time of Screening.
14. Unable to understand the purpose and risks of the study and to provide a signed and dated informed consent form (ICF) and authorization to use protected health information (in accordance with national and local subject privacy regulations).
15. Clinically significant abnormalities in medical history, physical examination, or laboratory values that, in the opinion of the Investigator, would make the subject unsuitable for inclusion in the study.

E.5 End points

E.5.1

Primary end point(s)

Primary Efficacy Evaluation:
• Proportion of subjects achieving an objective response (complete response [CR] or partial response [PR]) of at least 4 months duration (ORR4) using composite global response criteria, including radiological imaging, flow cytometry, and the mSWAT scoring.

E.5.1.1

Timepoint(s) of evaluation of this end point

Global response criteria collected 4 weeks after 4 months of sustained response (PR or CR) in the skin, and every 12 weeks thereafter.

E.5.2

Secondary end point(s)

Efficacy measures:
• Key Secondary Endpoint: Progression-free survival (PFS).
• Change from baseline and longitudinally during the study in Pruritus Numerical Rating Scale (NRS).
• Change from baseline and longitudinally during the study in Skindex-29 total score.
• Change from baseline and longitudinally during the study in Skindex-29 Subdomains (Symptoms, Emotion and Functionality).
• Change from baseline and longitudinally during the study in Pain NRS.
• Difference in drug tolerability by Patient Impression of Treatment Side Effects
• Duration of composite global response for responding subjects.
• Complete response rate (CRR).
• Time to progression (TTP).
• Time to maximal effect in mSWAT.
• Proportion of subjects achieving ≥ 50% improvement in mSWAT of at least 4 months duration.
• Proportion of subjects achieving ≥ 50% improvement in mSWAT of at least 28 days in duration.
• Percent of subjects achieving ≥ 50% improvement in mSWAT from baseline at 28 days and at 4 months.
• Time to ≥ 50% improvement in mSWAT.
• Duration of response in skin (no progression after achieving ≥ 50% improvement in mSWAT).
• Change in pruritus medication utilization from baseline and incidence of pruritus medication utilization.
• Overall survival.
• Time to next treatment

Safety and Tolerability Evaluations:
• Incidence and severity of clinically significant AEs (including grade 3 and 4 AEs, treatment-related AEs, SAEs, and AEs requiring discontinuation), physical examination findings, changes in
electrocardiogram (ECGs), changes in laboratory parameters and changes in vital signs.

Pharmacokinetic Evaluation:
• Pharmacokinetic Cmax and trough concentration analysis

E.5.2.1

Timepoint(s) of evaluation of this end point

Progression free survival, time to progression, overall survival, complete
response rate: assessed throughout study
Daily pruritus and pain score, patient impression of treatment side
effects: from Day 1 until follow up visit.
Skindex-29, mSWAT: every 4 weeks to week 81, every 8 weeks
thereafter
Safety and tolerability: assessed throughout study
PK: Days 1, 2, 3, 5, 8, 15, 29, every 4 weeks through week 81 and every
8 weeks thereafter.

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

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

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

E.8.1.1

Randomised

Information not present in EudraCT

E.8.1.2

Open

Information not present in EudraCT

E.8.1.3

Single blind

Information not present in EudraCT

E.8.1.4

Double blind

Information not present in EudraCT

E.8.1.5

Parallel group

Information not present in EudraCT

E.8.1.6

Cross over

Information not present in EudraCT

E.8.1.7

Other

Information not present in EudraCT

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Information not present in EudraCT

E.8.2.2

Placebo

Information not present in EudraCT

E.8.2.3

Other

Information not present in EudraCT

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Australia

Austria

Belgium

Canada

France

Germany

Italy

Netherlands

Spain

United Kingdom

United States

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

LVLS

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:

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

Information not present in EudraCT

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

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)

None

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

2019-04-25

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-07-26

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2020-07-27

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