Clinical Trials Register

Summary
EudraCT Number:	2014-004113-85
Sponsor's Protocol Code Number:	PA101-SM-02
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2014-12-11
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 - BfArM

A.2

EudraCT number

2014-004113-85

A.3

Full title of the trial

Randomized, Double-blind, Placebo-controlled, Crossover Design, Efficacy and Safety Study with PA101 in Patients with Indolent Systemic Mastocytosis

A.3.1

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

A controlled study in patients with Indolent Systemic Mastocytosis to determine the safety and efficacy of PA101 when compared with an existing drug and a placebo

A.4.1

Sponsor's protocol code number

PA101-SM-02

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	Patara Pharma, LLC
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	Patara Pharma, LLC
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	Premier Research
B.5.2	Functional name of contact point	Project Manager
B.5.3	Address:
B.5.3.1	Street Address	Center Square, West Tower, 1500 Market Street
B.5.3.2	Town/ city	Philadelphia
B.5.3.3	Post code	PA 19102
B.5.3.4	Country	United States
B.5.4	Telephone number	++12154469288
B.5.5	Fax number	++12152825528
B.5.6	E-mail	joan.sutphen-glowatz@premier-research.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	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Disodium Cromoglycate
D.3.2	Product code	PA101
D.3.4	Pharmaceutical form	Nebuliser solution
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Inhalation use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	SODIUM CROMOGLICATE
D.3.9.1	CAS number	15826-37-6
D.3.9.2	Current sponsor code	PA101
D.3.9.4	EV Substance Code	SUB12286MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	not less then
D.3.10.3	Concentration number	40
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	Yes
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.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	Nalcrom
D.2.1.1.2	Name of the Marketing Authorisation holder	Sanofi
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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	Nalcrom
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	SODIUM CROMOGLICATE
D.3.9.1	CAS number	15826-37-6
D.3.9.4	EV Substance Code	SUB12286MIG
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	100
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	Inhalation solution
D.8.4	Route of administration of the placebo	Inhalation use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Indolent Systemic Mastocytosis

E.1.1.1

Medical condition in easily understood language

Mastocytosis is a rare condition caused by an excess number of mast cells gathering in the body's tissues. In systemic mastocytosis, mast cells gather in tissues such as the skin, organs and bones.

E.1.1.2

Therapeutic area

Diseases [C] - Blood and lymphatic diseases [C15]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	18.1
E.1.2	Level	PT
E.1.2	Classification code	10042949
E.1.2	Term	Systemic mastocytosis
E.1.2	System Organ Class	10005329 - Blood and lymphatic system disorders

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

To determine the efficacy profile of PA101 delivered via a high efficiency nebulizer (eFlow®, PARI) in comparison with placebo following 6 weeks of treatment in patients with indolent systemic mastocytosis (ISM) who are symptomatic despite using standard treatments

E.2.2

Secondary objectives of the trial

To compare the efficacy and safety profile of PA101 to marketed oral cromolyn sodium (open-label control);
To assess the safety, tolerability, and pharmacokinetic (PK) profile of PA101

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

Protocol AMD 3.1, 02Jul15:
Skin assessments and skin biopsy at select treatment visits (i.e. V1 and V5) at each treatment period.
These assessments will include provocation of Darier's sign (wheal and erythema reaction, itching and burning sensation), and skin biopsy (number of mast cells, and immunohistochemical staining for biomarkers).

Secondary efficacy measurements:
- Change from baseline in skin reaction (wheal and erythema reaction, itching and burning sensation)
- Change from baseline in skin mast cell burden (number of mast cells and biomarkers)

E.3

Principal inclusion criteria

1. Male or female patients 18-75 years of age, inclusive
2. Diagnosed with indolent systemic mastocytosis (ISM) according to the WHO criteria and the consensus proposal (2001)
3. Experiencing at least one qualifying symptom in at least two organ systems during the 3 months preceding the Screening Visit, despite the use of H1 and/or H2 antihistamines and/or other antimediator therapy
4. Experiencing symptoms with a severity score of at least 4 for at least 7 out of 14 days during the Run-in Period with at least one qualifying symptom each from at least two organ systems, despite the use of H1 and/or H2 antihistamines and/or other anti-mediator therapy
5. Willing and able to use an eDiary device daily for the duration of the study
6. Completed at least 5 eDiary reports during each of two consecutive weeks of the Run-in Period
7. Patients must digitally accept the licensing agreement in the eDiary software
8. Willingness and ability to provide written informed consent prior to any study procedures performed

E.4

Principal exclusion criteria

1. Advanced systemic mastocytosis (i.e., aggressive systemic mastocytosis [ASM], mast cell leukemia [MCL], or systemic mastocytosis with an associated clonal hematologic non-mast cell lineage disease [SM-AHNMD] )
2. Current or recent history of clinically significant cardiovascular, hematological, renal, neurologic, hepatic, endocrine, psychiatric, malignant, or other illnesses that could put the patient at risk or compromise the quality of the study data as determined by the Investigator
3. Use of oral cromolyn sodium within 6 weeks of the Screening Visit
4. History of systemic corticosteroid use within 6 weeks, or immunosuppressive, or anti-IgE monoclonal antibody therapy (e.g., omalizumab) within 6 months of the Screening Visit
5. History of anaphylaxis requiring systemic treatment (i.e., corticosteroid or epinephrine) within 12 months of the Screening Visit
6. An upper or lower respiratory tract infection within 4 weeks of the Screening Visit
7. History of malignancy within the last 5 years, except basal cell carcinoma or cervix carcinoma in situ
8. Major surgery within 6 months of the Screening Visit
9. History of excessive use or abuse of alcohol (i.e., more than 3 units per day, or more than 21 units per week) within 12 months of the Screening Visit
10. History of abusing legal drugs or use of illegal drugs or substances within 12 months of the Screening Visit
11.Females who are pregnant or breastfeeding, or if of child-bearing potential unwilling to practice acceptable means of birth control or abstinence during the study; females of child-bearing potential must use one reliable method of contraception (i.e., Pearl Index of less than 1%)
12.Participation in any other investigational drug study within 4 weeks of the Screening Visit
13.History of hypersensitivity or intolerance to aerosol medications or cromolyn sodium
14.Patients under guardianship, trusteeship, or committed to an institution by order of government or judicial authorities
15.Patients who have a relationship as such that they are rendered dependent to the investigator/study site staff, or the sponsor

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy endpoint is change from baseline in total symptom score recorded in the daily eDiary using the MAS Plus questionnaire at Week 6.

E.5.1.1

Timepoint(s) of evaluation of this end point

Week 6

E.5.2

Secondary end point(s)

Secondary efficacy endpoints include the
- changes from baseline in each organ system domain and in each symptom score using the MAS Plus questionnaire
- change from baseline in quality of life as measured using the MIQ and SF-36 Questionnaire at Week 6.
- PGIC score
In the patients being assessed for provocation of Darier's sign, change from baseline in skin reactions and mast cell burden will also be assessed.

E.5.2.1

Timepoint(s) of evaluation of this end point

Week 6

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

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

E.8.1.6

Cross over

Yes

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

Yes

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

Nalcrom® 100 mg oral capsules

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

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

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

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 months

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

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

2015-03-11

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-03-18

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2016-06-22

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