First in Human Single Ascending Dose Study of MOR107

• ClinicalTrials.gov Identifier: NCT03067363
• Recruitment Status: Terminated
• First Posted: March 1, 2017
• Last Update Posted: February 7, 2018
• Sponsor: Alan Richardson
• Collaborator: Quotient Clinical
• Information provided by (Responsible Party): Alan Richardson, LanthioPep BV

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Safety	Drug: MOR107; Drug: Placebo; Other: Low sodium diet	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Intervention Model Description: Part 1: single ascending doses Part 2: parallel group
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Basic Science
• Official Title: 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
• Actual Study Start Date: February 16, 2017
• Actual Primary Completion Date: March 23, 2017
• Actual Study Completion Date: March 23, 2017

Arms and Interventions

Arm	Intervention/treatment
Experimental: Part 1, MOR107 Dose level 1; MOR107, single subcutaneous injection	Drug: MOR107; MOR107 solution for injection; Other Name: LP2-3
Experimental: Part 1, MOR107 Dose level 2; MOR107, single subcutaneous injection	Drug: MOR107; MOR107 solution for injection; Other Name: LP2-3
Experimental: Part 1, MOR107 Dose level 3; MOR107, single subcutaneous injection	Drug: MOR107; MOR107 solution for injection; Other Name: LP2-3
Experimental: Part 1, MOR107 Dose level 4; MOR107, single subcutaneous injection	Drug: MOR107; MOR107 solution for injection; Other Name: LP2-3
Experimental: Part 1, MOR107 Dose level 5; MOR107, single subcutaneous injection	Drug: MOR107; MOR107 solution for injection; Other Name: LP2-3
Experimental: Part 1, MOR107 Dose level 6; MOR107, single subcutaneous injection	Drug: MOR107; MOR107 solution for injection; Other Name: LP2-3
Placebo Comparator: Part 1, Placebo; Placebo, single subcutaneous injection	Drug: Placebo; Solution for injection manufactured to match MOR107 solution for injection; Other Name: 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 Name: 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 Name: 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 Name: 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 Name: Placebo (for MOR107); Other: Low sodium diet; Diet designed to restrict sodium intake to 40 mmol/day

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 45 Years (Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

Criteria

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

Contacts and Locations

Locations

United Kingdom

Quotient Clinical

Nottingham, Nottinghamshire, United Kingdom, NG11 6JS

Sponsors and Collaborators

Alan Richardson

Quotient Clinical

Investigators

• Study Director: Axel Mescheder, MD; LanthioPep BV

More Information

• Responsible Party: Alan Richardson, Clinical Project Manager, LanthioPep BV
• ClinicalTrials.gov Identifier: NCT03067363 History of Changes
• Other Study ID Numbers: MOR107-C001
• First Posted: March 1, 2017
• Last Update Posted: February 7, 2018
• Last Verified: February 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No