First in Human Single Ascending Dose Study of MOR107

Assessment of Safety, Tolerability and Pharmacokinetics of Single Ascending Subcutaneous Doses of MOR107 in Healthy Male Subjects and Pharmacodynamics in Healthy Male Subjects on a Low Sodium Diet

This is the first in human study of MOR107. It is a 2 part, single centre, double-blind, randomised, placebo-controlled study in healthy male subjects. Part 1 is a single ascending dose study, and Part 2 is a parallel group, dose range finding study in healthy male subjects on a low sodium diet.

Study Overview

• Status: Terminated
• Conditions: Safety
• Intervention / Treatment: Drug: MOR107; Drug: Placebo; Other: Low sodium diet

Detailed Description

MOR107 is an angiotensin 2 receptor (AT2R) agonist with the potential to treat a wide range of diseases through activation of the protective arm of the renin-angiotensin system.

In this study MOR107 will be administered to humans for the first time.

The study will enroll healthy male subjects and is split into two sequential parts, both of which have a single centre, double-blind, randomised, placebo-controlled design.

Part 1 will evaluate the safety, tolerability and pharmacokinetics (PK) of single ascending doses of MOR107.

Part 2 will evaluate the pharmacodynamics, safety, tolerability and PK of three different doses of MOR107 in healthy male subjects who will be fed a low sodium diet in order to increase AT2R expression.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Nottinghamshire
    • Nottingham, Nottinghamshire, United Kingdom, NG11 6JS
      • Quotient Clinical

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Key Inclusion Criteria:

1. Healthy males
2. Age 18 to 45 years of age
3. Body mass index of 18.0 to 32.0 kg/m2
4. For Part 2, subjects must have at least a 25% reduction in 24 hour urinary sodium excretion on Day -2 compared with admission

Key Exclusion Criteria:

1. Subjects who have received any IMP in a clinical research study within the previous three months
2. Regular alcohol consumption >21 units per week (1 unit = ½ pint beer, 25 mL of 40% spirit or a 125 mL glass of wine)
3. Current smokers and those who have smoked within the last 12 months. A breath carbon monoxide reading of greater than 10 ppm at screening/admission
4. Current smokers of e-cigarettes and nicotine replacement products and those who have smoked these products within the last 12 months
5. Clinically significant abnormal biochemistry, haematology or urinalysis as judged by the investigator
6. Positive drugs of abuse test result
7. Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) results
8. History of psychiatric disorder, cardiovascular, renal, hepatic, chronic respiratory or gastrointestinal disease as judged by the investigator
9. Serious adverse reaction or serious hypersensitivity to any drug or the formulation excipients

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

11

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1, MOR107 Dose level 1; MOR107, single subcutaneous injection	Drug: MOR107; MOR107 solution for injection; Other Names: LP2-3
Experimental: Part 1, MOR107 Dose level 2; MOR107, single subcutaneous injection	Drug: MOR107; MOR107 solution for injection; Other Names: LP2-3
Experimental: Part 1, MOR107 Dose level 3; MOR107, single subcutaneous injection	Drug: MOR107; MOR107 solution for injection; Other Names: LP2-3
Experimental: Part 1, MOR107 Dose level 4; MOR107, single subcutaneous injection	Drug: MOR107; MOR107 solution for injection; Other Names: LP2-3
Experimental: Part 1, MOR107 Dose level 5; MOR107, single subcutaneous injection	Drug: MOR107; MOR107 solution for injection; Other Names: LP2-3
Experimental: Part 1, MOR107 Dose level 6; MOR107, single subcutaneous injection	Drug: MOR107; MOR107 solution for injection; Other Names: LP2-3
Placebo Comparator: Part 1, Placebo; Placebo, single subcutaneous injection	Drug: Placebo; Solution for injection manufactured to match MOR107 solution for injection; Other Names: Placebo (for MOR107)
Experimental: Part 2: MOR107 low dose; MOR107 low dose single subcutaneous injection and low sodium diet for 6 days before dosing and 2 days after dosing	Drug: MOR107; MOR107 solution for injection; Other Names: LP2-3; Other: Low sodium diet; Diet designed to restrict sodium intake to 40 mmol/day
Experimental: Part 2: MOR107 medium dose; MOR107 medium dose single subcutaneous injection and low sodium diet for 6 days before dosing and 2 days after dosing	Drug: MOR107; MOR107 solution for injection; Other Names: LP2-3; Other: Low sodium diet; Diet designed to restrict sodium intake to 40 mmol/day
Experimental: Part 2: MOR107 high dose; MOR107 high dose single subcutaneous injection and low sodium diet for 6 days before dosing and 2 days after dosing	Drug: MOR107; MOR107 solution for injection; Other Names: LP2-3; Other: Low sodium diet; Diet designed to restrict sodium intake to 40 mmol/day
Placebo Comparator: Part 2: Placebo; Placebo single subcutaneous injection and low sodium diet for 6 days before dosing and 2 days after dosing	Drug: Placebo; Solution for injection manufactured to match MOR107 solution for injection; Other Names: Placebo (for MOR107); Other: Low sodium diet; Diet designed to restrict sodium intake to 40 mmol/day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of treatment-emergent adverse events (safety and tolerability)	Reporting of adverse events, physical examination, injection site assessment, vital signs, ECG, and clinical chemistry, haematology and urinalysis	Up to 10 days post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time from dosing at which the maximum MOR107 concentration was observed (Tmax)	Plasma PK parameter	Up to 48 hours post-dose
Maximum observed MOR107 concentration (Cmax)	Plasma PK parameter	Up to 48 hours post-dose
Concentration of MOR107 at 12 hours post-dose (C12)	Plasma PK parameter	12 hours post-dose
Concentration of MOR107 at 24 hours post-dose (C24)	Plasma PK parameter	24 hours post-dose
Area under the curve from 0 time to last measurable MOR107 concentration (AUC0-t)	Plasma PK parameter	Up to 48 hours post-dose
Area under the curve from 0 time to infinity for MOR107 (AUC0-inf)	Plasma PK parameter	Up to 48 hours post-dose
Percentage of AUC(0-inf) for MOR107 extrapolated beyond last measured time point (AUC%extrap)	Plasma PK parameter	Up to 48 hours post-dose
Slope of the apparent elimination phase for MOR107 (Lambda-z)	Plasma PK parameter	Up to 48 hours post-dose
Apparent elimination half-life for MOR107 (T-half)	Plasma PK parameter	Up 48 hours post-dose
MOR107 Cmax normalised for dose (Cmax/D)	Plasma PK parameter	Up to 48 hours post-dose
MOR107 AUC(0-t) normalised for dose (AUC[0-t]/D)	Plasma PK parameter	Up to 48 hours post-dose
MOR107 AUC(0-inf) normalised for dose (AUC[0-inf]/D)	Plasma PK parameter	Up to 48 hours post-dose
Amount of MOR107 excreted in the urine over a specified period of time after dosing (Ae)	Urine PK parameter	Up to 48 hours post-dose
Cumulative amount of MOR107 excreted in the urine (CumAe)	Urine PK parameter	Up to 48 hours post-dose
Amount of MOR107 excreted in the urine over a specified period of time after dosing, expressed as a percentage of the administered dose (Ae%)	Urine PK parameter	Up to 48 hours post-dose
Cumulative amount of MOR107 excreted in the urine, expressed as a percentage of the administered dose (CumAe%)	Urine PK parameter	Up to 48 hours post-dose
Renal clearance: the apparent volume of plasma cleared per unit time via renal elimination (CLr)	Urine PK parameter	Up to 48 hours post-dose

Collaborators and Investigators

• Sponsor: Alan Richardson
• Collaborators: Quotient Clinical
• Investigators: Study Director: Axel Mescheder, MD, LanthioPep BV

Study record dates

Study Major Dates

• Study Start (Actual): February 16, 2017
• Primary Completion (Actual): March 23, 2017
• Study Completion (Actual): March 23, 2017

Study Registration Dates

• First Submitted: February 21, 2017
• First Submitted That Met QC Criteria: February 24, 2017
• First Posted (Actual): March 1, 2017

Study Record Updates

• Last Update Posted (Actual): February 7, 2018
• Last Update Submitted That Met QC Criteria: February 6, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Other Study ID Numbers: MOR107-C001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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