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Phase 2A Clinical Trial Evaluating the Potential Activity and Safety of hMaxi-K Gene for ED

U

Urovant Sciences

Status and phase

Completed
Phase 2

Conditions

Erectile Dysfunction

Treatments

Drug: Placebo (PBS-20% sucrose)
Drug: hMaxi-K Single Treatment/ 2 escalating dose levels (8000 µg and 16000 µg injection)

Study type

Interventional

Funder types

Other
Industry

Identifiers

NCT02713789
ION04-ED

Details and patient eligibility

About

To evaluate the safety and efficacy of a single intracavernous injection of hMaxi K (8000 µg and 16000 µg) or placebo upon penile rigidity or erection in males with erectile dysfunction longer than six months that is attributable to an underlying, stable medical condition.

Full description

This study is a double-blind, placebo controlled, parallel design, Phase 2A study evaluating the potential activity and safety of a single administration of hMaxi-K (8000 or 16000 µg) or placebo (PBS sucrose 20%) injected into the corpus cavernosum of the penis in men who have been unable to tolerate, do not wish to continue, or have had unsuccessful results with, prior therapy for ED.

The study population is men with erectile dysfunction attributable to an underlying, stable medical condition but who are otherwise in good health. The target population is men with erectile dysfunction and those who have been unable to tolerate, do not wish to continue, or have had unsuccessful results with, prior therapy for ED and with an erectile function domain score of IIEF < 21 at screening and baseline.

Following screening and study drug administration at Week 0 (Visit 2 [V2]), eligible participants will be evaluated at Weeks 1 (V3), 4 (V4), 8 (V5), 12 (V6), and 24 (V7). At each study visit, participants will have a physical examination including examination of the penis (all visits), vital signs, electrocardiogram (ECG) (all visits). Laboratory evaluations including chemistry and hematology will be done at V1, V3, V4, V6, and V7. Urinalysis will be done V1, V2 (prior to dosing), V3, V4, V6, and V7. Endocrine parameters and PTT, PT, sed rate and CRP will be evaluated at V1, V3, and V7. The participant will complete the erectile function domain of the IIEF and Sexual Encounter Profile (SEP) at screening/baseline and at V2, (SEP and IIEF at V2 prior to dosing) V3, V4, V5, V6, and V7. In all participants, plasma specimens will be collected to assay for the presence of hSlo DNA by PCR (V2-V7). These will be kept frozen at -20°C or less at the site for eventual assay by Sponsor.

The primary efficacy outcome measures will include the Erectile Function (EF) domain of the International Index of Erectile Function (IIEF), Sexual Encounter Profile (SEP), Questions 2 and 3 from SEP. The IIEF EF domain has a 30-point total score, where higher scores reflect better erectile function. SEP is a diary in which participants record each sexual attempt made throughout the study. The two questions from the Sexual Encounter Profile (SEP) deal with the ability to achieve vaginal penetration (SEP2), and the ability to maintain an erection long enough for successful intercourse (SEP3). The erectile function domain category of the IIEF will be used to evaluate the change in erectile status from baseline following administration of hMaxi-K. Change from baseline on the six questions of the IIEF's Erectile function domain category at every visit after administration of study drug will be calculated and compared among the two dose and one placebo groups.

Safety will be assessed by analysis of adverse experiences, and abnormal findings on clinical laboratory tests, electrocardiogram, and physical examinations.

6 months per participant (approximately 2 years to enroll all participants)

A total of 35 participants were planned to be enrolled; N=11 on 8000 µg; N=11 on 16000 µg; N=13 on placebo.

Both the safety data and data to assess activity will be presented as means and standard deviations or medians and ranges as appropriate for continuous data, and analyzed using either paired t- or Wilcox on Sign Rank tests for within group changes, and with mixed effects or marginal models to determine differences in trends among the three cohorts over time. Incidence of adverse events will be presented as relative frequencies within groups.

Enrollment

26 patients

Sex

Male

Ages

18 to 80 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

  • Eligible participants must meet the following inclusion criteria:

    1. Signed Informed Consent
    2. Be adult males over 18 years of age diagnosed with erectile dysfunction and whose ED is attributable to an underlying, stable medical condition such as hypertension and atherosclerosis, antihypertensive medication, type I and type II diabetes mellitus, pelvic surgery and pelvic radiation, cerebrovascular accidents (stroke), multiple sclerosis, and Parkinson's disease;
    3. Participants must have been unable to have successful sexual intercourse for 3 months prior to study entry without specific ED therapy such as Vacuum Erection device (VED), ViagraTM (sildenafil), Cialis TM (tadalafil), MuseTM (alprostadil), or intracavernous injection therapy with an erectile function domain score of IIEF<21 at screening and baseline;
    4. Have been unable to tolerate, do not wish to continue, or have had unsuccessful results with, prior therapy for ED, e.g., ViagraTM, intracavernous injection therapy, MuseTM, or VED;
    5. If diabetic, documentation of HgA1c less than or equal to 8.0% prior to enrollment;
    6. If receiving medication for hypertension, documentation of blood pressure has been stable on the same medication for at least 2 months prior to enrollment;
    7. Be heterosexual and in a stable, monogamous relationship of at least six months duration;
    8. Agree to attempt intercourse with their partner at least four times per month while participating in the study;
    9. Agree not to use other treatments for ED while participating in this study;
    10. Have screening laboratory values and ECG that are within the normal range. See exclusion criterion below.
    11. A prior penile prosthetic implant;
    12. Have a normal physical examination of the penis;
    13. If participant had a radical prostatectomy a PSA <0.4 for at least one year documented by 2 measurements during the preceding year;
    14. Be literate, able to give written informed consent, and comply with all study procedures and requirements.

Exclusion criteria

  1. A history of sickle-cell disease, sickle cell trait, or any other medical condition that, in the judgment of the investigator, would contraindicate the administration of study medication or interfere with the study evaluations;

  2. In the judgment of the investigator any condition that would interfere with participation in the study (including geographical inaccessibility), that would contraindicate the administration of study medication or interfere with the study evaluations.

  3. Had within six months prior to enrollment any of the following:

    • Myocardial infarction
    • Cerebrovascular accident
    • Uncontrolled hypertension (systolic >160 or diastolic >100mmHg)
    • Arrhythmia
    • Congestive heart failure (dyspnea on minimal exertion or while supine)
    • Unstable angina (chest pain greater than three times weekly while on therapy)
    • Required treatment with calcium channel, beta-blocker medication, nitrates, or anti-epileptic drugs;
  4. Poorly controlled diabetes mellitus as defined by HgA1c > 8.0 mg% at time of enrollment;

  5. Change in medication for diabetes or hypertension within 2 months of study enrollment;

  6. Gonadal failure (testosterone < 200 ng/dl) not treated with hormone replacement;

  7. History of malignancy except non-melanomatous skin cancers;

  8. A life expectancy of less than 12 months;

  9. An indwelling urethral catheter;

  10. A prior penile prosthetic implant;

  11. Received an investigational drug, investigational therapy, or other form of ED therapy, including approved treatments, within the past 30 days;

  12. Peyronie's disease;

  13. Any screening laboratory values outside of the normal laboratory range as defined by the central laboratory normal ranges and in the judgment of the investigator is considered clinically significant (hepatic biochemical markers [AST, ALT, GGT, alkaline phosphatase, and bilirubin] > twice the upper limit of the normal reference range may be accepted with written consent of the sponsor).

  14. Any clinically significant ECG abnormality

NOTE: Sinus bradycardia of 50-59 bpm is permissible. Other abnormalities that can be normal variants (and considered clinically insignificant) may be permissible. However, participants with such abnormalities cannot be randomized without review of their medical history and prior written approval of the sponsor (or designee).

Trial design

Primary purpose

Other

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Double Blind

26 participants in 2 patient groups, including a placebo group

hMaxi-K
Active Comparator group
Description:
Single Treatment/ two escalating dose levels (8000 µg and 16,000 µg injection). In each dose level, 11 participants will receive hMaxi-K and 6 will receive placebo (only one injection per each participant)
Treatment:
Drug: hMaxi-K Single Treatment/ 2 escalating dose levels (8000 µg and 16000 µg injection)
Placebo (PBS-20% sucrose)
Placebo Comparator group
Description:
PBS-20% sucrose administered during two single treatment dose levels (8000 µg and 16000 µg) by injection (only one injection per each participant)
Treatment:
Drug: Placebo (PBS-20% sucrose)

Trial documents
2

Trial contacts and locations

1

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Data sourced from clinicaltrials.gov

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