Clinical Trials Register

Summary
EudraCT Number:	2014-005623-27
Sponsor's Protocol Code Number:	RM-131-009
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:	2015-04-07
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

2014-005623-27

A.3

Full title of the trial

A Phase 2b, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety and Efficacy of RM-131 Administered to Patients with Vomiting Symptoms and Moderate to Severe Diabetic Gastroparesis

A.3.1

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

A controlled clinical trial to study RM-131 (relamorelin) in patients with vomiting symptoms and diabetic gastroparesis

A.4.1

Sponsor's protocol code number

RM-131-009

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	Rhythm Pharmaceuticals, 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	Rhythm Pharmaceuticals, 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	Rhythm Pharmaceuticals, Inc.
B.5.2	Functional name of contact point	Information
B.5.3	Address:
B.5.3.1	Street Address	855 Boylston Street
B.5.3.2	Town/ city	Boston
B.5.3.3	Post code	MA 02116
B.5.3.4	Country	United States
B.5.4	Telephone number	+18572644280
B.5.5	Fax number	+18572644299
B.5.6	E-mail	ffiedorek@rhythmtx.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	Relamorelin
D.3.2	Product code	RM-131
D.3.4	Pharmaceutical form	Solution for injection in pre-filled syringe
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	None
D.3.9.1	CAS number	945416-05-7
D.3.9.2	Current sponsor code	RM-131
D.3.9.3	Other descriptive name	RELAMORELIN
D.3.9.4	EV Substance Code	SUB171935
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
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.IMP: 2
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	Relamorelin
D.3.2	Product code	RM-131
D.3.4	Pharmaceutical form	Solution for injection in pre-filled syringe
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	None
D.3.9.1	CAS number	945416-05-7
D.3.9.2	Current sponsor code	RM-131
D.3.9.3	Other descriptive name	RELAMORELIN
D.3.9.4	EV Substance Code	SUB171935
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	30
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.IMP: 3
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	Relamorelin
D.3.2	Product code	RM-131
D.3.4	Pharmaceutical form	Solution for injection in pre-filled syringe
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	None
D.3.9.1	CAS number	945416-05-7
D.3.9.2	Current sponsor code	RM-131
D.3.9.3	Other descriptive name	RELAMORELIN
D.3.9.4	EV Substance Code	SUB171935
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(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	Solution for injection in pre-filled syringe
D.8.4	Route of administration of the placebo	Subcutaneous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Vomiting symptoms in patient with moderate to severe diabetic gastroparesis

E.1.1.1

Medical condition in easily understood language

Vomiting symptoms in patient with moderate to severe diabetic gastroparesis

E.1.1.2

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	17.1
E.1.2	Level	PT
E.1.2	Classification code	10051153
E.1.2	Term	Diabetic gastroparesis
E.1.2	System Organ Class	10017947 - Gastrointestinal disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

• Evaluate the effect of RM-131 on vomiting episodes in patients with diabetic gastroparesis (DG).

E.2.2

Secondary objectives of the trial

• Evaluate the effects of RM-131 on 4 key symptoms of gastroparesis (nausea, early satiety, bloating, and abdominal pain) assessed with a composite score derived from the Diabetic Gastroparesis Symptom Severity Diary (DGSSD).
• Evaluate the effect of RM-131 on vomiting severity (as assessed in the DGSSD).
• Evaluate the effect of RM-131 on gastric emptying (GE).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. T1DM or T2DM with stable glycemic control and HbA1c ≤11% at screening.
2. DG, defined as at least a 3-month history of symptoms suggestive of gastroparesis on an ongoing basis (e.g., vomiting, nausea, early satiety, bloating, or epigastric or abdominal pain).
3. GCSI-DD score ≥2.6 at least once during the Screening Period (Visits 1-2).
4. At least 2 vomiting episodes during the ~2 weeks prior to the first screening visit (Visit 1), as ascertained by patient history.
5. Delayed GE confirmed at screening by abnormal GEBT (AB Diagnostics), defined as GE half-time (t1/2) ≥79 minutes (the 80th percentile of normative data). At least 50% of patients enrolled will have a t1/2 ≥97 minutes (i.e., the 95th percentile).
6. Stable concomitant medications, defined as no changes in regimen for at least 2 weeks prior to Visit 2 (daily adjustments of insulin doses are permitted).
7. No use of metoclopramide, erythromycin, domperidone, or other GI motility agents, or anti-emetics for at least 2 weeks prior to Visit 2, and willingness to remain off these medications (except as used as part of protocol specific rescue medication) during the course of the clinical trial.
8. Body mass index >18 kg/m2.
9. If female, has a negative serum or urine pregnancy test and is not lactating. For females able to bear children, a hormonal (i.e., oral, implantable, or injectable) and single-barrier method, or a double-barrier method of birth control must be used throughout the study. Female patients unable to bear children must have this documented in the eCRF (i.e., tubal ligation, hysterectomy, or post-menopausal [defined as a minimum of 1 year since
the last menstrual period]). Post-menopausal status will be confirmed by measurement of follicle stimulating hormone (FSH).
10. Able to provide written informed consent prior to any study procedures and willing and able to comply with study procedures.

Additional inclusion criteria for randomization after the 2-week single-blind placebo run-in period:
11. Compliance with the completion of the DGSSD and study drug injections, defined as approximately 80% diary completions and approximately 80% administration of injections, during the 2-week single-blind placebo run-in period. For those patients whose compliance is measured to be <80%, the final decision to randomize a patient will be made by the Investigator and the Sponsor (or designee).
12. At least one vomiting episode at any time during the 2-week single-blind placebo run-in period, as recorded in the DGSSD.

E.4

Principal exclusion criteria

1. Currently receiving parenteral feeding or presence of a nasogastric or other enteral tube for feeding or decompression.
2. History of gastric surgery such as fundoplication, gastrectomy, gastric pacemaker placement, vagotomy, or bariatric procedure. (A history of diagnostic endoscopy is not exclusionary.)
3. History of pyloric injection of botulinum toxin within 6 months of screening.
4. Patients with clinical suspicion of upper GI obstruction (e.g., peptic stricture) must have been evaluated per standard of care and obstruction ruled out before screening.
5. Currently taking opiates, or expecting to use opiates during the course of the clinical trial.
6. Currently taking GLP-1 agonists, SGLT2 inhibitors or pramlintide.
7. Allergic or intolerant of egg, wheat, milk, or algae, as these are components of the GEBT study meal. (Gluten-free crackers can be provided.)
8. History of anorexia nervosa, binge-eating, or bulimia within 5 years of screening.
9. ALT or AST > 2 × upper limit of normal (ULN) at Visit 1.
10. History of intestinal malabsorption or pancreatic exocrine disease.
11. Requires hemodialysis or has end-stage renal disease.
12. History of human immunodeficiency virus (HIV) infection.
13. Clinically significant neurologic or psychiatric disorders that are likely to impact compliance with protocol requirements.
14. Poor venous access or inability to tolerate venipuncture.
15. Participation in a clinical study within the 30 days prior to dosing in the present study.
16. Any other reason that, in the Investigator’s opinion, would confound proper interpretation of the study or expose a patient to unacceptable risk, including renal, hepatic or cardiopulmonary disease, or significant acute ECG abnormalities.

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy endpoint is:
• Longitudinal analysis of the number of weekly vomiting episodes, averaged across the 12-week treatment period.

E.5.1.1

Timepoint(s) of evaluation of this end point

Weekly

E.5.2

Secondary end point(s)

The key secondary efficacy endpoint is:
• Longitudinal analysis of changes from baseline over time in weekly averages of the 4 individual daily symptom scores (e.g., the 4 subjective symptoms) using a global statistic.
Secondary efficacy endpoints are:
• Longitudinal analysis of changes from baseline over time in weekly average of the 4- symptom composite of subjective symptoms of DG (nausea, early satiety, bloating, and epigastric or abdominal pain).
• Longitudinal analysis of weekly average vomiting episodes.
• Longitudinal analysis of changes from baseline over time in weekly averages of the other individual daily symptom scores (e.g., the 4 subjective symptoms).
• Longitudinal analysis of changes from baseline over time in weekly averages of vomiting severity.
• Longitudinal analysis of changes from baseline over time in weekly averages of the 5 individual daily symptom scores (e.g., the 4 subjective symptoms and vomiting endpoints) using a global statistic.
• Gastric emptying as measured by the GEBT half-time.

Other tertiary and exploratory endpoints will include PK, PK/PD, weight, glucose, and analysis of different global statistical approaches. Effects of RM-131 on symptoms of gastroparesis will be evaluated using the DGSSD. Exploratory assessments of symptoms may also utilize Symptom and Global Assessment data.

Safety endpoints include:
• Physical examination, including assessment of the injection site, weight and vital signs
• Clinical laboratory safety tests:
• Complete blood count (CBC) with automated differential
• Chemistry panel (including sodium, potassium, chloride, carbon dioxide (CO2), albumin, glucose, calcium, total protein, aspartate aminotransferase (AST), ALT, GGT, creatine kinase (CK), alkaline phosphatase, total bilirubin, direct bilirubin, blood urea nitrogen (BUN), creatinine, uric acid, lactate dehydrogenase (LDH), cholesterol and triglycerides. (Procedures for follow-up of abnormal liver function tests are provided in Appendix 11.6.)
• Urinalysis (microscopic review if indicated)
• HbA1c
• AE review
• Concomitant medication review
• ECG evaluations
• Anti-RM-131 antibody measurements
• IGF-1 and prolactin levels

E.5.2.1

Timepoint(s) of evaluation of this end point

Weekly

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

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

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

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

Belgium

Germany

Israel

Poland

Sweden

United Kingdom

United States

E.8.7

Trial has a data monitoring committee

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

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:

265

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

100

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

395

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)

Standard of care.

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

2015-05-20

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-06-10

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2016-06-09

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