First in Human Single Ascending Dose Study of MOR107

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Safety

Intervention / Treatment
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* Drug: MOR107
* Drug: Placebo
* Other: Low sodium diet


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Healthy males Age 18 to 45 years of age Body mass index of 18.0 to 32.0 kg/m2 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: Subjects who have received any IMP in a clinical research study within the previous three months Regular alcohol consumption >21 units per week (1 unit = ½ pint beer, 25 mL of 40% spirit or a 125 mL glass of wine) 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 Current smokers of e-cigarettes and nicotine replacement products and those who have smoked these products within the last 12 months Clinically significant abnormal biochemistry, haematology or urinalysis as judged by the investigator Positive drugs of abuse test result Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) results History of psychiatric disorder, cardiovascular, renal, hepatic, chronic respiratory or gastrointestinal disease as judged by the investigator Serious adverse reaction or serious hypersensitivity to any drug or the formulation excipients

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Part 1: single ascending doses Part 2: parallel group
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 |